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Dayang Chem (Hangzhou) Co.,Ltd.

Dayangchem's R&D center can offer custom synthesis according to the contract research and development services for the fine chemicals, pharmaceutical, biotechnique and some of the other chemicals. DayangChem can provide different quantities

Roflumilast Manufacturer/High quality/Best price/In stock

Cas:162401-32-3

Min.Order:1 Kilogram

FOB Price: $3.0

Type:Lab/Research institutions

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Wuhan Fortuna Chemical Co.,Ltd

Unique advantages for Roflumilast Cas 162401-32-3 Guaranteed purity High quality & competitive price Quality control Fast feedback Prompt shipment Appearance:White or off-white powder Storage:Refrigerator Package:100g,1kg/foil bag;25k

Manufacturer supply Roflumilast Cas 162401-32-3 with high quality and best price

Cas:162401-32-3

Min.Order:100 Gram

FOB Price: $3.0 / 5.0

Type:Trading Company

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Hangzhou Think Chemical Co. Ltd

Roflumilast CAS No.:162401-32-3 Name: Roflumilast Synonyms: 3-(Cyclopropylmethoxy)-N-(3,5-dichloropyridin-4-yl)-4-(difluoromethoxy)benzamide Molecular Structure Molecular

High purity Roflumilast CAS No.:162401-32-3

Cas:162401-32-3

Min.Order:1 Kilogram

FOB Price: $2.0

Type:Other

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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 Roflumilast

Cas:162401-32-3

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

High Quality 99% Roflumilast 162401-32-3 GMP manufacturer

Cas:162401-32-3

Min.Order:1 Gram

FOB Price: $0.1

Type:Manufacturers

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Enke Pharma-tech Co.,Ltd. (Cangzhou, China )

Cangzhou Enke Pharma Tech Co.,ltd. is located in Cangzhou City, Hebei province ,where is a famous petroleum chemical industry city in China. Enke Pharma a high-tech enterprise ,and we are dedicated to developing and manufacturing new api, intermedi

Roflumilast

Cas:162401-32-3

Min.Order:1 Kilogram

FOB Price: $5.0 / 6.0

Type:Manufacturers

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Shanghai Seasonsgreen Chemical Co.,Ltd

Shanghai Seasonsgreen Chemical is a high-tech research and development, production, sale and custom synthesis set in one high-tech chemical products enterprises. Our sales and marketing division is located in Shanghai, serving international pharmaceu

lower price High quality Roflumilast

Cas:162401-32-3

Min.Order:1 Kilogram

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

Factory Roflumilast CAS 162401-32-3 stock 1.3kg CAS NO.162401-32-3

Cas:162401-32-3

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

Roflumilast

Cas:162401-32-3

Min.Order:5 Kiloliter

FOB Price: $1.2 / 5.0

Type:Manufacturers

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Hubei DiBo chemical co., LTD

Name:Cephalexin CAS:162401-32-3 Grade:For chemical industry, scientific research and export Product Quality 12 years of chemical raw materials Mature operation of the industry System stability Data storage Security without vulnerability P

Manufacturer supply Roflumilast with good price,162401-32-3

Cas:162401-32-3

Min.Order:25 Kilogram

FOB Price: $1.0 / 2.0

Type:Other

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Henan Tianfu Chemical Co., Ltd.

Roflumilast Basic information Physical and chemical properties Phosphodiesterase 4 (PDE4) inhibitors Indications PharmacokineticsDosage Patents Product Name: Roflumilast Synonyms:

Roflumilast 162401-32-3

Cas:162401-32-3

Min.Order:1 Kilogram

Negotiable

Type:Lab/Research institutions

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Hebei Nengqian Chemical Import and Export Co., LTD

Our advantages: 1, High quality with competitive price: 1) Standard:BP/USP/EP/Enterprise standard 2) All Purity≥99% 3) We are manufacturer and can provide high quality products with factory price. 2, Fast and safe delivery 1) Parcel can be sent

Roflumilast

Cas:162401-32-3

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

Pharmaceutical Grade CAS 162401-32-3 with competitive price

Cas:162401-32-3

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

Roflumilast CAS 162401-32-3

Cas:162401-32-3

Min.Order:10 Kilogram

Negotiable

Type:Trading Company

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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

Roflumilast/ LIDE PHARMA- Factory supply / Best price

Cas:162401-32-3

Min.Order:1 Gram

Negotiable

Type:Lab/Research institutions

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Henan Sinotech Import&Export Corporation

Product name Roflumilast Synonyms 3-CyclopropylMethoxy-N-(3,5-dichloro-pyridin-4-yl)-4-isopropoxy-benzaMide;APTA 2217;3-Cyclopropylmethoxy-4-difluoromethoxy-N-[3,5-dichloropyrid-4-yl]-benzamide;1

Roflumilast

Cas:162401-32-3

Min.Order:1 Metric Ton

FOB Price: $1.0

Type:Other

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Hubei Langyou International Trading Co., Ltd

1. Guaranteed purity; 2. Large quantity in stock; 3. Largest manufacturer; 4. Best service after shipment with email; 5. High quality & competitive price; Appearance:White Crystalline Powder Storage:Store in sealed conta

high quality 162401-32-3 Roflumilast with best price

Cas:162401-32-3

Min.Order:10 Gram

Negotiable

Type:Other

inquiry

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

Benzamide,3-(cyclopropylmethoxy)-N-(3,5-dichloro-4-pyridinyl)-4-(difluoromethoxy)- 162401-32-3

Cas:162401-32-3

Min.Order:1 Kilogram

Negotiable

Type:Lab/Research institutions

inquiry

Xi'an Faithful Biotech Co., Ltd.

We are the manufacturers and suppliers of API in China, and warehouse in Germany and USA of California, which can quickly and safely deliver to your address 1.High quality and competitive price. 2.Free sample for your evaluation. 3.Promptly delivery

Shanghai Minstar Chemical Co., Ltd

Product Name: Roflumilast Synonyms: ROFLUMILAST;3-(Cyclopropylmethoxy)-N-(3,5-dichloro-4-pyridinyl)-4-(difluoromethoxy)benzamide;B 9302-107;BY 217;BYK 20869;Daxas;Roflumilast / 3-(cyclopropylmethoxy)-N-(3,5-dichloropyridin-4-yl)-4-(difluorometh

Roflumilast

Cas:162401-32-3

Min.Order:1 Gram

Negotiable

Type:Lab/Research institutions

inquiry

Baoji Guokang Healthchem co.,ltd

Our company has been in existence for 10 years since its establishment. We have our own unique team. The company integrates independent research and development, production and sales. We have established famous brands at home and abroad. At prese

Asthma ,Roflumilast CAS:162401-32-3

Cas:162401-32-3

Min.Order:1 Kilogram

FOB Price: $64.0 / 69.0

Type:Trading Company

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Qingdao Beluga Import and Export Co., LTD

Roflumilast CAS:162401-32-3 Qingdao Belugas Import and Export Co., Ltd. is a scientific and technological company integrating research and development, production and trade of chemical intermediates, specializing in high quality organic intermediate

Roflumilast CAS:162401-32-3

Cas:162401-32-3

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

Roflumilast Powder USP Standard

Cas:162401-32-3

Min.Order:1 Kilogram

Negotiable

Type:Lab/Research institutions

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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

roflumilast manufacturer with low price

Cas:162401-32-3

Min.Order:1 Gram

Negotiable

Type:Trading Company

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Leader Biochemical Group

About Product Details

China Biggest Factory Manufacturer Supply Roflumilast CAS 162401-32-3

Cas:162401-32-3

Min.Order:500 Kilogram

FOB Price: $1.0 / 2.0

Type:Lab/Research institutions

inquiry

Hangzhou Sartort Biopharma Co., Ltd

Appearance:White crystalline powder Storage:R.T Package:50G/Bottle, 100G/Bottle, 1KG/Bottle or at customers requirement. Application:COPD treatment Transportation:Express/Sea/Air Port:Any port in China

API Roflumilast cas 162401-32-3

Cas:162401-32-3

Min.Order:100 Gram

Negotiable

Type:Lab/Research institutions

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Lonwin Chemical Group Limited

Roflumilast CAS: 162401-32-3 Specification Item Standard Structural data confirmation 1. H-NMR: The data of structure are identical with reference standard 2. HPLC-MS: Ensure the

Factory supply Roflumilast

Cas:162401-32-3

Min.Order:1 Kilogram

Negotiable

Type:Other

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

Benzamide,3-(cyclopropylmethoxy)-N-(3,5-dichloro-4-pyridinyl)-4-(difluoromethoxy)-

Cas:162401-32-3

Min.Order:0

Negotiable

Type:Lab/Research institutions

inquiry

ShangHai Soyoung Biotechnology Inc

Shanghai SOYOUNG onsite assessment conducted by Bureau Veritas commissioned at June 2018. Assessed Supplier of Shanghai SOYOUNG is a faithful and professional supplier of health raw materials in pharmacy, food, cosmetic and other fields for many ye

Roflumilast 162401-32-3

Cas:162401-32-3

Min.Order:1 Kilogram

FOB Price: $4900.0

Type:Lab/Research institutions

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Triumph International Development Limilted

Product name: sodium metabisulfite / sodium metabisulphite Molecular weight: 190.10 Specification: 25Kg woven bag Quality guarantee period: 6 months Appearance:White or off white crystalline powder Storage:Store in a well-closed pl

Roflumilast

Cas:162401-32-3

Min.Order:10 Gram

FOB Price: $10.0

Type:Lab/Research institutions

inquiry

Synthetic route

3-(cyclopropylmethoxy)-4-(difluoromethoxy)-benzoic acid
162401-62-9

3-(cyclopropylmethoxy)-4-(difluoromethoxy)-benzoic acid

3,5-dichloro-4-aminopyridine
22889-78-7

3,5-dichloro-4-aminopyridine

roflumilast
162401-32-3

roflumilast

Conditions
ConditionsYield
Stage #1: 3-(cyclopropylmethoxy)-4-(difluoromethoxy)-benzoic acid With pyridine; 2,4,6-trinitrochlorobenzene In 1,4-dioxane at 20 - 35℃; for 3h; Industrial scale;
Stage #2: 3,5-dichloro-4-aminopyridine In 1,4-dioxane for 2h; Reagent/catalyst; Solvent; Temperature; Industrial scale;
95%
Stage #1: 3-(cyclopropylmethoxy)-4-(difluoromethoxy)-benzoic acid With 4-methyl-morpholine; 2-chloro-4,6-dimethoxy-1 ,3,5-triazine In dichloromethane at 0 - 20℃; for 3h;
Stage #2: 3,5-dichloro-4-aminopyridine In dichloromethane for 2h; Concentration;
91%
Stage #1: 3-(cyclopropylmethoxy)-4-(difluoromethoxy)-benzoic acid With pivaloyl chloride; sodium carbonate In tetrahydrofuran at 25℃; for 2h;
Stage #2: 3,5-dichloro-4-aminopyridine In tetrahydrofuran at 50℃; for 4h; Temperature; Solvent; Reagent/catalyst;
64%
Stage #1: 3-(cyclopropylmethoxy)-4-(difluoromethoxy)-benzoic acid With thionyl chloride In toluene Heating / reflux;
Stage #2: 3,5-dichloro-4-aminopyridine With sodium hydride In tetrahydrofuran for 1h; Cooling;
58.6%
3,5-dichloro-4-aminopyridine
22889-78-7

3,5-dichloro-4-aminopyridine

3-(difluoromethoxy)-4-(cyclopropylmethoxy)-benzoic acid
162401-69-6

3-(difluoromethoxy)-4-(cyclopropylmethoxy)-benzoic acid

roflumilast
162401-32-3

roflumilast

Conditions
ConditionsYield
Stage #1: 3-(difluoromethoxy)-4-(cyclopropylmethoxy)-benzoic acid With thionyl chloride In toluene for 2h; Reflux;
Stage #2: 3,5-dichloro-4-aminopyridine With sodium hydride In tetrahydrofuran at 15 - 20℃;
95%
3-(cyclopropylmethoxy)-4-(difluoromethoxy)-benzoic acid
162401-62-9

3-(cyclopropylmethoxy)-4-(difluoromethoxy)-benzoic acid

roflumilast
162401-32-3

roflumilast

Conditions
ConditionsYield
Large scale;93%
Multi-step reaction with 2 steps
1.1: dimethyl sulfoxide / 3 h / 20 °C
2.1: cesium fluoride / dimethyl sulfoxide / 3 h / 90 °C
2.2: 6.5 h / 90 - 95 °C
View Scheme
3,5-dichloro-N-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)benzylidene)pyridin-4-amine
1454574-39-0

3,5-dichloro-N-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)benzylidene)pyridin-4-amine

roflumilast
162401-32-3

roflumilast

Conditions
ConditionsYield
With sodium chlorite; 2-methyl-but-2-ene; acetic acid In water; acetonitrile at 20 - 30℃; for 3h; Cooling with ice;92.4%
With sodium chlorite; 2-methyl-but-2-ene; acetic acid In water; acetonitrile at 20 - 30℃; for 2h; Reagent/catalyst; Cooling with ice;82%
With sodium chlorite; sodium dihydrogenphosphate; 2-methyl-but-2-ene In tetrahydrofuran; water57%
3,5-dichloro-4-aminopyridine
22889-78-7

3,5-dichloro-4-aminopyridine

(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)(1H-imidazol-1-yl)methanone
1590361-85-5

(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)(1H-imidazol-1-yl)methanone

roflumilast
162401-32-3

roflumilast

Conditions
ConditionsYield
Stage #1: 3,5-dichloro-4-aminopyridine With cesium fluoride In dimethyl sulfoxide at 90℃; for 3h;
Stage #2: (3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)(1H-imidazol-1-yl)methanone In dimethyl sulfoxide at 90 - 95℃; for 6.5h; Reagent/catalyst;
88%
BYK20839
1391052-76-8

BYK20839

cyclopropylcarbinyl bromide
7051-34-5

cyclopropylcarbinyl bromide

roflumilast
162401-32-3

roflumilast

Conditions
ConditionsYield
With potassium carbonate In N,N-dimethyl-formamide at 80℃; for 2h; Temperature;82.3%
3,5-dichloro-4-aminopyridine
22889-78-7

3,5-dichloro-4-aminopyridine

(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)(1H-1,2,4-triazol-1-yl)methanone
1601300-21-3

(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)(1H-1,2,4-triazol-1-yl)methanone

roflumilast
162401-32-3

roflumilast

Conditions
ConditionsYield
Stage #1: 3,5-dichloro-4-aminopyridine With cesium fluoride In dimethyl sulfoxide at 90℃; for 3h;
Stage #2: (3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)(1H-1,2,4-triazol-1-yl)methanone In dimethyl sulfoxide at 90 - 95℃; for 3h;
79%
Potassium salt of 4-amino-3, 5-dichloropyridine

Potassium salt of 4-amino-3, 5-dichloropyridine

3-(cyclopropylmethoxy)-4-(difluoromethoxy)benzoyl chloride
672883-68-0

3-(cyclopropylmethoxy)-4-(difluoromethoxy)benzoyl chloride

roflumilast
162401-32-3

roflumilast

Conditions
ConditionsYield
In DMF (N,N-dimethyl-formamide) at 15 - 40℃;
In 1-methyl-pyrrolidin-2-one at 15 - 40℃;
In DMF (N,N-dimethyl-formamide) at 15 - 40℃;
In DMF (N,N-dimethyl-formamide) at 15 - 40℃;
In tetrahydrofuran at 0 - 10℃; for 2.5h;
3,5-dichloro-4-aminopyridine
22889-78-7

3,5-dichloro-4-aminopyridine

3-(cyclopropylmethoxy)-4-(difluoromethoxy)benzoyl chloride
672883-68-0

3-(cyclopropylmethoxy)-4-(difluoromethoxy)benzoyl chloride

roflumilast
162401-32-3

roflumilast

Conditions
ConditionsYield
With sodium hydride In tetrahydrofuran at 0℃; for 0.5h;
Stage #1: 3,5-dichloro-4-aminopyridine With sodium hydroxide In toluene for 2h;
Stage #2: 3-(cyclopropylmethoxy)-4-(difluoromethoxy)benzoyl chloride In toluene for 6h; Concentration; Temperature; Time; Reflux;
89.2 %Chromat.
Stage #1: 3,5-dichloro-4-aminopyridine With sodium hydride In tetrahydrofuran for 0.5h;
Stage #2: 3-(cyclopropylmethoxy)-4-(difluoromethoxy)benzoyl chloride In tetrahydrofuran at 20 - 30℃; for 1h;
3-hydroxy-4-iodobenzoic acid
58123-77-6

3-hydroxy-4-iodobenzoic acid

roflumilast
162401-32-3

roflumilast

Conditions
ConditionsYield
Multi-step reaction with 7 steps
1: thionyl chloride / 3 h / 50 °C
2: potassium carbonate / N,N-dimethyl-formamide / 2 h / 80 °C / Large scale
3: potassium hydroxide; copper(l) iodide; 8-quinolinol / dimethyl sulfoxide / 30 h / 100 °C / Inert atmosphere; Large scale
4: thionyl chloride / 3 h / 50 °C
5: potassium carbonate / N,N-dimethyl-formamide / 1.25 h / 95 °C
6: sodium hydroxide / methanol / 3 h / 50 °C
7: Large scale
View Scheme
Multi-step reaction with 7 steps
1: thionyl chloride / 3 h / 50 °C
2: potassium carbonate / N,N-dimethyl-formamide / 2 h / 80 °C / Large scale
3: potassium hydroxide; copper(l) iodide; 8-quinolinol / dimethyl sulfoxide / 30 h / 100 °C / Inert atmosphere; Large scale
4: thionyl chloride / 3 h / 50 °C
5: N,N-dimethyl-formamide / Heating
6: sodium hydroxide / methanol / 3 h / 50 °C
7: Large scale
View Scheme
methyl 3-hydroxy-4-iodobenzoate
157942-12-6

methyl 3-hydroxy-4-iodobenzoate

roflumilast
162401-32-3

roflumilast

Conditions
ConditionsYield
Multi-step reaction with 6 steps
1: potassium carbonate / N,N-dimethyl-formamide / 2 h / 80 °C / Large scale
2: potassium hydroxide; copper(l) iodide; 8-quinolinol / dimethyl sulfoxide / 30 h / 100 °C / Inert atmosphere; Large scale
3: thionyl chloride / 3 h / 50 °C
4: potassium carbonate / N,N-dimethyl-formamide / 1.25 h / 95 °C
5: sodium hydroxide / methanol / 3 h / 50 °C
6: Large scale
View Scheme
Multi-step reaction with 6 steps
1: potassium carbonate / N,N-dimethyl-formamide / 2 h / 80 °C / Large scale
2: potassium hydroxide; copper(l) iodide; 8-quinolinol / dimethyl sulfoxide / 30 h / 100 °C / Inert atmosphere; Large scale
3: thionyl chloride / 3 h / 50 °C
4: N,N-dimethyl-formamide / Heating
5: sodium hydroxide / methanol / 3 h / 50 °C
6: Large scale
View Scheme
methyl 3-(cyclopropylmethoxy)-4-iodobenzoate
1392191-29-5

methyl 3-(cyclopropylmethoxy)-4-iodobenzoate

roflumilast
162401-32-3

roflumilast

Conditions
ConditionsYield
Multi-step reaction with 5 steps
1: potassium hydroxide; copper(l) iodide; 8-quinolinol / dimethyl sulfoxide / 30 h / 100 °C / Inert atmosphere; Large scale
2: thionyl chloride / 3 h / 50 °C
3: N,N-dimethyl-formamide / Heating
4: sodium hydroxide / methanol / 3 h / 50 °C
5: Large scale
View Scheme
Multi-step reaction with 5 steps
1: potassium hydroxide; copper(l) iodide; 8-quinolinol / dimethyl sulfoxide / 30 h / 100 °C / Inert atmosphere; Large scale
2: thionyl chloride / 3 h / 50 °C
3: potassium carbonate / N,N-dimethyl-formamide / 1.25 h / 95 °C
4: sodium hydroxide / methanol / 3 h / 50 °C
5: Large scale
View Scheme
3-(cyclopropylmethoxy)-4-hydroxybenzoic acid
1243391-44-7

3-(cyclopropylmethoxy)-4-hydroxybenzoic acid

roflumilast
162401-32-3

roflumilast

Conditions
ConditionsYield
Multi-step reaction with 4 steps
1: thionyl chloride / 3 h / 50 °C
2: potassium carbonate / N,N-dimethyl-formamide / 1.25 h / 95 °C
3: sodium hydroxide / methanol / 3 h / 50 °C
4: Large scale
View Scheme
Multi-step reaction with 4 steps
1: thionyl chloride / 3 h / 50 °C
2: N,N-dimethyl-formamide / Heating
3: sodium hydroxide / methanol / 3 h / 50 °C
4: Large scale
View Scheme
3-cyclopropylmethoxy-4-hydroxybenzoic acid methyl ester

3-cyclopropylmethoxy-4-hydroxybenzoic acid methyl ester

roflumilast
162401-32-3

roflumilast

Conditions
ConditionsYield
Multi-step reaction with 3 steps
1: potassium carbonate / N,N-dimethyl-formamide / 1.25 h / 95 °C
2: sodium hydroxide / methanol / 3 h / 50 °C
3: Large scale
View Scheme
Multi-step reaction with 3 steps
1: N,N-dimethyl-formamide / Heating
2: sodium hydroxide / methanol / 3 h / 50 °C
3: Large scale
View Scheme
3-(cyclopropylmethoxy)-4-(difluoromethoxy)-benzoic acid methyl ester

3-(cyclopropylmethoxy)-4-(difluoromethoxy)-benzoic acid methyl ester

roflumilast
162401-32-3

roflumilast

Conditions
ConditionsYield
Multi-step reaction with 2 steps
1: sodium hydroxide / methanol / 3 h / 50 °C
2: Large scale
View Scheme
4-difluoromethoxy-3-hydroxybenzaldehyde
151103-08-1

4-difluoromethoxy-3-hydroxybenzaldehyde

roflumilast
162401-32-3

roflumilast

Conditions
ConditionsYield
Multi-step reaction with 4 steps
1.1: potassium carbonate; potassium iodide / acetone / 0.5 h / Inert atmosphere; Reflux
1.2: 12.5 h / 20 °C / Inert atmosphere; Reflux
2.1: aminosulfonic acid; sodium chlorite / water; acetonitrile / 5 h / 0 - 20 °C
3.1: thionyl chloride; N,N-dimethyl-formamide / toluene / 3 h / Reflux
4.1: sodium hydroxide / toluene / 2 h
4.2: 6 h / Reflux
View Scheme
Multi-step reaction with 4 steps
1.1: potassium carbonate; potassium iodide / dimethyl sulfoxide / 1 h / 70 °C
1.2: 4 h / 70 °C
2.1: acetic acid; aminosulfonic acid / 5 - 20 °C
3.1: dimethyl sulfoxide / 2 h / 20 °C
4.1: cesium fluoride / dimethyl sulfoxide / 3 h / 90 °C
4.2: 3 h / 90 - 95 °C
View Scheme
Multi-step reaction with 4 steps
1.1: potassium carbonate; potassium iodide / dimethyl sulfoxide / 1 h / 70 °C
1.2: 4 h / 70 °C
2.1: acetic acid; aminosulfonic acid / 5 - 20 °C
3.1: dimethyl sulfoxide / 3 h / 20 °C
4.1: cesium fluoride / dimethyl sulfoxide / 3 h / 90 °C
4.2: 6.5 h / 90 - 95 °C
View Scheme
3-(cyclopropylmethoxy)-4-(difluoromethoxy)-benzaldehyde
151103-09-2

3-(cyclopropylmethoxy)-4-(difluoromethoxy)-benzaldehyde

roflumilast
162401-32-3

roflumilast

Conditions
ConditionsYield
Multi-step reaction with 3 steps
1.1: aminosulfonic acid; sodium chlorite / water; acetonitrile / 5 h / 0 - 20 °C
2.1: thionyl chloride; N,N-dimethyl-formamide / toluene / 3 h / Reflux
3.1: sodium hydroxide / toluene / 2 h
3.2: 6 h / Reflux
View Scheme
Multi-step reaction with 3 steps
1: amberlyst 15 wet (9.0 g, 30percent w/w) / toluene / 20 °C / Inert atmosphere; Reflux
2: trifluoroacetic acid / toluene / 40 - 110 °C
3: sodium chlorite; acetic acid; 2-methyl-but-2-ene / water; acetonitrile / 2 h / 20 - 30 °C / Cooling with ice
View Scheme
Multi-step reaction with 3 steps
1.1: acetic acid; aminosulfonic acid / 5 - 20 °C
2.1: dimethyl sulfoxide / 2 h / 20 °C
3.1: cesium fluoride / dimethyl sulfoxide / 3 h / 90 °C
3.2: 3 h / 90 - 95 °C
View Scheme
3,5-dichloro-4-aminopyridine
22889-78-7

3,5-dichloro-4-aminopyridine

3-(cyclopropylmethoxy)-4-(difluoromethoxy)-benzaldehyde
151103-09-2

3-(cyclopropylmethoxy)-4-(difluoromethoxy)-benzaldehyde

roflumilast
162401-32-3

roflumilast

Conditions
ConditionsYield
Multi-step reaction with 2 steps
1: N,O-Bis(trimethylsilyl)trifluoroacetamide; toluene-4-sulfonic acid / acetonitrile / 48 h / Reflux
2: sodium chlorite; acetic acid; 2-methyl-but-2-ene / water; acetonitrile / 2 h / 20 - 30 °C / Cooling with ice
View Scheme
Multi-step reaction with 2 steps
1.1: trifluoroacetic acid; trimethyl orthoformate / toluene / 20 - 30 °C / Inert atmosphere; Reflux
1.2: 40 - 110 °C
2.1: sodium chlorite; acetic acid; 2-methyl-but-2-ene / water; acetonitrile / 3 h / 20 - 30 °C / Cooling with ice
View Scheme
C14H18F2O4
1454798-33-4

C14H18F2O4

roflumilast
162401-32-3

roflumilast

Conditions
ConditionsYield
Multi-step reaction with 2 steps
1: trifluoroacetic acid / toluene / 40 - 110 °C
2: sodium chlorite; acetic acid; 2-methyl-but-2-ene / water; acetonitrile / 2 h / 20 - 30 °C / Cooling with ice
View Scheme
3,4-dihydroxybenzaldehyde
139-85-5

3,4-dihydroxybenzaldehyde

roflumilast
162401-32-3

roflumilast

Conditions
ConditionsYield
Multi-step reaction with 5 steps
1.1: potassium carbonate / N,N-dimethyl-formamide / 20 - 85 °C
1.2: 8 - 10 h / Inert atmosphere
2.1: 1,8-diazabicyclo[5.4.0]undec-7-ene / tetrahydrofuran / 6 h / 75 - 80 °C
3.1: aminosulfonic acid; acetic acid / water / 5 - 10 °C
3.2: 1 h / 5 - 10 °C
4.1: thionyl chloride / tetrahydrofuran / 0.5 h / 20 - 45 °C
5.1: sodium hydride / tetrahydrofuran / 0.5 h
5.2: 1 h / 20 - 30 °C
View Scheme
Multi-step reaction with 4 steps
1.1: tetrabutylammonium hydrogen sulfide; sodium hydroxide / 3 h / 60 - 65 °C
2.1: potassium carbonate; potassium iodide; trimethylbenzylammonium bromide / tetrahydrofuran / 0 °C / Reflux
3.1: sodium chlorite; aminosulfonic acid / acetic acid; water / 1 h / 20 °C
4.1: 2-chloro-4,6-dimethoxy-1 ,3,5-triazine; 4-methyl-morpholine / dichloromethane / 3 h / 0 - 20 °C
4.2: 2 h
View Scheme
Multi-step reaction with 5 steps
1: sodium hydroxide / water / Heating
2: potassium carbonate / tetrahydrofuran / 14 h / Reflux
3: sodium chlorite; acetic acid; aminosulfonic acid / Cooling with ice
4: thionyl chloride / N,N-dimethyl-formamide; toluene / 3 h / 80 °C
5: tetrahydrofuran / 2.5 h / 0 - 10 °C
View Scheme
sodium 5-methyl-2-methoxyphenolate

sodium 5-methyl-2-methoxyphenolate

roflumilast
162401-32-3

roflumilast

Conditions
ConditionsYield
Multi-step reaction with 7 steps
1: potassium permanganate; sulfuric acid
2: thionyl chloride / N,N-dimethyl-formamide / Reflux
3: triethylamine / water / 3 °C
4: hydrogenchloride
5: sulfuric acid / 7 h / 140 °C / Inert atmosphere
6: hydrogen iodide / ethanol / 2 h
7: sulfuric acid / 7 h / 140 °C / Inert atmosphere
View Scheme
Na(1+)*C8H7O4(1-)

Na(1+)*C8H7O4(1-)

roflumilast
162401-32-3

roflumilast

Conditions
ConditionsYield
Multi-step reaction with 6 steps
1: thionyl chloride / N,N-dimethyl-formamide / Reflux
2: triethylamine / water / 3 °C
3: hydrogenchloride
4: sulfuric acid / 7 h / 140 °C / Inert atmosphere
5: hydrogen iodide / ethanol / 2 h
6: sulfuric acid / 7 h / 140 °C / Inert atmosphere
View Scheme
Na(1+)*C8H6ClO3(1-)

Na(1+)*C8H6ClO3(1-)

roflumilast
162401-32-3

roflumilast

Conditions
ConditionsYield
Multi-step reaction with 5 steps
1: triethylamine / water / 3 °C
2: hydrogenchloride
3: sulfuric acid / 7 h / 140 °C / Inert atmosphere
4: hydrogen iodide / ethanol / 2 h
5: sulfuric acid / 7 h / 140 °C / Inert atmosphere
View Scheme
C13H9Cl2N2O3(1-)*Na(1+)

C13H9Cl2N2O3(1-)*Na(1+)

roflumilast
162401-32-3

roflumilast

Conditions
ConditionsYield
Multi-step reaction with 4 steps
1: hydrogenchloride
2: sulfuric acid / 7 h / 140 °C / Inert atmosphere
3: hydrogen iodide / ethanol / 2 h
4: sulfuric acid / 7 h / 140 °C / Inert atmosphere
View Scheme
3-hydroxy-N-(3,5-dichloropyridin-4-yl)-4-methoxybenzamide
144036-24-8

3-hydroxy-N-(3,5-dichloropyridin-4-yl)-4-methoxybenzamide

roflumilast
162401-32-3

roflumilast

Conditions
ConditionsYield
Multi-step reaction with 3 steps
1: sulfuric acid / 7 h / 140 °C / Inert atmosphere
2: hydrogen iodide / ethanol / 2 h
3: sulfuric acid / 7 h / 140 °C / Inert atmosphere
View Scheme
3-(cyclopropylmethoxy)-N-(3,5-dichloropyridin-4-yl)-4-(methoxy)benzamide
159782-26-0

3-(cyclopropylmethoxy)-N-(3,5-dichloropyridin-4-yl)-4-(methoxy)benzamide

roflumilast
162401-32-3

roflumilast

Conditions
ConditionsYield
Multi-step reaction with 2 steps
1: hydrogen iodide / ethanol / 2 h
2: sulfuric acid / 7 h / 140 °C / Inert atmosphere
View Scheme
difluoromethyl alcohol
1426-06-8

difluoromethyl alcohol

3-(cyclopropylmethoxy)-N-(3,5-dichloropyridin-4-yl)-4-hydroxybenzamide

3-(cyclopropylmethoxy)-N-(3,5-dichloropyridin-4-yl)-4-hydroxybenzamide

roflumilast
162401-32-3

roflumilast

Conditions
ConditionsYield
With sulfuric acid at 140℃; for 7h; Inert atmosphere;20.76 g
2-chloro-1-methoxy-4-methylbenzene
22002-44-4

2-chloro-1-methoxy-4-methylbenzene

roflumilast
162401-32-3

roflumilast

Conditions
ConditionsYield
Multi-step reaction with 8 steps
1: sodium hydroxide / toluene / 360 °C / 150015 Torr
2: potassium permanganate; sulfuric acid
3: thionyl chloride / N,N-dimethyl-formamide / Reflux
4: triethylamine / water / 3 °C
5: hydrogenchloride
6: sulfuric acid / 7 h / 140 °C / Inert atmosphere
7: hydrogen iodide / ethanol / 2 h
8: sulfuric acid / 7 h / 140 °C / Inert atmosphere
View Scheme
4-(difluoromethoxy)benzoic acid
4837-20-1

4-(difluoromethoxy)benzoic acid

roflumilast
162401-32-3

roflumilast

Conditions
ConditionsYield
Multi-step reaction with 5 steps
1: bis(trichloromethyl) carbonate; triethylamine / toluene / 6 h / 90 °C
2: potassium tert-butylate / tetrahydrofuran / 3 h / 20 °C
3: trichlorophosphate / 21 h / 30 - 80 °C / Inert atmosphere
4: dihydrogen peroxide; sulfuric acid / methanol / 10 h / 20 - 30 °C
5: potassium carbonate / N,N-dimethyl-formamide / 2 h / 80 °C
View Scheme
roflumilast
162401-32-3

roflumilast

roflumilast N-oxide

roflumilast N-oxide

Conditions
ConditionsYield
With 3-chloro-benzenecarboperoxoic acid In chloroform at 20℃; for 44h; Product distribution / selectivity;93%
With dihydrogen peroxide; acetic acid at 70℃; for 6h; Temperature;82.7%
With 3-chloro-benzenecarboperoxoic acid In dichloromethane at 20℃; for 18h;
diethyl(imino)-λ6-sulfanone
92523-32-5

diethyl(imino)-λ6-sulfanone

roflumilast
162401-32-3

roflumilast

C21H23Cl2F2N3O4S

C21H23Cl2F2N3O4S

Conditions
ConditionsYield
With TEMPO; 3,6‐di‐tert‐butyl‐9‐mesityl‐10‐phenylacridin‐10‐ium tetrafluoroborate; oxygen In 1,2-dichloro-ethane at 37℃; for 14h; Sealed tube; Irradiation; regioselective reaction;62%
S-methyl-S-phenylsulfoximine
4381-25-3

S-methyl-S-phenylsulfoximine

roflumilast
162401-32-3

roflumilast

C24H21Cl2F2N3O4S

C24H21Cl2F2N3O4S

Conditions
ConditionsYield
With TEMPO; 3,6‐di‐tert‐butyl‐9‐mesityl‐10‐phenylacridin‐10‐ium tetrafluoroborate; oxygen In 1,2-dichloro-ethane at 37℃; for 14h; Sealed tube; Irradiation; regioselective reaction;57%
1-iminohexahydro-1λ6-thiopyran-1-oxide
35188-35-3

1-iminohexahydro-1λ6-thiopyran-1-oxide

roflumilast
162401-32-3

roflumilast

C22H23Cl2F2N3O4S

C22H23Cl2F2N3O4S

Conditions
ConditionsYield
With TEMPO; 3,6‐di‐tert‐butyl‐9‐mesityl‐10‐phenylacridin‐10‐ium tetrafluoroborate; oxygen In 1,2-dichloro-ethane at 37℃; for 14h; Sealed tube; Irradiation; regioselective reaction;53%
dimethylsulfoximine
1520-31-6

dimethylsulfoximine

roflumilast
162401-32-3

roflumilast

C19H19Cl2F2N3O4S

C19H19Cl2F2N3O4S

Conditions
ConditionsYield
With TEMPO; 3,6‐di‐tert‐butyl‐9‐mesityl‐10‐phenylacridin‐10‐ium tetrafluoroborate; oxygen In 1,2-dichloro-ethane at 37℃; for 14h; Sealed tube; Irradiation; regioselective reaction;51%
chloroacetonitrile
107-14-2

chloroacetonitrile

roflumilast
162401-32-3

roflumilast

N-cyanomethyl-N-(3,5-dichloropyrid-4-yl)-3-cyclopropylmethoxy-4-difluoromethoxybenzamide

N-cyanomethyl-N-(3,5-dichloropyrid-4-yl)-3-cyclopropylmethoxy-4-difluoromethoxybenzamide

Conditions
ConditionsYield
Stage #1: roflumilast With sodium hydride In N,N-dimethyl-formamide; mineral oil at 20℃; for 0.25h; Inert atmosphere;
Stage #2: chloroacetonitrile With sodium iodide In N,N-dimethyl-formamide; mineral oil at 20℃; for 2h; Inert atmosphere;
48%
cyclohexane
110-82-7

cyclohexane

roflumilast
162401-32-3

roflumilast

3-(cyclopropylmethoxy)-N-(3,5-dichloro-2,6-dicyclohexylpyridin-4-yl)-4-(difluoromethoxy)benzamide

3-(cyclopropylmethoxy)-N-(3,5-dichloro-2,6-dicyclohexylpyridin-4-yl)-4-(difluoromethoxy)benzamide

Conditions
ConditionsYield
With hydrogenchloride; dihydrogen peroxide In water; acetonitrile at 20℃; for 18h; Minisci Aromatic Substitution; Inert atmosphere; Irradiation; Green chemistry;48%
With hydrogenchloride; tetraethylammonium chloride In water; acetonitrile at 34 - 42℃; Electrochemical reaction; Irradiation; Inert atmosphere;44%
tert-butyl ((3-chloro-5,6-dicyanopyrazin-2-yl)oxy)carbamate

tert-butyl ((3-chloro-5,6-dicyanopyrazin-2-yl)oxy)carbamate

roflumilast
162401-32-3

roflumilast

tert-butyl (3,5-dichloro-4-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)benzamido)pyridin-2-yl)carbamate

tert-butyl (3,5-dichloro-4-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)benzamido)pyridin-2-yl)carbamate

Conditions
ConditionsYield
Stage #1: tert-butyl ((3-chloro-5,6-dicyanopyrazin-2-yl)oxy)carbamate; roflumilast With N,O-bis-(trimethylsilyl)-acetamide In 1,4-dioxane at 80℃; for 3h;
Stage #2: With acetic acid; zinc In 1,4-dioxane at 20℃; for 3h; chemoselective reaction;
42%
bromethyl methyl ether
13057-17-5

bromethyl methyl ether

roflumilast
162401-32-3

roflumilast

N-(3,5-dichloropyrid-4-yl)-N-methoxymethyl-3-cyclopropylmethoxy-4-difluoromethoxybenzamide

N-(3,5-dichloropyrid-4-yl)-N-methoxymethyl-3-cyclopropylmethoxy-4-difluoromethoxybenzamide

Conditions
ConditionsYield
With sodium hydride In N,N-dimethyl-formamide; mineral oil at 20℃; for 2h; Inert atmosphere;34%
3-(tert-butyldimethylsilyloxy)propyl bromide
89031-84-5

3-(tert-butyldimethylsilyloxy)propyl bromide

roflumilast
162401-32-3

roflumilast

N-(3,5-dichloropyrid-4-yl)-N-(3-tert-butyldimethylsilyloxypropan-1-yl)-3-cyclopropylmethoxy-4-difluoromethoxybenzamide

N-(3,5-dichloropyrid-4-yl)-N-(3-tert-butyldimethylsilyloxypropan-1-yl)-3-cyclopropylmethoxy-4-difluoromethoxybenzamide

Conditions
ConditionsYield
With sodium hydride In mineral oil at 20 - 70℃; for 12h; Inert atmosphere;31%
Chloroacetamide
79-07-2

Chloroacetamide

roflumilast
162401-32-3

roflumilast

N-carbamoylmethyl-N-(3,5-dichloropyrid-4-yl)-3-cyclopropylmethoxy-4-difluoromethoxybenzamide

N-carbamoylmethyl-N-(3,5-dichloropyrid-4-yl)-3-cyclopropylmethoxy-4-difluoromethoxybenzamide

Conditions
ConditionsYield
Stage #1: roflumilast With sodium hydride In N,N-dimethyl-formamide; mineral oil at 20℃; for 0.25h; Inert atmosphere;
Stage #2: Chloroacetamide With sodium iodide In N,N-dimethyl-formamide; mineral oil at 20℃; for 12h; Inert atmosphere;
16%
4-iodomethyl-2,2-dimethyl-[1,3]dioxolane
23737-52-2

4-iodomethyl-2,2-dimethyl-[1,3]dioxolane

roflumilast
162401-32-3

roflumilast

C23H24Cl2F2N2O5

C23H24Cl2F2N2O5

Conditions
ConditionsYield
With potassium hydroxide In dimethyl sulfoxide at 100℃; for 24h; Inert atmosphere;14%
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