147254-64-6

Basic information

• Product Name: (3R)-2'-(4-Bromo-2-fluorobenzyl)spiro[pyrrolidine-3,4'-1'H-pyrrolo[1,2-a]pyrazine]-1',2,3',5(2'H)-tetraone
• Synonyms: (3R)-2'-(4-Bromo-2-fluorobenzyl)spiro[pyrrolidine-3,4'-1'H-pyrrolo[1,2-a]pyrazine]-1',2,3',5(2'H)-tetraone;Ranirestat;AS 3201;AS-3201;Spiro[pyrrolidine-3,4'(1'H)-pyrrolo[1,2-a]pyrazine]-1',2,3',5(2'H)-tetrone,2'-[(4-broMo-2-fluorophenyl)Methyl]-, (3R)-;Ranirestat,AS-3201;Raniestat
• CAS NO: 147254-64-6
• Molecular Formula: C₁₇H₁₁BrFN₃O₄
• Molecular Weight: 420.1893432
• Mol File: 147254-64-6.mol
• Article Data: 6

Chemical Properties

• Melting Point: 192-193℃
• Boiling Point: 702.7°Cat760mmHg
• Flash Point: 378.8°C
• Appearance: /
• Density: 1.83
• Storage Temp.: Sealed in dry,Store in freezer, under -20°C
• PKA: 10.48±0.20(Predicted)
• CAS DataBase Reference: (3R)-2'-(4-Bromo-2-fluorobenzyl)spiro[pyrrolidine-3,4'-1'H-pyrrolo[1,2-a]pyrazine]-1',2,3',5(2'H)-tetraone(CAS DataBase Reference)
• NIST Chemistry Reference: (3R)-2'-(4-Bromo-2-fluorobenzyl)spiro[pyrrolidine-3,4'-1'H-pyrrolo[1,2-a]pyrazine]-1',2,3',5(2'H)-tetraone(147254-64-6)
• EPA Substance Registry System: (3R)-2'-(4-Bromo-2-fluorobenzyl)spiro[pyrrolidine-3,4'-1'H-pyrrolo[1,2-a]pyrazine]-1',2,3',5(2'H)-tetraone(147254-64-6)

Safety Data

• Hazardous Substances Data: 147254-64-6(Hazardous Substances Data)

Usage

Description

(3R)-2'-(4-Bromo-2-fluorobenzyl)spiro[pyrrolidine-3,4'-1'H-pyrrolo[1,2-a]pyrazine]-1',2,3',5(2'H)-tetraone is a complex organic compound with a unique molecular structure. It is characterized by its spiro-linked pyrrolidine and pyrrolo[1,2-a]pyrazine rings, with a 4-bromo-2-fluorobenzyl group attached to the 2' position. (3R)-2'-(4-Bromo-2-fluorobenzyl)spiro[pyrrolidine-3,4'-1'H-pyrrolo[1,2-a]pyrazine]-1',2,3',5(2'H)-tetraone exhibits a range of biological activities and potential applications across various industries.

Uses

Used in Pharmaceutical Industry:
(3R)-2'-(4-Bromo-2-fluorobenzyl)spiro[pyrrolidine-3,4'-1'H-pyrrolo[1,2-a]pyrazine]-1',2,3',5(2'H)-tetraone is used as a therapeutic agent for the treatment of various medical conditions. Its specific application reason is due to its ability to modulate biological targets and pathways, potentially leading to the development of novel drugs for the treatment of diseases such as cancer, neurological disorders, and inflammatory conditions.
Used in Chemical Research:
In the field of chemical research, (3R)-2'-(4-Bromo-2-fluorobenzyl)spiro[pyrrolidine-3,4'-1'H-pyrrolo[1,2-a]pyrazine]-1',2,3',5(2'H)-tetraone serves as a valuable compound for studying its chemical properties, reactivity, and potential use in the synthesis of other complex molecules. Its unique structure allows researchers to explore new synthetic routes and develop innovative methodologies for the preparation of related compounds with potential applications in various fields.
Used in Material Science:
(3R)-2'-(4-Bromo-2-fluorobenzyl)spiro[pyrrolidine-3,4'-1'H-pyrrolo[1,2-a]pyrazine]-1',2,3',5(2'H)-tetraone may also find applications in the field of material science, particularly in the development of novel materials with specific properties. Its unique molecular structure could be exploited to design materials with tailored characteristics, such as improved mechanical strength, thermal stability, or optical properties, depending on the application requirements.

Synthetic route

(S)-methyl 4-(2-amino-2-oxoethyl)-2-(4-bromo-2-fluorobenzyl)-1,3-dioxo-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazine-4-carboxylate (1211939-75-1) → ranirestat (147254-64-6)

Conditions	Yield
With lithium hexamethyldisilazane In tetrahydrofuran at -78℃; Inert atmosphere;	95%

4-bromo-2-fluorobenzylamine (112734-22-2) + R-(-)-3-ethoxycarbonyl-3-(2-(trichloroacetyl)pyrrol-1-yl)pyrrolidin-2,5-dione (159213-26-0) → ranirestat (147254-64-6)

Conditions	Yield
In N,N-dimethyl-formamide at 20℃; for 5h;	71%
With triethylamine In N,N-dimethyl-formamide at 20℃;	65%
With triethylamine In N,N-dimethyl-formamide at 20℃; for 8h;	65%

(2R)-2-ethoxycarbonyl-2-(pyrrol-1-yl)succinimide diisopropylamine salt (1000784-39-3) + 4-bromo-2-fluorobenzylamine (112734-22-2) → ranirestat (147254-64-6)

Conditions	Yield
Stage #1: (2R)-2-ethoxycarbonyl-2-(pyrrol-1-yl)succinimide diisopropylamine salt With sulfuric acid; water In ethyl acetate Stage #2: With trifluoroacetyl chloride In ethyl acetate for 6h; Heating / reflux; Stage #3: 4-bromo-2-fluorobenzylamine With water; sodium hydrogencarbonate; diisopropylamine more than 3 stages;	58%

(4-bromo-2-fluorophenyl)methanamine hydrochloride + R-(-)-3-ethoxycarbonyl-3-(2-(trichloroacetyl)pyrrol-1-yl)pyrrolidin-2,5-dione (159213-26-0) → ranirestat (147254-64-6)

Conditions	Yield
With triethylamine In N,N-dimethyl-formamide for 16h; Ambient temperature;	45%

(R)-ethyl-3-amino-2,5-dioxopyrrolidine-3-carboxylate (159213-18-0) → ranirestat (147254-64-6)

Conditions	Yield
Multi-step reaction with 3 steps 1: 72.4 percent / AcOH / 1.5 h / 70 °C 2: 91.9 percent / CHCl3 / 16 h / Heating 3: 45 percent / Et3N / dimethylformamide / 16 h / Ambient temperature View Scheme
Multi-step reaction with 3 steps 1.1: water / Heating 1.2: 22; 13 / 12 h / 40 °C 2.1: 10 h / 80 °C 3.1: N,N-dimethyl-formamide / 5 h / 20 °C View Scheme

ethyl 2,5-dioxo-3-(1H-pyrrol-1-yl)pyrrolidine-3-carboxylate (159213-19-1) → ranirestat (147254-64-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: 91.9 percent / CHCl3 / 16 h / Heating 2: 45 percent / Et3N / dimethylformamide / 16 h / Ambient temperature View Scheme
Multi-step reaction with 2 steps 1: ethyl acetate / Reflux 2: triethylamine / N,N-dimethyl-formamide / 8 h / 20 °C View Scheme

ethyl 3-benzyloxycarbonylamino-2,5-dioxopyrrolidine-3-carboxylate (147194-10-3) → ranirestat (147254-64-6)

Conditions	Yield
Multi-step reaction with 5 steps 2: 95.9 percent / H2 / 5percent Pd/C / ethanol / 40 - 50 °C / 760 Torr 3: 72.4 percent / AcOH / 1.5 h / 70 °C 4: 91.9 percent / CHCl3 / 16 h / Heating 5: 45 percent / Et3N / dimethylformamide / 16 h / Ambient temperature View Scheme

(R)-2-benzyloxycarbonylamino-2-ethoxycarbonylsuccinimide (159213-17-9) → ranirestat (147254-64-6)

Conditions	Yield
Multi-step reaction with 4 steps 1: 95.9 percent / H2 / 5percent Pd/C / ethanol / 40 - 50 °C / 760 Torr 2: 72.4 percent / AcOH / 1.5 h / 70 °C 3: 91.9 percent / CHCl3 / 16 h / Heating 4: 45 percent / Et3N / dimethylformamide / 16 h / Ambient temperature View Scheme

ethyl (R)-3-hydrazinyl-2,5-dioxopyrrolidine-3-carboxylate hydrochloride (952656-32-5) → ranirestat (147254-64-6)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: hydrogen / nickel / ethanol / 42 h / 20 °C 2.1: water / Heating 2.2: 22; 13 / 12 h / 40 °C 3.1: 10 h / 80 °C 4.1: N,N-dimethyl-formamide / 5 h / 20 °C View Scheme

R-(-)-3-ethoxycarbonyl-3-(N,N'-di(tert-butoxycarbonyl)hydrazino)pyrrolidin-2,5-dione hydrochloride → ranirestat (147254-64-6)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: hydrogenchloride / toluene / 2.5 h / 0 °C 2.1: hydrogen / nickel / ethanol / 42 h / 20 °C 3.1: water / Heating 3.2: 22; 13 / 12 h / 40 °C 4.1: 10 h / 80 °C 5.1: N,N-dimethyl-formamide / 5 h / 20 °C View Scheme

uridine diphosphoglucuronic acid (2616-64-0, 7305-43-3, 50722-58-2) + ranirestat (147254-64-6) → AS-3201 N-glucuronide

Conditions	Yield
With human liver microsomes; magnesium chloride In various solvents at 37℃; for 20h; pH=7.1; Enzyme kinetics; Further Variations:; Reagents;

diphosphoric acid 1''-β-D-[1'']glucopyranosyl ester 2-(uridin-5'-yl)ester (133-89-1, 2956-16-3, 7307-71-3, 7349-77-1, 16375-64-7, 16375-65-8, 16414-46-3, 17012-87-2, 25318-68-7, 78391-94-3, 99020-05-0, 99945-86-5) + ranirestat (147254-64-6) → AS-3201 N-glucoside

Conditions	Yield
With human liver microsomes; magnesium chloride In various solvents at 37℃; for 2h; pH=7.1; Enzyme kinetics; Further Variations:; Reagents;

Upstream product

• 159213-26-0 R-(-)-3-ethoxycarbonyl-3-(2-(trichloroacetyl)pyrrol-1-yl)pyrrolidin-2,5-dione 
• 112734-22-2 4-bromo-2-fluorobenzylamine 
• 159213-18-0 (R)-ethyl-3-amino-2,5-dioxopyrrolidine-3-carboxylate 
• 159213-19-1 ethyl 2,5-dioxo-3-(1H-pyrrol-1-yl)pyrrolidine-3-carboxylate 
• 147194-10-3 ethyl 3-benzyloxycarbonylamino-2,5-dioxopyrrolidine-3-carboxylate 
• 159213-17-9 (R)-2-benzyloxycarbonylamino-2-ethoxycarbonylsuccinimide 
• 1000784-39-3 (2R)-2-ethoxycarbonyl-2-(pyrrol-1-yl)succinimide diisopropylamine salt 
• 1211939-75-1 (S)-methyl 4-(2-amino-2-oxoethyl)-2-(4-bromo-2-fluorobenzyl)-1,3-dioxo-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazine-4-carboxylate 
• 952656-32-5 ethyl (R)-3-hydrazinyl-2,5-dioxopyrrolidine-3-carboxylate hydrochloride 

Relevant articles and documents

En route to an efficient catalytic asymmetric synthesis of AS-3201

A catalytic asymmetric synthesis of AS-3201 via catalytic asymmetric amination with a novel lanthanum-amide complex is described. The amination reaction proceeded efficiently with as little as 1 mol % of catalyst loading, allowing for an efficient access to the key intermediate for the synthesis of AS-3201, a potent aldose reductase inhibitor. Copyright

A concise enantioselective synthesis of (-)-ranirestat

Chemical Equation Presented A concise enantioselective synthesis of the potent aldose reductase inhibitor ranirestat (1) is reported. The synthesis was accomplished employing inexpensive, commercially available starting materials. A palladium-catalyzed asymmetric allylic alkylation (Pd-AAA) of malonate 4 was utilized as a key transformation to construct the tetrasubstituted chiral center in the target.

3-HYDRAZINO-2,5-DIOXOPYRROLIDINE-3-CARBOXYLATES, PROCESS FOR PRODUCTION OF THE SAME, AND USE OF THE SAME

The present invention provides 3-hydrazino-2,5-dioxopyrrolidine-3-carboxylates of the formula (I): wherein R1 is a C1-6 alkyl group, etc., R2 is a hydrogen atom or a COOR3 group, wherein R3 is a tert-C4-6 alkyl group, a 2,2,2-trichloroethyl group or a benzyl group in which the benzene ring moiety may be optionally substituted by one or two atoms or groups independently selected from the group consisting of a halogen atom, a C1-4 alkyl group, a C1-4 alkoxy group, a cyano group and a nitro group, and a salt thereof, which are useful as a novel intermediate for preparing tetrahydropyrrolo[1,2-a]pyrazin-4-spiro-3′-pyrrolidine derivatives such as Ranirestat being promising therapeutic agents for diabetic complications in a short process and in an economically advantageous and safe manner, and the process for preparing the same.