154127-42-1

Basic information

• Product Name: (4S)-1,1-dioxide-3,4-dihydro-4-hydroxy-2-
• Synonyms: (S)-2-(3-Methoxypropyl)-3,4-dihydro-2H-thieno[3,2-e][1,2]thiazine-4-ol-6-sulfonaMide-1,1- dioxide;BrinzolaMide Related CoMpound A;4-hydroxy-2-(3-Methoxypropyl)-3,4-dihydro-2H-thieno[3,2-e][1,2]thiazine-6-sulfonaMide 1,1-dioxide;(S)-4-Hydroxy-2-(3-methoxypropyl)-3,4-dihydro-2H-thieno-[3,2-e][1,2]thiazine-6-sulfonamide 1,1-di;2H-Thieno[3,2-e]-1,2-thiazine-6-sulfonaMide,3,4-dihydro-4-hydroxy-2-(3-Methoxypropyl)-, 1,1-dioxide, (4S)-;Brinzolamide Intermediate 1;154127-42-1;(4S)-1,1-dioxide-3,4-dihydro-4-hydroxy-2-(3-methoxypropyl)-2H-Thieno
• CAS NO: 154127-42-1
• Molecular Formula: C₁₀H₁₆N₂O₆S₃
• Molecular Weight: 356.43884
• EINECS: 1312995-182-4
• Mol File: 154127-42-1.mol

Chemical Properties

• Boiling Point: 612.4 °C at 760 mmHg
• Flash Point: 324.2 °C
• Appearance: /
• Density: 1.575 g/cm³
• Vapor Pressure: 7.49E-16mmHg at 25°C
• Refractive Index: 1.615
• Storage Temp.: Sealed in dry,Room Temperature
• Solubility: DMSO (Slightly), Methanol (Slightly)
• PKA: 9.53±0.40(Predicted)
• CAS DataBase Reference: (4S)-1,1-dioxide-3,4-dihydro-4-hydroxy-2-(CAS DataBase Reference)
• NIST Chemistry Reference: (4S)-1,1-dioxide-3,4-dihydro-4-hydroxy-2-(154127-42-1)
• EPA Substance Registry System: (4S)-1,1-dioxide-3,4-dihydro-4-hydroxy-2-(154127-42-1)

Safety Data

• Hazardous Substances Data: 154127-42-1(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
(4S)-1,1-dioxide-3,4-dihydro-4-hydroxy-2is used as a reactant for the preparation of Brinzolamide (AL-4862) [B677600], a topical carbonic anhydrase inhibitor. This application is due to its chemical properties that allow it to participate in the synthesis process, ultimately leading to the creation of a drug that can be used to treat certain medical conditions.

InChI:InChI=1/C10H16N2O6S3/c1-18-4-2-3-12-6-8(13)7-5-9(20(11,14)15)19-10(7)21(12,16)17/h5,8,13H,2-4,6H2,1H3,(H2,11,14,15)/t8-/m1/s1

Upstream product

• 154127-41-0 2H-thieno[3,2-e]-1,2-thiazin-6-sulphonamide, 3,4-dihydro-2-(3-methoxypropyl)-4-oxo-, 1,1-dioxide 
• 111-42-2 2,2'-iminobis[ethanol] 
• 1029324-91-1 (S)-3,4-dihydro-4-hydroxy-2-(3-methoxypropyl)-2H-thieno[3,2-e]-1,2-thiazine-1,1-dioxide 
• 1245550-91-7 C₁₀H₁₅BrN₂O₆S₃ 
• 160982-10-5 3-acetyl-5-chloro-2-thiophenesulfonamide 
• 160982-11-6 3-(2-Bromoacetyl)-5-chloro-thiophene-2-sulfonamide 
• 36157-40-1 3-acetyl-2,5-dichlorothiophene 
• 160982-16-1 (S)-3,4-dihydro-6-chloro-4-hydroxy-4H-thieno[3,2-e]-1,2-thiazine-1,1-dioxide 
• 160982-09-2 3-Acetyl-2-(phenylmethyl)thio-5-chlorothiophene 
• 160982-13-8 (S)-3,4-dihydro-6-chloro-4-hydroxy-2-(3-methoxypropyl)-4H-thieno[3,2-e]-1,2-thiazine 1,1-dioxide 

Downstream Products

• 138890-62-7 brinzolamide 

Relevant articles and documents

PROCESS FOR PREPARING BRINZOLAMIDE

The present invention refers to the preparation and purification of brinzolamide as well as to novel compounds useful in such processes.

Process for the preparation of (R)-(+)-4-(Ethylamino)-3,4-dihydro-2-(3-methoxypropyl)-2H-thieno[3,2-e]-1,2-thiazine-6-sulfonamide-1,1-dioxide.

Disclosed herein is an improved process for the preparation of (R)-(+)-4-(Ethylamino)-3,4-dihydro-2-(3-methoxypropyl)-2H-thieno[3,2-e]-1,2-thiazine-6-sulfonamide-1,1-dioxide (Brinzolamide) and novel intermediates thereof.

IMPROVED PROCESS FOR THE PREPARATION OF (R)-(+)-4-(ETHYIAMINO)-3,4-DIHYDRO-2-(3- METHOXYPROPYL)-2H-THIENO[3,2-E]-L,2-THIAZINE-6-SULFONAMIDE-L,L-DIOXIDE

Disclosed herein is an improved process for the preparation of (R)-(+)-4- (Ethylamino)-3,4-dihydro-2-(3-methoxypropyl)-2H-thieno[3,2-e]-1,2-thiazine-6- sulfonamide- 1,1 -dioxide (Brinzolamide) and novel intermediates thereof.

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.

Sulfonamides useful as carbonic anhydrase inhibitors

Sulfonamides and pharmaceutical compositions containing the compounds useful in controlling intraocular pressure are disclosed. Methods for controlling intraocular pressure through administration of the compositions are also disclosed.