Process to prepare ethyl 4-methyl-2-(4-(2-methylpropyloxy)-3-cyanophenyl)-5-thiazolecarboxylate
AssigneeNatco Pharma Limited
InventorsAmala Kompella, Venue Gopala Krishna Gampa, Kali Satya Bhujanga Rao Adibhatla, Venkaiah Chowdary Nannapaneni
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Abstract
Disclosed is a process for the preparation of Ethyl 4-methyl-2-(4-(2-methylpropyloxy)-3-cyanophenyl)-5-thiazolecarboxylate (I) the key intermediate for the preparation of [2-[3-cyano-4-(2-Methyl-propoxy)phenyl]-4-methyl-5-thiazole carboxylic acid (Febuxostat, I(A)) is approved under the trademark Uloric® by the US Food and Drug Administration for the treatment of hyperuricemia and gouty arthritis.
Claims9
Improved process to prepare for the preparation of Ethyl 4-methyl-2-(4-(2-methylpropyloxy)-3-cyanophenyl)-5-thiazolecarboxylate of the formula-(I) as hydrochloride salt
- Comprising the following steps:
- a. Reaction of 3-bromo-4-hydroxy-benzaldehyde(XVI) with hydroxylamine and sodium formate in refluxing formic acid affords 3-bromo-4-hydroxy-benzonitrile (XVII).
- b. Treatment of compound (XVII) with thioacetamide giving rise to 3-bromo-4-hydroxy-thiobenzamide (XVIII).
- c. Cyclization of compound (XVIII) with 2-chloroacetoacetic acid ethyl ester affording 2-(3-bromo-4-hydroxyphenyl)-4-methylthiazole-5-carboxylic acid ethyl ester(XIX).
- d. Alkylation of compound (XIX) with isobutyl bromide gives 2-(3-bromo-4-isobutoxyphenyl)-4-methylthiazole-5-carboxylic acid ethyl ester(XX).
- e. Compound XX on cyanation with cuprous cyanide affords Ethyl 4-methyl-2-(4-(2-methylpropyloxy)-3-cyanophenyl)-5-thiazolecarboxylate(I).
- f. Purification of compound I by forming hydrochloride salt I—HCl in acetone medium
A method of preparing ethyl 4-methyl-2-(4-(2-methylpropyloxy)-3-cyanophenyl)-5-thiazolecarboxylate of formula (I) as hydrochloride salt essentially as in example-1
Dependencies are inferred from the claim text.