65002-17-7

Basic information

• Product Name: BUCILLAMINE
• Synonyms: sa96;thiobutarit;BUCILLAMINE;L-Cysteine, N-(2-mercapto-2-methyl-1-oxopropyl)-;N-(2-Mercaptoisobutyryl)cysteine;Tiobutarit;(R)-3-Mercapto-2-(2-Mercapto-2-MethylpropanaMido)propanoic acid;de-019
• CAS NO: 65002-17-7
• Molecular Formula: C₇H₁₃NO₃S₂
• Molecular Weight: 223.31
• Product Categories: Amino Acids & Derivatives;Chiral Reagents;Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 65002-17-7.mol

Chemical Properties

• Melting Point: 119-123°C
• Boiling Point: 438 °C at 760 mmHg
• Flash Point: 218.7 °C
• Appearance: /
• Density: 1.3934 (rough estimate)
• Vapor Pressure: 6.77E-09mmHg at 25°C
• Refractive Index: 1.6370 (estimate)
• Storage Temp.: Hygroscopic, -20?C Freezer, Under Inert Atmosphere
• Solubility: DMSO (Very Slightly), Ethanol (Slightly), Methanol (Slightly), Water (Slightly)
• PKA: 3.01±0.10(Predicted)
• Stability: Air Sensitive, Hygroscopic, Unstable in Solution
• CAS DataBase Reference: BUCILLAMINE(CAS DataBase Reference)
• NIST Chemistry Reference: BUCILLAMINE(65002-17-7)
• EPA Substance Registry System: BUCILLAMINE(65002-17-7)

Safety Data

• Hazardous Substances Data: 65002-17-7(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
Bucillamine is used as an antirheumatic agent for the treatment of rheumatoid arthritis. Its immunomodulatory properties and ability to inhibit collagenase activity and inactivate rheumatoid factor contribute to its effectiveness in managing the symptoms and progression of the disease.

Originator

Santen (Japan)

Manufacturing Process

Preparation of N-(2-benzylmercaptoisobutyryl)-S-benzyl-L-cysteine: 1). 73.9 g of S-benzyl-L-cysteine were dissolved in 700 ml of 1 N sodium hydroxide solution. The solution was cooled in an ice bath and stirred. 2- Benzylmercaptoisobutyryl chloride, which was obtained by reacting 63.1 g of 2-benzylmercaptoisobutyric acid with 39.3 g of thionyl chloride, was added dropwise to this solution. The resulting mixture was then stirred for one hour, acidified with hydrochloric acid and extracted with ethyl acetate. The extract was washed with water, dried over sodium sulfate and evaporated to dryness. The residue was chromatographed on silica gel with benzene/ethylacetate (1:1) as an eluant. The eluate was evaporated to dryness and an oily residue weighing 46.9 g, representing a yield of 74%, was obtained. 2). The obtained in (1) above were dissolved in 500 ml of liquid ammonia and 21.1 g of metallic sodium were added slowly with stirring. After completion of reaction, 59.4 g of ammonium chloride were added and thereafter the ammonia was removed by distillation. Water was added to the residue to dissolve the solid. The resulting water layer was separated, washed with ethyl acetate, and acidified with hydrochloric acid under cooling. The precipitates thus obtained were extracted with ethyl acetate. The extract was washed with water, dried over sodium sulfate and evaporated to dryness. The product weighed 43.6 g, representing a yield of 88%. After recrystallization from ethyl acetate, the desired compound, melting at 139°-140°C, was obtained. [α]D 25=+32.3° (c=1.0, ethanol).

Therapeutic Function

Antirheumatic, Immunomodulator

InChI:InChI=1/C7H13NO3S2/c1-7(2,13)6(11)8-4(3-12)5(9)10/h4,12-13H,3H2,1-2H3,(H,8,11)(H,9,10)/t4-/m0/s1

Synthetic route

S-benzyl-N-(S-benzyl-2-mercapto-2-methylpropanoyl)-L-cysteine (65002-16-6) → bucillamine (65002-17-7)

Conditions	Yield
With ammonia; sodium	81%

L-Cysteine (52-90-4) + 2-mercapto-2-methylpropanoic acid (4695-31-2) → bucillamine (65002-17-7)

Conditions	Yield
With potassium carbonate; dicyclohexyl-carbodiimide 1.) EtOAc, r.t., 1 h; 2.) EtOAc, MeOH, water, r.t., 4 h; Yield given. Multistep reaction;

bucillamine (65002-17-7) + methyl iodide (74-88-4) → 2-methylmercapto-isobutyroyl-l-S-methylcysteine (74407-28-6)

Conditions	Yield
With potassium carbonate for 1h; Ambient temperature;	75%

bucillamine (65002-17-7) → S-methyl-N-<2-methyl-2-(methylthio)propanoyl>-L-cysteine methyl ester (87122-78-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: 75 percent / 2 N potassium carbonate / 1 h / Ambient temperature 2: diethyl ether View Scheme

diazomethane (186581-53-3, 908094-01-9) + bucillamine (65002-17-7) → N-(2-Mercapto-2-Methylpropionyl)-L-Cysteine Methyl Ester (124775-79-7)

Conditions	Yield
With acetic acid	1.0 g(94%)

trityl chloride (76-83-5) + bucillamine (65002-17-7) → N-(2-Mercapto-2-Methylpropionyl)-S-Trityl-L-Cysteine (124775-71-9)

Conditions	Yield
In N-methyl-acetamide	14.2 g(60%)

copper(ll) sulfate pentahydrate + bucillamine (65002-17-7) → (4R)-tetrahydro-7,7-dimethyl-6-oxo-3H-1,2,5-dithiazepine-4-carboxylic acid (82017-48-9)

Conditions	Yield
	0.45 g (45%)

bucillamine (65002-17-7) → S,S'-dinitrosobucillamine (1622079-83-7)

Conditions	Yield
With sodium nitrite Acidic conditions;

bucillamine (65002-17-7) + (2,5-dioxopyrrolidin-1- yl)oxycarbonyloxymethyl acetate → (2R)-3-(acetoxymethoxycarbonylsulfanyl)-2-[[2-(acetoxymethoxycarbonylsulfanyl)-2-methylpropanoyl]amino]propanoic acid

Conditions	Yield
at 20℃;

Upstream product

• 52-90-4 L-Cysteine 
• 4695-31-2 2-mercapto-2-methylpropanoic acid 
• 65002-16-6 S-benzyl-N-(S-benzyl-2-mercapto-2-methylpropanoyl)-L-cysteine 

Downstream Products

• 82017-48-9 (4R)-tetrahydro-7,7-dimethyl-6-oxo-3H-1,2,5-dithiazepine-4-carboxylic acid 
• 74407-28-6 2-methylmercapto-isobutyroyl-l-S-methylcysteine 

Relevant articles and documents

Cysteine derivatives

This invention relates to the compounds: N-(mercaptoacy)-cysteine represented by the following formula wherein Z is selected from the group consisting of CH3 --CH3)2 C2)2 2 , acting as agents for the liquefaction of sputum, intermediate therefor and a process for manufacture thereof STR1