Method for producing 4-cyano-2-aminomethylthiazole
AssigneeAbbott GmbH & Ci, KG
InventorsMonika Knopp, Stefan Koser, Bernd Schaefer
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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, which comprises the process step where the aminonitrile of the formula II is stirred with a cysteine ester of the formula III, in which R1 is branched or linear C1-10-alkyl or where n=0, 1 or 2 and R2 is branched or linear C1-C10C10-alkyl or C1-C4-alkoxy or C1-C4-dialkylamino in an inert solvent in the presence of a base at from 0° C. to 80° C. until the reaction has essentially proceeded to completion, and to the compounds of the formulae Ia and Ib.
Claims16
A process for preparing a thiazolecarboxylic acid ester of formula V
- wherein R1 is branched or linear C1-10-alkyl or
- wherein n is 0, 1 or 2, and R2 is branched or linear C1-10-alkyl or C1-4-alkoxy or C1-4-dialkylamino, which comprises the step of preparing a thiazolidine of formula IV
- by stirring an aminonitrile of formula II
- with a cysteine ester of formula III
- in an inert solvent in the presence of a base at from 0° C. to 80° C. until the reaction has essentially proceeded to completion.
A compound of the formula Ia or 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.
A compound of the formula VII
The process defined in claim 16, wherein the thiazolecarboxamide of formula VI is filtered off as a solid.
The process defined in claim which further comprises dehydrating the thiazolecarboxamide of formula VI to obtain a BOC-protected 4-cyanothiazole of formula VII
- and subsequently removing the BOC protective group from the 4-cyanothiazole of formula VII to obtain the 2-aminomethyl-4-cyanothiazole of formula Ib or its salt of formula Ia.
A process for preparing 2-aminomethyl-4-cyanothiazole or its salt of formulae Ia and Ib
- wherein
- n is 1 or 2, and
- X is chloride, bromide, triflate or hydrogen sulfate when n is 1, and
- X is sulfate when n is 2,
- which comprises
- stirring an aminonitrile of formula II
- with a cysteine ester of formula III
- to obtain a thiazolidine of formula IV
- oxidizing the thiazolidine of formula IV in an inert solvent to obtain a thiazolecarboxylic acid ester of formula V
- stirring the thiazolecarboxylic acid ester of 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 0° C. to 40° C. with from 1 to 50 molar equivalents of NH3 until the reaction has essentially proceeded to completion, to obtain a thiazolecarboxamide of formula VI
- dehydrating the thiazolecarboxamide of formula VI to obtain a BOC-protected 4-cyanothiazole of formula VII
- and removing the BOC protective group from the 4-cyanothiazole of formula VII to obtain the 2-aminomethyl-4-cyanothiazole of formula Ib or its salt of formula Ia.
Dependencies are inferred from the claim text.