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Hangzhou Think Chemical Co. Ltd

Certificate of Analysis Product Name Ivabradine hydrochloride CAS Registry No. 148849-67-6 Specification No. IH17-02

Supply Ivabradine HCl API and Intermediate factory

Cas:148849-67-6

Min.Order:1 Kilogram

Negotiable

Type:Other

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Dayang Chem (Hangzhou) Co.,Ltd.

As a leading manufacturer and supplier of chemicals in China, DayangChem not only supply popular chemicals, but also DayangChem’s R&D center offer custom synthesis services. DayangChem can provide different quantities of custom synthesis

Ivabradine hydrochloride

Cas:148849-67-6

Min.Order:1 Kilogram

FOB Price: $3.0

Type:Lab/Research institutions

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Simagchem Corporation

Welcome to Simagchem, your partner in China as a premier supply of bulk specialty chemicals for industry and life science. We introduce experienced quality product and exceptional JIT service with instant market intelligence in China to benefit our

High quality Ivabradine Hydrochloride supplier in China

Cas:148849-67-6

Min.Order:0 Metric Ton

Negotiable

Type:Manufacturers

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Wuhan Fortuna Chemical Co.,Ltd

Unique advantages for Ivabradine hydrochloride Cas 148849-67-6 Guaranteed purity High quality & competitive price Quality control Fast feedback Prompt shipment Appearance:White to off-white powder Storage:-20°C Freezer Package:10g,100

Factory supply Ivabradine hydrochloride Cas 148849-67-6 with high quality and fast delivery

Cas:148849-67-6

Min.Order:10 Gram

FOB Price: $10.0 / 15.0

Type:Trading Company

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Henan Allgreen Chemical Co.,Ltd

high quality Appearance:White or off-white Solid Storage:Sealed, dry, microtherm , avoid light and smell. Package:According to the demand of customer Application:Organic synthesis Transportation:by air or by sea Port:shanghai

Ivabradine hydrochloride

Cas:148849-67-6

Min.Order:1 Kilogram

Negotiable

Type:Manufacturers

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Hangzhou JINLAN Pharm-Drugs Technology Co., Ltd

We can provide GMP validation service that complies with SFDA, FDA, WHO and EU EMPA.Excellent registration team could help us easlily to register our products in different countries.If you and your customer are interested in some products or need C

ivabradine hydrochloride manufacturer with low price

Cas:148849-67-6

Min.Order:1 Gram

Negotiable

Type:Manufacturers

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Ality Chemical Corporation

The above product is Ality Chemical's strong item with best price, good quality and fast supply. Ality Chemical has been focusing on the research and production of this field for over 14 years. At the same time, we are always committed to providi

Factory Supply Ivabradine Hydrochloride

Cas:148849-67-6

Min.Order:1

Negotiable

Type:Other

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Xi'an Xszo Chem Co., Ltd.

1. Factory price and high quality must be guaranteed, base on 8 years of production and R&D experience2. Free samples will be provided,ensure specifications and quality are right for customer3. Customers will receive the most professional technical s

Factory Price API 99% Ivabradine hydrochloride 148849-67-6 GMP Manufacturer

Cas:148849-67-6

Min.Order:1 Gram

FOB Price: $0.1

Type:Manufacturers

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Anhui Dexinjia Biopharm Co., Ltd

As a leading and professional manufacturer of APIs and API intermediates in China,Anhui Dexinjia Biopharm Co., Ltd founded in 2006, Except for the R&D center, our company has built a close cooperation relation with Chinese Academy of Sciences,

Ivabradine hydrochloride/Manufacturer/High quality/Best price/In stock

Cas:148849-67-6

Min.Order:1 Gram

FOB Price: $1.0

Type:Manufacturers

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Hebei yanxi chemical co.,LTD.

hebei yanxi chemical co., LTD who registered capital of 10 million yuan, nearly to $2 million, we have a pharmaceutical raw materials factory production of pharmaceutical raw materials, and a reagent r&d center, and we do research and developm

Ivabradine hydrochloride CAS NO.148849-67-6

Cas:148849-67-6

Min.Order:1 Metric Ton

FOB Price: $1.0 / 3.0

Type:Trading Company

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Chemwill Asia Co., Ltd.

Our main production base is located in Xuzhou industry park. We are certified both to the ISO 9001 and ISO 14001 Standards, have a safety management system in place.Our R&D team masters core technology for process-design of target building block

ivabradine hydrochloride

Cas:148849-67-6

Min.Order:5 Kiloliter

FOB Price: $1.2 / 5.0

Type:Manufacturers

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Henan Tianfu Chemical Co., Ltd.

Product Name: Ivabradine hydrochloride Synonyms: 3-[3-[[[(7S)-3,4-Dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl]methyl]methylamino]propyl]-1,3,4,5-tetrahydro-7,8-dimethoxy-2H-3-benzazepin-2-one Hydrochloride;Corlentor;Procoralan;S-16257;(7,8-Dimeth

148849-67-6 Ivabradine hydrochloride

Cas:148849-67-6

Min.Order:1 Kilogram

FOB Price: $470.0

Type:Lab/Research institutions

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LIDE PHARMACEUTICALS LIMITED

Advantage : LIDE PHARMACEUTICALS LTD. is a mid-small manufacturing-type enterprise, engaged in pharmaceutical intermediates of R&D, custom-made and production, and also involving trading chemicals for export. We have established the R&amp

Ivabradine hydrochloride/ LIDE PHARMA- Factory supply / Best price

Cas:148849-67-6

Min.Order:1 Gram

Negotiable

Type:Lab/Research institutions

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Hebei Nengqian Chemical Import and Export Co., LTD

Our advantages: 1. All inquiries will be replied within 12 hours. 2. Dedication to quality, supply & service. 3. Strictly on selecting raw materials. 4. Reasonable & competitive price, fast lead time. 5. Sample is available for your eva

Ivabradine hydrochloride

Cas:148849-67-6

Min.Order:1 Kilogram

FOB Price: $9.0 / 99.0

Type:Trading Company

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Zhuozhou Wenxi import and Export Co., Ltd

WITH US,YOUR MONEY IN SAFE,YOUR BUSINESS IN SAFE 1)Quick Response Within 12 hours; 2)Quality Guarantee: All products are strictly tested by our QC, confirmed by QA and approved by third party lab in China, USA, Canada, Germany, UK, Italy, France et

New production CAS 148849-67-6 with best quality

Cas:148849-67-6

Min.Order:1 Kilogram

FOB Price: $139.0 / 210.0

Type:Trading Company

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Wuhan Han Sheng New Material Technology Co.,Ltd

Our Advantage: high quality with competitive price High quality standard: BP/USP/EP Enterprise standard All purity customized Fast and safe delivery We have reliable forwarder who can help us deliver our goods more fast and safe. We

Ivabradine hydrochloride CAS NO.148849-67-6

Cas:148849-67-6

Min.Order:10 Kilogram

Negotiable

Type:Trading Company

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Henan Sinotech Import&Export Corporation

Name Ivabradine hydrochloride Synonyms 3-[3-[[(8S)-3,4-Dimethoxy-8-bicyclo[4.2.0]octa-1,3,5-trienyl]methyl-methylamino]propyl]-7,8-dimethoxy-2,5-dihydro-1H-3-benzazepin-4-one hydrochloride Molecular Structur

Ivabradine hydrochloride CAS:148849-67-6

Cas:148849-67-6

Min.Order:1 Kilogram

FOB Price: $1.0

Type:Other

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Hubei Langyou International Trading Co., Ltd

Advantages: Hubei XinRunde Chemical Co., Ltd is a renowned pharmaceutical manufacturer. We can offer high quality products at competitive price in quick delivery with 100% custom pass guaranteed. Never stop striving to offer our best serv

Ivabradine Hydrochloride Manufacturer For Angina Pectoris

Cas:148849-67-6

Min.Order:10 Gram

Negotiable

Type:Other

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HANWAYS CHEMPHARM CO.,LIMITED

We are concentrating on APIs and pharmaceutical intermediates. With in depth knowledge and understanding in this industry, we are indulged in supplying a wide assortments of Ivabradine hydrochloride from Wuhan, Hubei, China.

Ivabradine hydrochloride

Cas:148849-67-6

Min.Order:100 Gram

FOB Price: $1.0

Type:Trading Company

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Shanghai Upbio Tech Co.,Ltd

1.No Less 8 years exporting experience. Clients can 100% received goods 2.Lower Price with higher quality 3,Free sample 4,We are sincerely responsible for the "product quality" and "After Service" Upbio is Specialized

Hangzhou Huarong Pharm Co., Ltd.

Hangzhou Huarong Pharm Co., Ltd. established since 2009 , has been always focusing on supplying products and services to our clients in the field of small molecule drug. Huarong Pharm has built platforms for the research, development and manufac

Ivabradine hydrochloride

Cas:148849-67-6

Min.Order:1 Kilogram

FOB Price: $1.0 / 2.0

Type:Lab/Research institutions

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Hangzhou Fonlynn Health Technology Co., Ltd.

Packing: According to customer requirements Delivery time: In stock or depands Port of shipment: Ningbo/Shanghai/Qingdao OEM/ODM:Welcome Sample:We can offer our existing samples at once Appearance:white powder/ Refer to COA Storage:Refer to COA

148849-67-6 cas 99% BP USP Ivabradine HCl

Cas:148849-67-6

Min.Order:1 Kilogram

Negotiable

Type:Trading Company

inquiry

Qingdao Beluga Import and Export Co., LTD

Beluga chemical professional supply High quality Ivabradine hydrochloride manufacturer 1. Beluga Chemical has a professional RESEARCH and development team and strong technical force to ensure technical support and research capabilities. 2. Made i

High quality Ivabradine hydrochloride manufacturer

Cas:148849-67-6

Min.Order:1 Gram

Negotiable

Type:Lab/Research institutions

inquiry

Shandong Hanjiang Chemical Co., Ltd.

Hello, dear friend! I'm Hansen and Allen from China. Welcome to my lookchem mall! The following is a brief introduction of our company's products and services. If you are interested in our products, please contact us by emai

Ivabradine hydrochloride

Cas:148849-67-6

Min.Order:1 Kilogram

Negotiable

Type:Lab/Research institutions

inquiry

Henan Wentao Chemical Product Co., Ltd.

Henan Wentao Chemical Product Co.,Ltd is Located in Zhengzhou High-tech Development Zone with import and export license, We passed ISO 9001:2008 as well, Henan Wentao has developed more than 1000 compounds, which are widely used in the fields of prod

Hebei Mojin Biotechnology Co.,Ltd

Hebei Mojin Biotechnology Co., Ltd,Our business covers more than 30 countries, most of the big customers come from Europe, America and other countries in the world, we can guarantee the quality and price. In recent decades, with the efforts of all em

Ivabradine Hydrochloride Powder CAS 148849-67-6

Cas:148849-67-6

Min.Order:1 Gram

FOB Price: $50000.0

Type:Trading Company

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Triumph International Development Limilted

Appearance:white powder without visible impurities Storage:Store in a cool,dry place and keep away from direct strong light Package:As customer request Application:Used for research and industrial manufacture. Transportation:By

Ivabradine hydrochloride

Cas:148849-67-6

Min.Order:100 Gram

Negotiable

Type:Lab/Research institutions

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Afine Chemicals Limited

Our Services 1. New Molecules R&D 2. Own test center HPLC NMR GC LC-MS 3. API and Intermediates from China reputed manufacturers 4. Documents support COA MOA MSDS DMF open part Our advantages 1. Government awarded company. Top 100 enter

Ivabradine hydrochloride

Cas:148849-67-6

Min.Order:1 Kilogram

Negotiable

Type:Lab/Research institutions

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Wuhan Zenuo Biological Medicine Technology Co Ltd

Product Name: Ivabradine hydrochloride Synonyms: 3-[3-[[[(7S)-3,4-Dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl]methyl]methylamino]propyl]-1,3,4,5-tetrahydro-7,8-dimethoxy-2H-3-benzazepin-2-one Hydrochloride;Corlentor;Procoralan;S-16257;(7,8-Dime

Ivabradine hydrochloride 99% Manufactuered in China best quality

Cas:148849-67-6

Min.Order:100 Gram

Negotiable

Type:Lab/Research institutions

inquiry

Taizhou Crene Biotechnology co.ltd

Our company provides one-stop services of research - development - production for a variety of special prouducts. Not only do we make effective use of our strong technological strength, but also establish of cooperative relations with several well-

Ivabradine hydrochloride 148849-67-6

Cas:148849-67-6

Min.Order:1 Gram

Negotiable

Type:Lab/Research institutions

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Synthetic route

3-{3-[{[(7S)-3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl]methyl}-(methyl)amino]propyl}-7,8-dimethoxy-1,3-dihydro-2H-3-benzazepin-2-one
1086026-31-4

3-{3-[{[(7S)-3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl]methyl}-(methyl)amino]propyl}-7,8-dimethoxy-1,3-dihydro-2H-3-benzazepin-2-one

ivabradine hydrochloride
148849-67-6

ivabradine hydrochloride

Conditions
ConditionsYield
Stage #1: 3-{3-[{[(7S)-3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl]methyl}-(methyl)amino]propyl}-7,8-dimethoxy-1,3-dihydro-2H-3-benzazepin-2-one With palladium 10% on activated carbon; hydrogen; acetic acid at 15 - 25℃; for 23h;
Stage #2: With hydrogenchloride In ethyl acetate; isopropyl alcohol at 0 - 10℃; for 1h;
93.5%
Stage #1: 3-{3-[{[(7S)-3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl]methyl}-(methyl)amino]propyl}-7,8-dimethoxy-1,3-dihydro-2H-3-benzazepin-2-one With palladium 10% on activated carbon; hydrogen; ammonium formate In methanol at 25 - 30℃;
Stage #2: With hydrogenchloride In dichloromethane
78%
With hydrogenchloride; hydrogen; palladium 10% on activated carbon In water at 45℃; under 7500.75 Torr; for 6h;
Multi-step reaction with 2 steps
1: hydrogenchloride / acetonitrile / 20 - 25 °C
2: 5%-palladium/activated carbon; hydrogen / methanol / 18 h / 30 - 35 °C / 3000.3 - 3750.38 Torr / Autoclave
View Scheme
Stage #1: 3-{3-[{[(7S)-3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl]methyl}-(methyl)amino]propyl}-7,8-dimethoxy-1,3-dihydro-2H-3-benzazepin-2-one With palladium 10% on activated carbon; hydrogen In methanol at 25 - 30℃; under 5250.53 - 6000.6 Torr;
Stage #2: With hydrogenchloride In dichloromethane; water
24.48 g
3-(2-[1,3]-dioxolan-2-yl-ethyl)-7,8-dimethoxy-1,3-dihydro-2H-3-benzazepin-2-one

3-(2-[1,3]-dioxolan-2-yl-ethyl)-7,8-dimethoxy-1,3-dihydro-2H-3-benzazepin-2-one

1-[(7S)-3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl]-N-methylmethanamine hydrochloride
866783-13-3

1-[(7S)-3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl]-N-methylmethanamine hydrochloride

ivabradine hydrochloride
148849-67-6

ivabradine hydrochloride

Conditions
ConditionsYield
Stage #1: 3-(2-[1,3]-dioxolan-2-yl-ethyl)-7,8-dimethoxy-1,3-dihydro-2H-3-benzazepin-2-one With hydrogen; palladium on activated charcoal In ethanol at 55℃; under 3750.38 Torr;
Stage #2: 1-[(7S)-3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl]-N-methylmethanamine hydrochloride In ethanol; water at 20 - 85℃; under 22502.3 Torr;
85%
Stage #1: 3-(2-[1,3]-dioxolan-2-yl-ethyl)-7,8-dimethoxy-1,3-dihydro-2H-3-benzazepin-2-one With palladium on activated charcoal; hydrogen In ethanol at 55℃; under 3750.38 Torr; Autoclave; Large scale;
Stage #2: 1-[(7S)-3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl]-N-methylmethanamine hydrochloride With palladium on activated charcoal; hydrogen In ethanol; water at 85℃; under 22502.3 Torr; Autoclave; Large scale;
85%
Stage #1: 3-(2-[1,3]-dioxolan-2-yl-ethyl)-7,8-dimethoxy-1,3-dihydro-2H-3-benzazepin-2-one With palladium on activated charcoal; hydrogen In ethanol at 20 - 55℃; under 3750380 Torr; Autoclave; Inert atmosphere;
Stage #2: 1-[(7S)-3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl]-N-methylmethanamine hydrochloride In ethanol; water at 20 - 85℃; under 63756400 Torr; Inert atmosphere;
85%
3-[2-(1,3-Dioxolan-2-yl)-ethyl]-7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one

3-[2-(1,3-Dioxolan-2-yl)-ethyl]-7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one

1-[(7S)-3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl]-N-methylmethanamine hydrochloride
866783-13-3

1-[(7S)-3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl]-N-methylmethanamine hydrochloride

ivabradine hydrochloride
148849-67-6

ivabradine hydrochloride

Conditions
ConditionsYield
With palladium on activated charcoal; hydrogen In ethanol; water at 85℃; under 22502.3 Torr; Autoclave;85%
ivabradine
155974-00-8

ivabradine

ivabradine hydrochloride
148849-67-6

ivabradine hydrochloride

Conditions
ConditionsYield
With hydrogenchloride In water; acetonitrile at 20℃; pH=2;81%
With hydrogenchloride In acetonitrile at 60℃; pH=2 - 3;80.1%
With hydrogenchloride In diethyl ether; acetonitrile Product distribution / selectivity;78%
3-[3-({[(7S)-3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl]methyl}(methyl)amino)propyl]-7,8-dimethoxy-1,3-dihydro-2H-3-benzazepin-2-one hydrochloride
1086026-38-1

3-[3-({[(7S)-3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl]methyl}(methyl)amino)propyl]-7,8-dimethoxy-1,3-dihydro-2H-3-benzazepin-2-one hydrochloride

ivabradine hydrochloride
148849-67-6

ivabradine hydrochloride

Conditions
ConditionsYield
With 5%-palladium/activated carbon; hydrogen In methanol at 30 - 35℃; under 3000.3 - 3750.38 Torr; for 18h; Autoclave;80%
1-[(7S)-3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl]-N-methylmethanamine hydrochloride
866783-13-3

1-[(7S)-3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl]-N-methylmethanamine hydrochloride

ivabradine hydrochloride
148849-67-6

ivabradine hydrochloride

Conditions
ConditionsYield
Multi-step reaction with 3 steps
1.1: potassium carbonate; sodium iodide / 1-methyl-pyrrolidin-2-one / 20 - 60 °C / Inert atmosphere
1.2: 2 h / 20 °C
2.1: potassium carbonate / water / 0.08 h
2.2: Inert atmosphere
3.1: hydrogenchloride; hydrogen / palladium 10% on activated carbon / water / 6 h / 45 °C / 7500.75 Torr
View Scheme
Multi-step reaction with 2 steps
1: triethylamine / acetonitrile / 12 h / 20 °C
2: hydrogenchloride; pyrographite / acetonitrile / 0.17 h / 70 °C / pH 2 - 3
View Scheme
3,4-dimethoxy-bicyclo[4.2.0]octa-1,3,5-triene-7-carbonitrile
35202-54-1

3,4-dimethoxy-bicyclo[4.2.0]octa-1,3,5-triene-7-carbonitrile

ivabradine hydrochloride
148849-67-6

ivabradine hydrochloride

Conditions
ConditionsYield
Multi-step reaction with 9 steps
1.1: potassium hydroxide; water / 4 h / Reflux
1.2: 20 °C
2.1: ethyl acetate / 1.25 h / 0 °C / Reflux
3.1: hydrogenchloride / dichloromethane; water / 0.08 h
4.1: oxalyl dichloride / N,N-dimethyl-formamide / dichloromethane / 15 - 25 °C
5.1: dichloromethane; water / 0 - 10 °C
6.1: borane-THF / tetrahydrofuran / 20 - 50 °C
6.2: 0.25 h / 0 - 5 °C
6.3: 2.5 h / 0 °C / Reflux
7.1: potassium carbonate; sodium iodide / 1-methyl-pyrrolidin-2-one / 20 - 60 °C / Inert atmosphere
7.2: 2 h / 20 °C
8.1: potassium carbonate / water / 0.08 h
8.2: Inert atmosphere
9.1: hydrogenchloride; hydrogen / palladium 10% on activated carbon / water / 6 h / 45 °C / 7500.75 Torr
View Scheme
Multi-step reaction with 9 steps
1.1: potassium hydroxide; water / 4 h / Reflux
1.2: 20 °C
2.1: acetone / 0.5 h / Reflux; Cooling
3.1: hydrogenchloride / ethyl acetate; water / 0.08 h / pH 3
4.1: oxalyl dichloride / N,N-dimethyl-formamide / dichloromethane / 15 - 25 °C
5.1: dichloromethane; water / 0 - 10 °C
6.1: borane-THF / tetrahydrofuran / 20 - 50 °C
6.2: 0.25 h / 0 - 5 °C
6.3: 2.5 h / 0 °C / Reflux
7.1: potassium carbonate; sodium iodide / 1-methyl-pyrrolidin-2-one / 20 - 60 °C / Inert atmosphere
7.2: 2 h / 20 °C
8.1: potassium carbonate / water / 0.08 h
8.2: Inert atmosphere
9.1: hydrogenchloride; hydrogen / palladium 10% on activated carbon / water / 6 h / 45 °C / 7500.75 Torr
View Scheme
Multi-step reaction with 9 steps
1.1: potassium hydroxide; water / 4 h / Reflux
1.2: 20 °C
2.1: ethyl acetate / 1 h / 18 °C / Heating
3.1: hydrogenchloride / dichloromethane; water / 0.33 h
4.1: oxalyl dichloride / N,N-dimethyl-formamide / dichloromethane / 15 - 25 °C
5.1: dichloromethane; water / 0 - 10 °C
6.1: borane-THF / tetrahydrofuran / 20 - 50 °C
6.2: 0.25 h / 0 - 5 °C
6.3: 2.5 h / 0 °C / Reflux
7.1: potassium carbonate; sodium iodide / 1-methyl-pyrrolidin-2-one / 20 - 60 °C / Inert atmosphere
7.2: 2 h / 20 °C
8.1: potassium carbonate / water / 0.08 h
8.2: Inert atmosphere
9.1: hydrogenchloride; hydrogen / palladium 10% on activated carbon / water / 6 h / 45 °C / 7500.75 Torr
View Scheme
(R,S)-4,5-dimethoxy-1,2-dihydrocyclobutabenzene-1-carboxylic acid
41234-23-5

(R,S)-4,5-dimethoxy-1,2-dihydrocyclobutabenzene-1-carboxylic acid

ivabradine hydrochloride
148849-67-6

ivabradine hydrochloride

Conditions
ConditionsYield
Multi-step reaction with 8 steps
1.1: ethyl acetate / 1.25 h / 0 °C / Reflux
2.1: hydrogenchloride / dichloromethane; water / 0.08 h
3.1: oxalyl dichloride / N,N-dimethyl-formamide / dichloromethane / 15 - 25 °C
4.1: dichloromethane; water / 0 - 10 °C
5.1: borane-THF / tetrahydrofuran / 20 - 50 °C
5.2: 0.25 h / 0 - 5 °C
5.3: 2.5 h / 0 °C / Reflux
6.1: potassium carbonate; sodium iodide / 1-methyl-pyrrolidin-2-one / 20 - 60 °C / Inert atmosphere
6.2: 2 h / 20 °C
7.1: potassium carbonate / water / 0.08 h
7.2: Inert atmosphere
8.1: hydrogenchloride; hydrogen / palladium 10% on activated carbon / water / 6 h / 45 °C / 7500.75 Torr
View Scheme
Multi-step reaction with 8 steps
1.1: acetone / 0.5 h / Reflux; Cooling
2.1: hydrogenchloride / ethyl acetate; water / 0.08 h / pH 3
3.1: oxalyl dichloride / N,N-dimethyl-formamide / dichloromethane / 15 - 25 °C
4.1: dichloromethane; water / 0 - 10 °C
5.1: borane-THF / tetrahydrofuran / 20 - 50 °C
5.2: 0.25 h / 0 - 5 °C
5.3: 2.5 h / 0 °C / Reflux
6.1: potassium carbonate; sodium iodide / 1-methyl-pyrrolidin-2-one / 20 - 60 °C / Inert atmosphere
6.2: 2 h / 20 °C
7.1: potassium carbonate / water / 0.08 h
7.2: Inert atmosphere
8.1: hydrogenchloride; hydrogen / palladium 10% on activated carbon / water / 6 h / 45 °C / 7500.75 Torr
View Scheme
Multi-step reaction with 8 steps
1.1: ethyl acetate / 1 h / 18 °C / Heating
2.1: hydrogenchloride / dichloromethane; water / 0.33 h
3.1: oxalyl dichloride / N,N-dimethyl-formamide / dichloromethane / 15 - 25 °C
4.1: dichloromethane; water / 0 - 10 °C
5.1: borane-THF / tetrahydrofuran / 20 - 50 °C
5.2: 0.25 h / 0 - 5 °C
5.3: 2.5 h / 0 °C / Reflux
6.1: potassium carbonate; sodium iodide / 1-methyl-pyrrolidin-2-one / 20 - 60 °C / Inert atmosphere
6.2: 2 h / 20 °C
7.1: potassium carbonate / water / 0.08 h
7.2: Inert atmosphere
8.1: hydrogenchloride; hydrogen / palladium 10% on activated carbon / water / 6 h / 45 °C / 7500.75 Torr
View Scheme
Multi-step reaction with 8 steps
1.1: ethyl acetate / 1 h / 18 °C / Heating
2.1: hydrogenchloride / dichloromethane; water / 0.33 h
3.1: oxalyl dichloride / N,N-dimethyl-formamide / dichloromethane / 15 - 25 °C
4.1: dichloromethane; water / 0 - 10 °C
5.1: borane-THF / tetrahydrofuran / 20 - 50 °C
5.2: 0.25 h / 0 - 5 °C
5.3: 2.5 h / 0 °C / Reflux
6.1: potassium carbonate; sodium iodide / 1-methyl-pyrrolidin-2-one / 20 - 60 °C / Inert atmosphere
6.2: 2 h / 20 °C
7.1: potassium carbonate / water / 0.08 h
7.2: Inert atmosphere
8.1: hydrogenchloride; hydrogen / palladium 10% on activated carbon / water / 6 h / 45 °C / 7500.75 Torr
View Scheme
Multi-step reaction with 8 steps
1.1: ethyl acetate / Heating
2.1: hydrogenchloride / dichloromethane; water / 0.33 h
3.1: oxalyl dichloride / N,N-dimethyl-formamide / dichloromethane / 15 - 25 °C
4.1: dichloromethane; water / 0 - 10 °C
5.1: borane-THF / tetrahydrofuran / 20 - 50 °C
5.2: 0.25 h / 0 - 5 °C
5.3: 2.5 h / 0 °C / Reflux
6.1: potassium carbonate; sodium iodide / 1-methyl-pyrrolidin-2-one / 20 - 60 °C / Inert atmosphere
6.2: 2 h / 20 °C
7.1: potassium carbonate / water / 0.08 h
7.2: Inert atmosphere
8.1: hydrogenchloride; hydrogen / palladium 10% on activated carbon / water / 6 h / 45 °C / 7500.75 Torr
View Scheme
(S)-3,4-dimethoxy-bicyclo[4.2.0]octa-1,3,5-triene-7-carboxylic acid (+)-cinchonine

(S)-3,4-dimethoxy-bicyclo[4.2.0]octa-1,3,5-triene-7-carboxylic acid (+)-cinchonine

ivabradine hydrochloride
148849-67-6

ivabradine hydrochloride

Conditions
ConditionsYield
Multi-step reaction with 7 steps
1.1: hydrogenchloride / dichloromethane; water / 0.08 h
2.1: oxalyl dichloride / N,N-dimethyl-formamide / dichloromethane / 15 - 25 °C
3.1: dichloromethane; water / 0 - 10 °C
4.1: borane-THF / tetrahydrofuran / 20 - 50 °C
4.2: 0.25 h / 0 - 5 °C
4.3: 2.5 h / 0 °C / Reflux
5.1: potassium carbonate; sodium iodide / 1-methyl-pyrrolidin-2-one / 20 - 60 °C / Inert atmosphere
5.2: 2 h / 20 °C
6.1: potassium carbonate / water / 0.08 h
6.2: Inert atmosphere
7.1: hydrogenchloride; hydrogen / palladium 10% on activated carbon / water / 6 h / 45 °C / 7500.75 Torr
View Scheme
(7S)-3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-triene-7-carboxylic acid
1220993-44-1

(7S)-3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-triene-7-carboxylic acid

ivabradine hydrochloride
148849-67-6

ivabradine hydrochloride

Conditions
ConditionsYield
Multi-step reaction with 6 steps
1.1: oxalyl dichloride / N,N-dimethyl-formamide / dichloromethane / 15 - 25 °C
2.1: dichloromethane; water / 0 - 10 °C
3.1: borane-THF / tetrahydrofuran / 20 - 50 °C
3.2: 0.25 h / 0 - 5 °C
3.3: 2.5 h / 0 °C / Reflux
4.1: potassium carbonate; sodium iodide / 1-methyl-pyrrolidin-2-one / 20 - 60 °C / Inert atmosphere
4.2: 2 h / 20 °C
5.1: potassium carbonate / water / 0.08 h
5.2: Inert atmosphere
6.1: hydrogenchloride; hydrogen / palladium 10% on activated carbon / water / 6 h / 45 °C / 7500.75 Torr
View Scheme
Multi-step reaction with 3 steps
1.1: chloroformic acid ethyl ester; triethylamine / tetrahydrofuran / 20 °C
1.2: 20 °C
2.1: borane-THF / tetrahydrofuran / 20 °C
2.2: 4 h
3.1: hydrogen; palladium on activated charcoal / ethanol / 55 °C / 3750.38 Torr / Autoclave; Large scale
3.2: 85 °C / 22502.3 Torr / Autoclave; Large scale
View Scheme
(S)-3,4-dimethoxy-bicyclo[4.2.0]octa-1.3,5-triene-7-carboxylic acid (S)-(-)-1-(naphthyl)-ethylamine
1346558-07-3

(S)-3,4-dimethoxy-bicyclo[4.2.0]octa-1.3,5-triene-7-carboxylic acid (S)-(-)-1-(naphthyl)-ethylamine

ivabradine hydrochloride
148849-67-6

ivabradine hydrochloride

Conditions
ConditionsYield
Multi-step reaction with 7 steps
1.1: hydrogenchloride / dichloromethane; water / 0.33 h
2.1: oxalyl dichloride / N,N-dimethyl-formamide / dichloromethane / 15 - 25 °C
3.1: dichloromethane; water / 0 - 10 °C
4.1: borane-THF / tetrahydrofuran / 20 - 50 °C
4.2: 0.25 h / 0 - 5 °C
4.3: 2.5 h / 0 °C / Reflux
5.1: potassium carbonate; sodium iodide / 1-methyl-pyrrolidin-2-one / 20 - 60 °C / Inert atmosphere
5.2: 2 h / 20 °C
6.1: potassium carbonate / water / 0.08 h
6.2: Inert atmosphere
7.1: hydrogenchloride; hydrogen / palladium 10% on activated carbon / water / 6 h / 45 °C / 7500.75 Torr
View Scheme
3,4-dimethoxy-bicyclo[4.2.0]octa-1.3,5-triene-7-carboxylic acid (S)-(-)-1-(naphthyl)-ethylamine

3,4-dimethoxy-bicyclo[4.2.0]octa-1.3,5-triene-7-carboxylic acid (S)-(-)-1-(naphthyl)-ethylamine

ivabradine hydrochloride
148849-67-6

ivabradine hydrochloride

Conditions
ConditionsYield
Multi-step reaction with 7 steps
1.1: hydrogenchloride / dichloromethane; water / 0.33 h
2.1: oxalyl dichloride / N,N-dimethyl-formamide / dichloromethane / 15 - 25 °C
3.1: dichloromethane; water / 0 - 10 °C
4.1: borane-THF / tetrahydrofuran / 20 - 50 °C
4.2: 0.25 h / 0 - 5 °C
4.3: 2.5 h / 0 °C / Reflux
5.1: potassium carbonate; sodium iodide / 1-methyl-pyrrolidin-2-one / 20 - 60 °C / Inert atmosphere
5.2: 2 h / 20 °C
6.1: potassium carbonate / water / 0.08 h
6.2: Inert atmosphere
7.1: hydrogenchloride; hydrogen / palladium 10% on activated carbon / water / 6 h / 45 °C / 7500.75 Torr
View Scheme
Multi-step reaction with 10 steps
1.1: hydrogenchloride / dichloromethane; water / 0.33 h
2.1: potassium hydroxide / water / 4 h
2.2: 0.5 h / Cooling with ice-water bath
3.1: acetone / 0.5 h / Reflux; Cooling
4.1: hydrogenchloride / ethyl acetate; water / 0.08 h / pH 3
5.1: oxalyl dichloride / N,N-dimethyl-formamide / dichloromethane / 15 - 25 °C
6.1: dichloromethane; water / 0 - 10 °C
7.1: borane-THF / tetrahydrofuran / 20 - 50 °C
7.2: 0.25 h / 0 - 5 °C
7.3: 2.5 h / 0 °C / Reflux
8.1: potassium carbonate; sodium iodide / 1-methyl-pyrrolidin-2-one / 20 - 60 °C / Inert atmosphere
8.2: 2 h / 20 °C
9.1: potassium carbonate / water / 0.08 h
9.2: Inert atmosphere
10.1: hydrogenchloride; hydrogen / palladium 10% on activated carbon / water / 6 h / 45 °C / 7500.75 Torr
View Scheme
Multi-step reaction with 10 steps
1.1: hydrogenchloride / dichloromethane; water / 0.33 h
2.1: potassium hydroxide / water / 4 h
2.2: 0.5 h / Cooling with ice-water bath
3.1: ethyl acetate / 1.25 h / 0 °C / Reflux
4.1: hydrogenchloride / dichloromethane; water / 0.08 h
5.1: oxalyl dichloride / N,N-dimethyl-formamide / dichloromethane / 15 - 25 °C
6.1: dichloromethane; water / 0 - 10 °C
7.1: borane-THF / tetrahydrofuran / 20 - 50 °C
7.2: 0.25 h / 0 - 5 °C
7.3: 2.5 h / 0 °C / Reflux
8.1: potassium carbonate; sodium iodide / 1-methyl-pyrrolidin-2-one / 20 - 60 °C / Inert atmosphere
8.2: 2 h / 20 °C
9.1: potassium carbonate / water / 0.08 h
9.2: Inert atmosphere
10.1: hydrogenchloride; hydrogen / palladium 10% on activated carbon / water / 6 h / 45 °C / 7500.75 Torr
View Scheme
Multi-step reaction with 10 steps
1.1: hydrogenchloride / dichloromethane; water / 0.33 h
2.1: potassium hydroxide / water / 4 h
2.2: 0.5 h / Cooling with ice-water bath
3.1: ethyl acetate / Heating
4.1: hydrogenchloride / dichloromethane; water / 0.33 h
5.1: oxalyl dichloride / N,N-dimethyl-formamide / dichloromethane / 15 - 25 °C
6.1: dichloromethane; water / 0 - 10 °C
7.1: borane-THF / tetrahydrofuran / 20 - 50 °C
7.2: 0.25 h / 0 - 5 °C
7.3: 2.5 h / 0 °C / Reflux
8.1: potassium carbonate; sodium iodide / 1-methyl-pyrrolidin-2-one / 20 - 60 °C / Inert atmosphere
8.2: 2 h / 20 °C
9.1: potassium carbonate / water / 0.08 h
9.2: Inert atmosphere
10.1: hydrogenchloride; hydrogen / palladium 10% on activated carbon / water / 6 h / 45 °C / 7500.75 Torr
View Scheme
(R)-4,5-dimethoxy-1,2-dihydrocyclobutabenzene-1-carboxylic acid
1220993-48-5

(R)-4,5-dimethoxy-1,2-dihydrocyclobutabenzene-1-carboxylic acid

ivabradine hydrochloride
148849-67-6

ivabradine hydrochloride

Conditions
ConditionsYield
Multi-step reaction with 9 steps
1.1: potassium hydroxide / water / 4 h
1.2: 0.5 h / Cooling with ice-water bath
2.1: ethyl acetate / 1.25 h / 0 °C / Reflux
3.1: hydrogenchloride / dichloromethane; water / 0.08 h
4.1: oxalyl dichloride / N,N-dimethyl-formamide / dichloromethane / 15 - 25 °C
5.1: dichloromethane; water / 0 - 10 °C
6.1: borane-THF / tetrahydrofuran / 20 - 50 °C
6.2: 0.25 h / 0 - 5 °C
6.3: 2.5 h / 0 °C / Reflux
7.1: potassium carbonate; sodium iodide / 1-methyl-pyrrolidin-2-one / 20 - 60 °C / Inert atmosphere
7.2: 2 h / 20 °C
8.1: potassium carbonate / water / 0.08 h
8.2: Inert atmosphere
9.1: hydrogenchloride; hydrogen / palladium 10% on activated carbon / water / 6 h / 45 °C / 7500.75 Torr
View Scheme
Multi-step reaction with 9 steps
1.1: potassium hydroxide / water / 4 h
1.2: 0.5 h / Cooling with ice-water bath
2.1: acetone / 0.5 h / Reflux; Cooling
3.1: hydrogenchloride / ethyl acetate; water / 0.08 h / pH 3
4.1: oxalyl dichloride / N,N-dimethyl-formamide / dichloromethane / 15 - 25 °C
5.1: dichloromethane; water / 0 - 10 °C
6.1: borane-THF / tetrahydrofuran / 20 - 50 °C
6.2: 0.25 h / 0 - 5 °C
6.3: 2.5 h / 0 °C / Reflux
7.1: potassium carbonate; sodium iodide / 1-methyl-pyrrolidin-2-one / 20 - 60 °C / Inert atmosphere
7.2: 2 h / 20 °C
8.1: potassium carbonate / water / 0.08 h
8.2: Inert atmosphere
9.1: hydrogenchloride; hydrogen / palladium 10% on activated carbon / water / 6 h / 45 °C / 7500.75 Torr
View Scheme
Multi-step reaction with 9 steps
1.1: potassium hydroxide / water / 4 h
1.2: 0.5 h / Cooling with ice-water bath
2.1: ethyl acetate / 1 h / 18 °C / Heating
3.1: hydrogenchloride / dichloromethane; water / 0.33 h
4.1: oxalyl dichloride / N,N-dimethyl-formamide / dichloromethane / 15 - 25 °C
5.1: dichloromethane; water / 0 - 10 °C
6.1: borane-THF / tetrahydrofuran / 20 - 50 °C
6.2: 0.25 h / 0 - 5 °C
6.3: 2.5 h / 0 °C / Reflux
7.1: potassium carbonate; sodium iodide / 1-methyl-pyrrolidin-2-one / 20 - 60 °C / Inert atmosphere
7.2: 2 h / 20 °C
8.1: potassium carbonate / water / 0.08 h
8.2: Inert atmosphere
9.1: hydrogenchloride; hydrogen / palladium 10% on activated carbon / water / 6 h / 45 °C / 7500.75 Torr
View Scheme
Multi-step reaction with 9 steps
1.1: potassium hydroxide / water / 4 h
1.2: 0.5 h / Cooling with ice-water bath
2.1: ethyl acetate / 1 h / 18 °C / Heating
3.1: hydrogenchloride / dichloromethane; water / 0.33 h
4.1: oxalyl dichloride / N,N-dimethyl-formamide / dichloromethane / 15 - 25 °C
5.1: dichloromethane; water / 0 - 10 °C
6.1: borane-THF / tetrahydrofuran / 20 - 50 °C
6.2: 0.25 h / 0 - 5 °C
6.3: 2.5 h / 0 °C / Reflux
7.1: potassium carbonate; sodium iodide / 1-methyl-pyrrolidin-2-one / 20 - 60 °C / Inert atmosphere
7.2: 2 h / 20 °C
8.1: potassium carbonate / water / 0.08 h
8.2: Inert atmosphere
9.1: hydrogenchloride; hydrogen / palladium 10% on activated carbon / water / 6 h / 45 °C / 7500.75 Torr
View Scheme
Multi-step reaction with 9 steps
1.1: potassium hydroxide / water / 4 h
1.2: 0.5 h / Cooling with ice-water bath
2.1: ethyl acetate / Heating
3.1: hydrogenchloride / dichloromethane; water / 0.33 h
4.1: oxalyl dichloride / N,N-dimethyl-formamide / dichloromethane / 15 - 25 °C
5.1: dichloromethane; water / 0 - 10 °C
6.1: borane-THF / tetrahydrofuran / 20 - 50 °C
6.2: 0.25 h / 0 - 5 °C
6.3: 2.5 h / 0 °C / Reflux
7.1: potassium carbonate; sodium iodide / 1-methyl-pyrrolidin-2-one / 20 - 60 °C / Inert atmosphere
7.2: 2 h / 20 °C
8.1: potassium carbonate / water / 0.08 h
8.2: Inert atmosphere
9.1: hydrogenchloride; hydrogen / palladium 10% on activated carbon / water / 6 h / 45 °C / 7500.75 Torr
View Scheme
(S)-3,4-dimethoxy-bicyclo[4.2.0]octa-1.3,5-triene-7-carboxylic acid (R)-(-)-1-(naphthyl)-ethylamine

(S)-3,4-dimethoxy-bicyclo[4.2.0]octa-1.3,5-triene-7-carboxylic acid (R)-(-)-1-(naphthyl)-ethylamine

ivabradine hydrochloride
148849-67-6

ivabradine hydrochloride

Conditions
ConditionsYield
Multi-step reaction with 7 steps
1.1: hydrogenchloride / dichloromethane; water / 0.33 h
2.1: oxalyl dichloride / N,N-dimethyl-formamide / dichloromethane / 15 - 25 °C
3.1: dichloromethane; water / 0 - 10 °C
4.1: borane-THF / tetrahydrofuran / 20 - 50 °C
4.2: 0.25 h / 0 - 5 °C
4.3: 2.5 h / 0 °C / Reflux
5.1: potassium carbonate; sodium iodide / 1-methyl-pyrrolidin-2-one / 20 - 60 °C / Inert atmosphere
5.2: 2 h / 20 °C
6.1: potassium carbonate / water / 0.08 h
6.2: Inert atmosphere
7.1: hydrogenchloride; hydrogen / palladium 10% on activated carbon / water / 6 h / 45 °C / 7500.75 Torr
View Scheme
3,4-dimethoxy-bicyclo[4.2.0]octa-1.3,5-triene-7-carboxylic acid cinchonidine

3,4-dimethoxy-bicyclo[4.2.0]octa-1.3,5-triene-7-carboxylic acid cinchonidine

ivabradine hydrochloride
148849-67-6

ivabradine hydrochloride

Conditions
ConditionsYield
Multi-step reaction with 7 steps
1.1: hydrogenchloride / ethyl acetate; water / 0.08 h / pH 3
2.1: oxalyl dichloride / N,N-dimethyl-formamide / dichloromethane / 15 - 25 °C
3.1: dichloromethane; water / 0 - 10 °C
4.1: borane-THF / tetrahydrofuran / 20 - 50 °C
4.2: 0.25 h / 0 - 5 °C
4.3: 2.5 h / 0 °C / Reflux
5.1: potassium carbonate; sodium iodide / 1-methyl-pyrrolidin-2-one / 20 - 60 °C / Inert atmosphere
5.2: 2 h / 20 °C
6.1: potassium carbonate / water / 0.08 h
6.2: Inert atmosphere
7.1: hydrogenchloride; hydrogen / palladium 10% on activated carbon / water / 6 h / 45 °C / 7500.75 Torr
View Scheme
Multi-step reaction with 10 steps
1.1: hydrogenchloride / ethyl acetate; water / 0.08 h / pH 3
2.1: potassium hydroxide / water / 4 h
2.2: 0.5 h / Cooling with ice-water bath
3.1: ethyl acetate / 1 h / 18 °C / Heating
4.1: hydrogenchloride / dichloromethane; water / 0.33 h
5.1: oxalyl dichloride / N,N-dimethyl-formamide / dichloromethane / 15 - 25 °C
6.1: dichloromethane; water / 0 - 10 °C
7.1: borane-THF / tetrahydrofuran / 20 - 50 °C
7.2: 0.25 h / 0 - 5 °C
7.3: 2.5 h / 0 °C / Reflux
8.1: potassium carbonate; sodium iodide / 1-methyl-pyrrolidin-2-one / 20 - 60 °C / Inert atmosphere
8.2: 2 h / 20 °C
9.1: potassium carbonate / water / 0.08 h
9.2: Inert atmosphere
10.1: hydrogenchloride; hydrogen / palladium 10% on activated carbon / water / 6 h / 45 °C / 7500.75 Torr
View Scheme
Multi-step reaction with 10 steps
1.1: hydrogenchloride / ethyl acetate; water / 0.08 h / pH 3
2.1: potassium hydroxide / water / 4 h
2.2: 0.5 h / Cooling with ice-water bath
3.1: ethyl acetate / 1 h / 18 °C / Heating
4.1: hydrogenchloride / dichloromethane; water / 0.33 h
5.1: oxalyl dichloride / N,N-dimethyl-formamide / dichloromethane / 15 - 25 °C
6.1: dichloromethane; water / 0 - 10 °C
7.1: borane-THF / tetrahydrofuran / 20 - 50 °C
7.2: 0.25 h / 0 - 5 °C
7.3: 2.5 h / 0 °C / Reflux
8.1: potassium carbonate; sodium iodide / 1-methyl-pyrrolidin-2-one / 20 - 60 °C / Inert atmosphere
8.2: 2 h / 20 °C
9.1: potassium carbonate / water / 0.08 h
9.2: Inert atmosphere
10.1: hydrogenchloride; hydrogen / palladium 10% on activated carbon / water / 6 h / 45 °C / 7500.75 Torr
View Scheme
Multi-step reaction with 10 steps
1.1: hydrogenchloride / ethyl acetate; water / 0.08 h / pH 3
2.1: potassium hydroxide / water / 4 h
2.2: 0.5 h / Cooling with ice-water bath
3.1: ethyl acetate / 1.25 h / 0 °C / Reflux
4.1: hydrogenchloride / dichloromethane; water / 0.08 h
5.1: oxalyl dichloride / N,N-dimethyl-formamide / dichloromethane / 15 - 25 °C
6.1: dichloromethane; water / 0 - 10 °C
7.1: borane-THF / tetrahydrofuran / 20 - 50 °C
7.2: 0.25 h / 0 - 5 °C
7.3: 2.5 h / 0 °C / Reflux
8.1: potassium carbonate; sodium iodide / 1-methyl-pyrrolidin-2-one / 20 - 60 °C / Inert atmosphere
8.2: 2 h / 20 °C
9.1: potassium carbonate / water / 0.08 h
9.2: Inert atmosphere
10.1: hydrogenchloride; hydrogen / palladium 10% on activated carbon / water / 6 h / 45 °C / 7500.75 Torr
View Scheme
Multi-step reaction with 10 steps
1.1: hydrogenchloride / ethyl acetate; water / 0.08 h / pH 3
2.1: potassium hydroxide / water / 4 h
2.2: 0.5 h / Cooling with ice-water bath
3.1: ethyl acetate / Heating
4.1: hydrogenchloride / dichloromethane; water / 0.33 h
5.1: oxalyl dichloride / N,N-dimethyl-formamide / dichloromethane / 15 - 25 °C
6.1: dichloromethane; water / 0 - 10 °C
7.1: borane-THF / tetrahydrofuran / 20 - 50 °C
7.2: 0.25 h / 0 - 5 °C
7.3: 2.5 h / 0 °C / Reflux
8.1: potassium carbonate; sodium iodide / 1-methyl-pyrrolidin-2-one / 20 - 60 °C / Inert atmosphere
8.2: 2 h / 20 °C
9.1: potassium carbonate / water / 0.08 h
9.2: Inert atmosphere
10.1: hydrogenchloride; hydrogen / palladium 10% on activated carbon / water / 6 h / 45 °C / 7500.75 Torr
View Scheme
3,4-dimethoxy-bicyclo[4.2.0]octa-1,3,5-triene-7-carboxylic acid (+)-cinchonine

3,4-dimethoxy-bicyclo[4.2.0]octa-1,3,5-triene-7-carboxylic acid (+)-cinchonine

ivabradine hydrochloride
148849-67-6

ivabradine hydrochloride

Conditions
ConditionsYield
Multi-step reaction with 10 steps
1.1: hydrogenchloride / water
2.1: potassium hydroxide / water / 4 h
2.2: 0.5 h / Cooling with ice-water bath
3.1: ethyl acetate / 1 h / 18 °C / Heating
4.1: hydrogenchloride / dichloromethane; water / 0.33 h
5.1: oxalyl dichloride / N,N-dimethyl-formamide / dichloromethane / 15 - 25 °C
6.1: dichloromethane; water / 0 - 10 °C
7.1: borane-THF / tetrahydrofuran / 20 - 50 °C
7.2: 0.25 h / 0 - 5 °C
7.3: 2.5 h / 0 °C / Reflux
8.1: potassium carbonate; sodium iodide / 1-methyl-pyrrolidin-2-one / 20 - 60 °C / Inert atmosphere
8.2: 2 h / 20 °C
9.1: potassium carbonate / water / 0.08 h
9.2: Inert atmosphere
10.1: hydrogenchloride; hydrogen / palladium 10% on activated carbon / water / 6 h / 45 °C / 7500.75 Torr
View Scheme
Multi-step reaction with 10 steps
1.1: hydrogenchloride / water
2.1: potassium hydroxide / water / 4 h
2.2: 0.5 h / Cooling with ice-water bath
3.1: acetone / 0.5 h / Reflux; Cooling
4.1: hydrogenchloride / ethyl acetate; water / 0.08 h / pH 3
5.1: oxalyl dichloride / N,N-dimethyl-formamide / dichloromethane / 15 - 25 °C
6.1: dichloromethane; water / 0 - 10 °C
7.1: borane-THF / tetrahydrofuran / 20 - 50 °C
7.2: 0.25 h / 0 - 5 °C
7.3: 2.5 h / 0 °C / Reflux
8.1: potassium carbonate; sodium iodide / 1-methyl-pyrrolidin-2-one / 20 - 60 °C / Inert atmosphere
8.2: 2 h / 20 °C
9.1: potassium carbonate / water / 0.08 h
9.2: Inert atmosphere
10.1: hydrogenchloride; hydrogen / palladium 10% on activated carbon / water / 6 h / 45 °C / 7500.75 Torr
View Scheme
Multi-step reaction with 10 steps
1.1: hydrogenchloride / water
2.1: potassium hydroxide / water / 4 h
2.2: 0.5 h / Cooling with ice-water bath
3.1: ethyl acetate / 1 h / 18 °C / Heating
4.1: hydrogenchloride / dichloromethane; water / 0.33 h
5.1: oxalyl dichloride / N,N-dimethyl-formamide / dichloromethane / 15 - 25 °C
6.1: dichloromethane; water / 0 - 10 °C
7.1: borane-THF / tetrahydrofuran / 20 - 50 °C
7.2: 0.25 h / 0 - 5 °C
7.3: 2.5 h / 0 °C / Reflux
8.1: potassium carbonate; sodium iodide / 1-methyl-pyrrolidin-2-one / 20 - 60 °C / Inert atmosphere
8.2: 2 h / 20 °C
9.1: potassium carbonate / water / 0.08 h
9.2: Inert atmosphere
10.1: hydrogenchloride; hydrogen / palladium 10% on activated carbon / water / 6 h / 45 °C / 7500.75 Torr
View Scheme
Multi-step reaction with 10 steps
1.1: hydrogenchloride / water
2.1: potassium hydroxide / water / 4 h
2.2: 0.5 h / Cooling with ice-water bath
3.1: ethyl acetate / Heating
4.1: hydrogenchloride / dichloromethane; water / 0.33 h
5.1: oxalyl dichloride / N,N-dimethyl-formamide / dichloromethane / 15 - 25 °C
6.1: dichloromethane; water / 0 - 10 °C
7.1: borane-THF / tetrahydrofuran / 20 - 50 °C
7.2: 0.25 h / 0 - 5 °C
7.3: 2.5 h / 0 °C / Reflux
8.1: potassium carbonate; sodium iodide / 1-methyl-pyrrolidin-2-one / 20 - 60 °C / Inert atmosphere
8.2: 2 h / 20 °C
9.1: potassium carbonate / water / 0.08 h
9.2: Inert atmosphere
10.1: hydrogenchloride; hydrogen / palladium 10% on activated carbon / water / 6 h / 45 °C / 7500.75 Torr
View Scheme
(7S)-3,4-dimethoxy-N-methylbicyclo[4.2.0]octa-1,3,5-triene-7-carboxamide
1220993-43-0

(7S)-3,4-dimethoxy-N-methylbicyclo[4.2.0]octa-1,3,5-triene-7-carboxamide

ivabradine hydrochloride
148849-67-6

ivabradine hydrochloride

Conditions
ConditionsYield
Multi-step reaction with 4 steps
1.1: borane-THF / tetrahydrofuran / 20 - 50 °C
1.2: 0.25 h / 0 - 5 °C
1.3: 2.5 h / 0 °C / Reflux
2.1: potassium carbonate; sodium iodide / 1-methyl-pyrrolidin-2-one / 20 - 60 °C / Inert atmosphere
2.2: 2 h / 20 °C
3.1: potassium carbonate / water / 0.08 h
3.2: Inert atmosphere
4.1: hydrogenchloride; hydrogen / palladium 10% on activated carbon / water / 6 h / 45 °C / 7500.75 Torr
View Scheme
Multi-step reaction with 2 steps
1.1: borane-THF / tetrahydrofuran / 20 °C
1.2: 4 h
2.1: hydrogen; palladium on activated charcoal / ethanol / 55 °C / 3750.38 Torr / Autoclave; Large scale
2.2: 85 °C / 22502.3 Torr / Autoclave; Large scale
View Scheme
(S)-3,4-dimethoxy-bicyclo[4.2.0]octa-1.3,5-triene-7-carboxylic acid chloride
1220993-45-2

(S)-3,4-dimethoxy-bicyclo[4.2.0]octa-1.3,5-triene-7-carboxylic acid chloride

ivabradine hydrochloride
148849-67-6

ivabradine hydrochloride

Conditions
ConditionsYield
Multi-step reaction with 5 steps
1.1: dichloromethane; water / 0 - 10 °C
2.1: borane-THF / tetrahydrofuran / 20 - 50 °C
2.2: 0.25 h / 0 - 5 °C
2.3: 2.5 h / 0 °C / Reflux
3.1: potassium carbonate; sodium iodide / 1-methyl-pyrrolidin-2-one / 20 - 60 °C / Inert atmosphere
3.2: 2 h / 20 °C
4.1: potassium carbonate / water / 0.08 h
4.2: Inert atmosphere
5.1: hydrogenchloride; hydrogen / palladium 10% on activated carbon / water / 6 h / 45 °C / 7500.75 Torr
View Scheme
dehydro-ivabradine oxalate
1346558-08-4

dehydro-ivabradine oxalate

ivabradine hydrochloride
148849-67-6

ivabradine hydrochloride

Conditions
ConditionsYield
Multi-step reaction with 2 steps
1.1: potassium carbonate / water / 0.08 h
1.2: Inert atmosphere
2.1: hydrogenchloride; hydrogen / palladium 10% on activated carbon / water / 6 h / 45 °C / 7500.75 Torr
View Scheme
3-(2-bromo-4,5-dimethoxyphenyl)propanenitrile
35249-62-8

3-(2-bromo-4,5-dimethoxyphenyl)propanenitrile

ivabradine hydrochloride
148849-67-6

ivabradine hydrochloride

Conditions
ConditionsYield
Multi-step reaction with 10 steps
1.1: n-butyllithium / hexane; tetrahydrofuran / -10 °C / Inert atmosphere
2.1: potassium hydroxide; water / 4 h / Reflux
2.2: 20 °C
3.1: ethyl acetate / 1.25 h / 0 °C / Reflux
4.1: hydrogenchloride / dichloromethane; water / 0.08 h
5.1: oxalyl dichloride / N,N-dimethyl-formamide / dichloromethane / 15 - 25 °C
6.1: dichloromethane; water / 0 - 10 °C
7.1: borane-THF / tetrahydrofuran / 20 - 50 °C
7.2: 0.25 h / 0 - 5 °C
7.3: 2.5 h / 0 °C / Reflux
8.1: potassium carbonate; sodium iodide / 1-methyl-pyrrolidin-2-one / 20 - 60 °C / Inert atmosphere
8.2: 2 h / 20 °C
9.1: potassium carbonate / water / 0.08 h
9.2: Inert atmosphere
10.1: hydrogenchloride; hydrogen / palladium 10% on activated carbon / water / 6 h / 45 °C / 7500.75 Torr
View Scheme
Multi-step reaction with 10 steps
1.1: n-butyllithium / hexane; tetrahydrofuran / -10 °C / Inert atmosphere
2.1: potassium hydroxide; water / 4 h / Reflux
2.2: 20 °C
3.1: acetone / 0.5 h / Reflux; Cooling
4.1: hydrogenchloride / ethyl acetate; water / 0.08 h / pH 3
5.1: oxalyl dichloride / N,N-dimethyl-formamide / dichloromethane / 15 - 25 °C
6.1: dichloromethane; water / 0 - 10 °C
7.1: borane-THF / tetrahydrofuran / 20 - 50 °C
7.2: 0.25 h / 0 - 5 °C
7.3: 2.5 h / 0 °C / Reflux
8.1: potassium carbonate; sodium iodide / 1-methyl-pyrrolidin-2-one / 20 - 60 °C / Inert atmosphere
8.2: 2 h / 20 °C
9.1: potassium carbonate / water / 0.08 h
9.2: Inert atmosphere
10.1: hydrogenchloride; hydrogen / palladium 10% on activated carbon / water / 6 h / 45 °C / 7500.75 Torr
View Scheme
Multi-step reaction with 10 steps
1.1: n-butyllithium / hexane; tetrahydrofuran / -10 °C / Inert atmosphere
2.1: potassium hydroxide; water / 4 h / Reflux
2.2: 20 °C
3.1: ethyl acetate / 1 h / 18 °C / Heating
4.1: hydrogenchloride / dichloromethane; water / 0.33 h
5.1: oxalyl dichloride / N,N-dimethyl-formamide / dichloromethane / 15 - 25 °C
6.1: dichloromethane; water / 0 - 10 °C
7.1: borane-THF / tetrahydrofuran / 20 - 50 °C
7.2: 0.25 h / 0 - 5 °C
7.3: 2.5 h / 0 °C / Reflux
8.1: potassium carbonate; sodium iodide / 1-methyl-pyrrolidin-2-one / 20 - 60 °C / Inert atmosphere
8.2: 2 h / 20 °C
9.1: potassium carbonate / water / 0.08 h
9.2: Inert atmosphere
10.1: hydrogenchloride; hydrogen / palladium 10% on activated carbon / water / 6 h / 45 °C / 7500.75 Torr
View Scheme
Multi-step reaction with 10 steps
1.1: n-butyllithium / hexane; tetrahydrofuran / -10 °C / Inert atmosphere
2.1: potassium hydroxide; water / 4 h / Reflux
2.2: 20 °C
3.1: ethyl acetate / 1 h / 18 °C / Heating
4.1: hydrogenchloride / dichloromethane; water / 0.33 h
5.1: oxalyl dichloride / N,N-dimethyl-formamide / dichloromethane / 15 - 25 °C
6.1: dichloromethane; water / 0 - 10 °C
7.1: borane-THF / tetrahydrofuran / 20 - 50 °C
7.2: 0.25 h / 0 - 5 °C
7.3: 2.5 h / 0 °C / Reflux
8.1: potassium carbonate; sodium iodide / 1-methyl-pyrrolidin-2-one / 20 - 60 °C / Inert atmosphere
8.2: 2 h / 20 °C
9.1: potassium carbonate / water / 0.08 h
9.2: Inert atmosphere
10.1: hydrogenchloride; hydrogen / palladium 10% on activated carbon / water / 6 h / 45 °C / 7500.75 Torr
View Scheme
Multi-step reaction with 10 steps
1.1: n-butyllithium / hexane; tetrahydrofuran / -10 °C / Inert atmosphere
2.1: potassium hydroxide; water / 4 h / Reflux
2.2: 20 °C
3.1: ethyl acetate / Heating
4.1: hydrogenchloride / dichloromethane; water / 0.33 h
5.1: oxalyl dichloride / N,N-dimethyl-formamide / dichloromethane / 15 - 25 °C
6.1: dichloromethane; water / 0 - 10 °C
7.1: borane-THF / tetrahydrofuran / 20 - 50 °C
7.2: 0.25 h / 0 - 5 °C
7.3: 2.5 h / 0 °C / Reflux
8.1: potassium carbonate; sodium iodide / 1-methyl-pyrrolidin-2-one / 20 - 60 °C / Inert atmosphere
8.2: 2 h / 20 °C
9.1: potassium carbonate / water / 0.08 h
9.2: Inert atmosphere
10.1: hydrogenchloride; hydrogen / palladium 10% on activated carbon / water / 6 h / 45 °C / 7500.75 Torr
View Scheme
7,8-dimethoxy-2-oxo-2,3,4,5-tetrahydro-1H-3-benzazepine
20925-64-8

7,8-dimethoxy-2-oxo-2,3,4,5-tetrahydro-1H-3-benzazepine

(S)-3-chloro-N-((3,4-dimethoxybicyclo[4.2,0]octa-1(6),2,4-trien-7-yl)methyl)-N-methylpropan-1-amine
1031767-71-1

(S)-3-chloro-N-((3,4-dimethoxybicyclo[4.2,0]octa-1(6),2,4-trien-7-yl)methyl)-N-methylpropan-1-amine

ivabradine hydrochloride
148849-67-6

ivabradine hydrochloride

Conditions
ConditionsYield
Stage #1: 7,8-dimethoxy-2-oxo-2,3,4,5-tetrahydro-1H-3-benzazepine With potassium tert-butylate In dimethyl sulfoxide for 1.08333h; Inert atmosphere;
Stage #2: (S)-3-chloro-N-((3,4-dimethoxybicyclo[4.2,0]octa-1(6),2,4-trien-7-yl)methyl)-N-methylpropan-1-amine In dimethyl sulfoxide at 25 - 30℃;
Stage #3: With hydrogenchloride In isopropyl alcohol; acetonitrile at 15 - 20℃; for 12h; pH=1 - 2; Inert atmosphere;
1-[(7S)-3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl]-N-methylmethanamine camphorsulphonic acid salt

1-[(7S)-3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl]-N-methylmethanamine camphorsulphonic acid salt

ivabradine hydrochloride
148849-67-6

ivabradine hydrochloride

Conditions
ConditionsYield
Multi-step reaction with 2 steps
1.1: sodium hydroxide
1.2: 5 h / 20 °C / Inert atmosphere
2.1: potassium tert-butylate / dimethyl sulfoxide / 1.08 h / Inert atmosphere
2.2: 25 - 30 °C
2.3: 12 h / 15 - 20 °C / pH 1 - 2 / Inert atmosphere
View Scheme
[{(7S)-3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl}methyl](methyl)amine
866783-12-2

[{(7S)-3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl}methyl](methyl)amine

ivabradine hydrochloride
148849-67-6

ivabradine hydrochloride

Conditions
ConditionsYield
Multi-step reaction with 3 steps
1.1: potassium carbonate / 20 °C
2.1: potassium tert-butylate / dimethyl sulfoxide / 1 h / 20 °C
2.2: 20 °C
3.1: hydrogenchloride / diethyl ether; acetonitrile
View Scheme
Multi-step reaction with 4 steps
1.1: potassium carbonate / 20 °C
2.1: potassium tert-butylate / dimethyl sulfoxide / 0.5 h / 20 °C
2.2: 20 °C
3.1: hydrogen; acetic acid / 20% palladium hydroxide-activated charcoal / ethanol / 5 h / 20 °C / 3750.38 Torr
4.1: hydrogenchloride / diethyl ether; acetonitrile
View Scheme
Multi-step reaction with 3 steps
1: potassium carbonate; potassium iodide / 48 h / 85 - 90 °C
2: hydrogenchloride / acetonitrile / 20 - 25 °C
3: 5%-palladium/activated carbon; hydrogen / methanol / 18 h / 30 - 35 °C / 3000.3 - 3750.38 Torr / Autoclave
View Scheme
Multi-step reaction with 3 steps
1.1: acetic acid / ethanol / 0.5 h / 20 °C
1.2: 1 h / 15 - 20 °C
2.1: triethylamine / acetonitrile / 12 h / 20 °C
3.1: hydrogenchloride; pyrographite / acetonitrile / 0.17 h / 70 °C / pH 2 - 3
View Scheme
(S)-3-chloro-N-((3,4-dimethoxybicyclo[4.2,0]octa-1(6),2,4-trien-7-yl)methyl)-N-methylpropan-1-amine
1031767-71-1

(S)-3-chloro-N-((3,4-dimethoxybicyclo[4.2,0]octa-1(6),2,4-trien-7-yl)methyl)-N-methylpropan-1-amine

ivabradine hydrochloride
148849-67-6

ivabradine hydrochloride

Conditions
ConditionsYield
Multi-step reaction with 2 steps
1.1: potassium tert-butylate / dimethyl sulfoxide / 1 h / 20 °C
1.2: 20 °C
2.1: hydrogenchloride / diethyl ether; acetonitrile
View Scheme
Multi-step reaction with 3 steps
1.1: potassium tert-butylate / dimethyl sulfoxide / 0.5 h / 20 °C
1.2: 20 °C
2.1: hydrogen; acetic acid / 20% palladium hydroxide-activated charcoal / ethanol / 5 h / 20 °C / 3750.38 Torr
3.1: hydrogenchloride / diethyl ether; acetonitrile
View Scheme
[{(7S)-3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl}methyl](methyl)amine
866783-12-2

[{(7S)-3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl}methyl](methyl)amine

3-(3-chloropropyl)-7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one
85175-65-1

3-(3-chloropropyl)-7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one

ivabradine hydrochloride
148849-67-6

ivabradine hydrochloride

Conditions
ConditionsYield
Stage #1: [{(7S)-3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl}methyl](methyl)amine; 7,8-dimethoxy-3-(3-chloropropyl)-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one With potassium carbonate; sodium iodide In acetone at 20 - 65℃;
Stage #2: With triethylamine; acetyl chloride In toluene
Stage #3: With hydrogenchloride In water; toluene pH=2 - 3; Product distribution / selectivity;
3-(3-chloropropyl)-1,3-dihydro-7,8-dimethoxy-2H-3-benzazepine-2-one
85175-59-3

3-(3-chloropropyl)-1,3-dihydro-7,8-dimethoxy-2H-3-benzazepine-2-one

ivabradine hydrochloride
148849-67-6

ivabradine hydrochloride

Conditions
ConditionsYield
Multi-step reaction with 3 steps
1: potassium carbonate; potassium iodide / 48 h / 85 - 90 °C
2: hydrogenchloride / acetonitrile / 20 - 25 °C
3: 5%-palladium/activated carbon; hydrogen / methanol / 18 h / 30 - 35 °C / 3000.3 - 3750.38 Torr / Autoclave
View Scheme
Multi-step reaction with 2 steps
1.1: potassium carbonate / water / 30 °C
1.2: 55 - 60 °C
2.1: hydrogen; palladium 10% on activated carbon / methanol / 25 - 30 °C / 5250.53 - 6000.6 Torr
View Scheme
Multi-step reaction with 3 steps
1.1: sodium iodide / butanone / 8 h / Reflux
2.1: potassium carbonate / water / 30 °C
2.2: 24.5 h / 30 - 60 °C
3.1: ammonium formate; palladium 10% on activated carbon; hydrogen / methanol / 25 - 30 °C
View Scheme
(R)-(3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl)nitrile
1214788-46-1

(R)-(3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl)nitrile

ivabradine hydrochloride
148849-67-6

ivabradine hydrochloride

Conditions
ConditionsYield
Multi-step reaction with 5 steps
1.1: 1,8-diazabicyclo[5.4.0]undec-7-ene / isopropyl alcohol / 2 h / 65 °C
2.1: nitrilase of Rhodococcus erythropolis NCIMB11215 / aq. phosphate buffer; dimethyl sulfoxide / 96 h / 30 °C / pH 7.3 / Enzymatic reaction
3.1: chloroformic acid ethyl ester; triethylamine / tetrahydrofuran / 20 °C
3.2: 20 °C
4.1: borane-THF / tetrahydrofuran / 20 °C
4.2: 4 h
5.1: hydrogen; palladium on activated charcoal / ethanol / 55 °C / 3750.38 Torr / Autoclave; Large scale
5.2: 85 °C / 22502.3 Torr / Autoclave; Large scale
View Scheme
Multi-step reaction with 5 steps
1.1: 1,8-diazabicyclo[5.4.0]undec-7-ene / isopropyl alcohol / 2 h / 65 °C
2.1: nitrilase of Rhodococcus rhodochrous NCIMB11216 / aq. phosphate buffer; dimethyl sulfoxide / 96 h / 30 °C / pH 7.3 / Enzymatic reaction
3.1: chloroformic acid ethyl ester; triethylamine / tetrahydrofuran / 20 °C
3.2: 20 °C
4.1: borane-THF / tetrahydrofuran / 20 °C
4.2: 4 h
5.1: hydrogen; palladium on activated charcoal / ethanol / 55 °C / 3750.38 Torr / Autoclave; Large scale
5.2: 85 °C / 22502.3 Torr / Autoclave; Large scale
View Scheme
Multi-step reaction with 5 steps
1.1: 1,8-diazabicyclo[5.4.0]undec-7-ene / isopropyl alcohol / 2 h / 65 °C
2.1: over-expressed nitrilase of Rhodococcus rhodochrous NCIMB 11216 / aq. phosphate buffer; dimethyl sulfoxide / 6 h / 30 °C / pH 7 / Enzymatic reaction
3.1: chloroformic acid ethyl ester; triethylamine / tetrahydrofuran / 20 °C
3.2: 20 °C
4.1: borane-THF / tetrahydrofuran / 20 °C
4.2: 4 h
5.1: hydrogen; palladium on activated charcoal / ethanol / 55 °C / 3750.38 Torr / Autoclave; Large scale
5.2: 85 °C / 22502.3 Torr / Autoclave; Large scale
View Scheme
ethyl ((3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl)methyl)carbamate
148870-55-7

ethyl ((3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl)methyl)carbamate

ivabradine hydrochloride
148849-67-6

ivabradine hydrochloride

Conditions
ConditionsYield
Multi-step reaction with 2 steps
1.1: lithium aluminium tetrahydride / tetrahydrofuran / 1 h / Reflux
1.2: 1 h / 15 - 20 °C
2.1: hydrogen; palladium on activated charcoal / water; ethanol / 85 °C / 22502.3 Torr / Autoclave
View Scheme
[{(7S)-3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl}methyl](methyl)amine
866783-12-2

[{(7S)-3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl}methyl](methyl)amine

(1S)-10-camphorsulfonic acid
3144-16-9

(1S)-10-camphorsulfonic acid

ivabradine
155974-00-8

ivabradine

A

[{(7S)-3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl}methyl](methyl)amine d-camphorsulfonate
1031767-75-5

[{(7S)-3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl}methyl](methyl)amine d-camphorsulfonate

B

ivabradine hydrochloride
148849-67-6

ivabradine hydrochloride

Conditions
ConditionsYield
Stage #1: [{(7S)-3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl}methyl](methyl)amine; (1S)-10-camphorsulfonic acid; ivabradine In toluene; acetonitrile at 20℃; for 1h;
Stage #2: With hydrogenchloride In water; toluene; acetonitrile at 0 - 5℃; for 2h;
(3,4-Dimethoxyphenyl)acetic acid
93-40-3

(3,4-Dimethoxyphenyl)acetic acid

ivabradine hydrochloride
148849-67-6

ivabradine hydrochloride

Conditions
ConditionsYield
Multi-step reaction with 5 steps
1.1: toluene / 30 h / Reflux
2.1: hydrogenchloride; sulfuric acid / water / 4 h / 25 - 30 °C / Reflux
3.1: potassium hydroxide / N,N-dimethyl-formamide / 0.25 h / 0 - 5 °C
3.2: 3 h / 0 - 5 °C
4.1: potassium carbonate / water / 30 °C
4.2: 55 - 60 °C
5.1: hydrogen; palladium 10% on activated carbon / methanol / 25 - 30 °C / 5250.53 - 6000.6 Torr
View Scheme
embonic acid disodium salt
6640-22-8, 7681-47-2, 15537-67-4

embonic acid disodium salt

ivabradine hydrochloride
148849-67-6

ivabradine hydrochloride

3-{3-[{ [(7S)-3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl]methyl}-(methyl)amino]propyl}-7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one hemi 4,4’-methanediylbis(3-hydroxynaphthalene-2-carboxylic) acid

3-{3-[{ [(7S)-3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl]methyl}-(methyl)amino]propyl}-7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one hemi 4,4’-methanediylbis(3-hydroxynaphthalene-2-carboxylic) acid

Conditions
ConditionsYield
In water for 0.5h;66.5%
ivabradine hydrochloride
148849-67-6

ivabradine hydrochloride

ivabradine
155974-00-8

ivabradine

Conditions
ConditionsYield
With sodium hydroxide In water Product distribution / selectivity;
ivabradine hydrochloride
148849-67-6

ivabradine hydrochloride

{2-[2-({3-[{[(7S)-3,4-dimethoxybicyclo[4.2.0]octa-4,3,5-trien-7-yl]methyl}(methyl)-amino]propyl}amino)ethyl]-4,5-dimethoxyphenyl}acetic acid
1462470-54-7

{2-[2-({3-[{[(7S)-3,4-dimethoxybicyclo[4.2.0]octa-4,3,5-trien-7-yl]methyl}(methyl)-amino]propyl}amino)ethyl]-4,5-dimethoxyphenyl}acetic acid

Conditions
ConditionsYield
With water; sodium hydroxide In acetonitrile at 80℃; for 1h;

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