Method for producing 2-aminomethyl-4-cyano-thiazol
AssigneeAbbott GmbH & Co. KG
InventorThomas Pfeiffer
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Abstract
The invention relates to processes for preparing 2-aminomethyl-4-cyanothiazole and its salts of the formulae Ia and Ib in which n=1 or 2 and, for n=1, X is chloride, bromide, triflate and hydrogen sulfate and for n=2, X is sulfate, comprising the process step where the thioamide of the formula IV is stirred with a bromopyruvate of the formula V, in which R1 is branched or linear C1-4-alkyl in an alcohol R2OH in which R2 is branched or linear C1-8-alkyl, HO—CH2—CH2—, HO—CH2—CH2—CH2— or C1-4-alkyl- O—CH2—CH2— at from −5° C. to 40° C. until the conversion of the thioamide IV has essentially gone to completion, and to the compounds of the formulae Ia and Ib.
Claims8
A process for preparing 2-aminomethyl-4-cyanothiazole and its salts of the formulae 1a and 1b
- in which
- n=1 or 2 and,
- for n=1, X is chloride, bromide, triflate or hydrogen sulfate and
- for n=2, X is sulfate, comprising a) reacting a thioamide of the formula IV
- with a bromopyruvate of the formula V,
- in which R1 is branched or linear C1-4-alkyl in an alcohol R2OH in which R2 is branched or linear C1-8-alkyl, HO—CH2—CH2—, HO—CH2—CH2—CH2— or C1-4-alkyl-O—CH2—CH2— at from −5° C. to 40° C. to produce a thiazole carboxylic ester of the formula VI,
- in which R1 is branched or linear C1-4 alkyl;
- b) reacting the thiazole carboxylic ester of formula VI in an alcohol R2PH at from 0° C. to 40° C. with from 5 to 50 molar equivalents NH3 of an aqueous ammonia solution where R2 is as described above to produce a thiazole carboxamide of the formula VII
- c) dehydrating the amide VII to form BOC-protected 4-cyanothiazole of the formula VIII
- and d) removing the BOC protective group.
A process for preparing a compound of the formula VI
- in which R1 is branched or linear C1-4 alkyl where the thioamide of the formula IV where the thioamide of the formula IV
- is reacted with a bromopyruvate of the formula V,
- in an alcohol R2OH in which R2 is branched or linear C1-8-alkyl, HO—CH2—CH2—, HO—CH2—CH2—CH2— or C1-4-alkyl-O—CH2—CH2— at from −5° C. to 40° C.
A compound of the formula X
- in which R3 is a benzyloxycarbonyl, 9-fluorenylmethoxy-carbonyl, trifluoromethylacetyl, acetyl or benzoyl radical.
Dependencies are inferred from the claim text.