ChemicalBook CAS DataBase List Brinzolamide

Brinzolamide synthesis

6synthesis methods

Product Name:Brinzolamide
CAS Number:138890-62-7
Molecular formula:C12H21N3O5S3
Molecular Weight:383.51

Brinzolamide synthesis method: using thiophene as raw material, 3-acetyl-2,5-dichlorothiophene (4) is obtained by chlorination and acetylation, and 4 is reacted with sodium benzyl sulfide to obtain 6,6, which is chlorinated and ammoniated. Chemical and oxidation reactions "one-pot" synthesis of 7, Carbon-based α-hydrobromination of 7 with Pyridinium tribromide gives 9,9 is asymmetrically reduced under the action of (+)-Ipc2BCl to obtain 11, which is then subjected to N-alkylation and sulfonamidation to generate (S)-3,4-dihydro-4-hydroxy-2-(3-methoxyl propyl)-2H-thieno[3,2-e]-1,2-thiazine-6-sulfonamide-1,1-dioxide, the sulfonamide group was protected with trimethyl orthoacetate to give 15 , first introduce p-toluenesulfonyl group and then replace it with ethylamino group, and remove the sulfonamide group protecting group to obtain brinzolamide. The synthesis of intermediate 4 in this route is convenient, and each step of the reaction does not require column chromatography, and the total yield is 13.4%.
Graphical Synthetic Routes of Olanzapine

150937-43-2
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138890-62-7
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$5.00/10mg

Yield:138890-62-7 500 g

Reaction Conditions:

with triethylamine in water; pH=7 - 8.5 at 25 - 30; for 2 h;

Steps:

1; 1 Example 1: Preparation of Brinzolamide free base from hydrochloride salt:
Example 1: Preparation of Brinzolamide free base from hydrochloride salt: Brinzolamide Hydrochloride (750 g) was dissolved in 5 volume water and filtered through celite bed to remove insoluble particles. Further, the solution was adjusted the pH to 7-8.5 with Triethylamine under stirring. Stirring was continued for additional 2 hours at 25 to 30°C followed by chilling the reaction mass at 0 to 5°C and stirred for 1 hour. The solids were filtered and washed with 1 volume of water. Wet cake was dried at 40°C under vacuum to yield Brinzolamide free base (500 g, HPLC purity: 98.5%).

References:

BIOCON LIMITED;KOTHAKONDA, Kiran Kumar;VENKATA, Srinivas Pullela;RAJMAHENDRA, Shanmughasamy;MHETRE, Sandeep Madhukar;CHANDAVARKAR, Arun WO2013/114397, 2013, A2 Location in patent:Page/Page column 7; 9