160982-13-8

Basic information

• Product Name: (S)-6-Chloro-2-(3-methoxypropyl)-3,4-dihydro-2H-thieno[3,2-e][1,2]thiazin-4-ol 1,1-dioxide
• Synonyms: (4S)-6-Chloro-3,4-dihydro-2-(3-methoxypropyl)-2H-thieno[3,2-e]-1,2-thiazin-4-ol 1,1-Dioxide;(S)-6-Chloro-3,4-dihydro-2-(3-Methoxypropyl)-2H-thieno[3,2-e]-1,2-thiazin-4-ol 1,1-Dioxide;(S)-6-Chloro-4-hydroxy-2-(3-methoxypropyl)-3,4-dihydro-2H-thieno[3,2-e][1,2]thiazine 1,1-dioxide;Brinzolamide impurity D;(S)-6-Chloro-4-hydroxy-2-(3-methoxypropyl)-3,4-dihydro-2H-thieno[3,2-e][1,2]thiazine 1,1-dioxi;(S)-6-Chloro-2-(3-methoxypropyl)-3,4-dihydro-2H-thieno[3,2-e][1,2]thiazin-4-ol 1,1-dioxide
• CAS NO: 160982-13-8
• Molecular Formula: C₁₀H₁₄ClNO₄S₂
• Molecular Weight: 311.81
• Product Categories: Chiral Reagents;Intermediates & Fine Chemicals;Pharmaceuticals;Sulfur & Selenium Compounds
• Mol File: 160982-13-8.mol
• Article Data: 1

Chemical Properties

• Boiling Point: 466.142 °C at 760 mmHg
• Flash Point: 235.714 °C
• Appearance: /
• Density: 1.490
• Storage Temp.: 2-8°C
• Solubility: Chloroform (Slightly), Methanol (Slightly)
• PKA: 12.52±0.20(Predicted)
• CAS DataBase Reference: (S)-6-Chloro-2-(3-methoxypropyl)-3,4-dihydro-2H-thieno[3,2-e][1,2]thiazin-4-ol 1,1-dioxide(CAS DataBase Reference)
• NIST Chemistry Reference: (S)-6-Chloro-2-(3-methoxypropyl)-3,4-dihydro-2H-thieno[3,2-e][1,2]thiazin-4-ol 1,1-dioxide(160982-13-8)
• EPA Substance Registry System: (S)-6-Chloro-2-(3-methoxypropyl)-3,4-dihydro-2H-thieno[3,2-e][1,2]thiazin-4-ol 1,1-dioxide(160982-13-8)

Safety Data

• Hazardous Substances Data: 160982-13-8(Hazardous Substances Data)

Usage

Chemical Properties

Brown Oil

Uses

An intermediate in the preparation of Brinzolamide

Upstream product

• 160982-09-2 3-Acetyl-2-(phenylmethyl)thio-5-chlorothiophene 
• 160982-16-1 (S)-3,4-dihydro-6-chloro-4-hydroxy-4H-thieno[3,2-e]-1,2-thiazine-1,1-dioxide 
• 7239-41-0 4,4'-dibromo-di-n-butyl ether 
• 36157-40-1 3-acetyl-2,5-dichlorothiophene 
• 160982-11-6 3-(2-Bromoacetyl)-5-chloro-thiophene-2-sulfonamide 
• 160982-10-5 3-acetyl-5-chloro-2-thiophenesulfonamide 

Downstream Products

• 138890-62-7 brinzolamide 
• 154127-42-1 (S)-3,4-dihydro-4-hydroxy-2(3-methoxypropyl)-4H-thieno[3,2-e]-1,2-thiazine-6-sulfonamide-1,1-dioxide 
• 138890-50-3 brinzolamide 

Relevant articles and documents

Enantioselective synthesis of brinzolamide (AL-4862), a new topical carbonic anhydrase inhibitor. The "DCAT Route" to thiophenesulfonamides

A large scale synthesis of the topical carbonic anhydrase inhibitors AL-4623A (13a-HCl) and AL-4862 (13b) from 3-acetyl-2,5-dichlorothiophene ("DCAT", 1) is described. Reaction of 1 with NaSBn gave thioether 2, which was converted via sulfenyl chloride 3 and sulfenamide 5 to sulfonamide 6. Bromination of 6 gave bromo ketone 7, which upon reduction with (+)-B-chlorodiisopinocampheylborane and cyclization of the resulting bromohydrin produced S thieno[3,2-e]-1,2-thiazine 8a (96% ee) after chromatography. Treatment of 8a in THF with -BuLi at -70 °C resulted in Li-Cl exchange. Reaction of the thienyllithium with SO2 and hydroxylamine O-sulfonic acid afforded bis-sulfonamide 11a. Protection of lia as the acetimidate 12a, followed by tosylation and animation, gave R amine 13a. The synthesis of 13b proceeded via primary sulfonamide 16, which was brominated, reduced, and cyclized to give S thieno[3,2-e]-1,2-thiazine 18 (>98% ee). By virtue of the ionizable NH, 18 was separable from reduction byproducts by base extraction. Alkylation of 18 with 3-bromopropyl methyl ether afforded 8b, which was converted as above, via lib, to AL-4862 (13b). These procedures provided multihundred gram lots of 13a and 13b.