T-BUTYL 2-CARBAMOTHIOYL-2-(3-(5-(4-CYANOPHENOXY)PYRIDIN-2-YL)-2-(2,4-DIFLUOROPHENYL)-3,3-DIFLUORO-2-HYDROXYPROPYL)HYDRAZINE-1-CARBOXYLATE AND PROCESSES OF PREPARATION
Provided herein is a process for the preparation of i-butyl 2-carbamothioyl-2-(3-(5-(4-cyanophenoxy)pyridin-2-yl)-2-(2,4-difluorophenyl)-3,3-difluoro-2-hydroxypropyl)hydrazine-1-carboxylate.
1 . A method of making a compound of Formula I comprising:
contacting a compound of Formula II
with an organic isothiocyanate, and a cleaving reagent.
2 . The method of claim 1 wherein the organic isothiocyanate is an acyl isothiocyanate or a silyl isothiocyanate.
3 . The method of claim 2 wherein the acyl isothiocyanate is benzoyl isothiocyanate.
4 . The method of claim 2 wherein the silyl isothiocyanate is trimethylsilyl isothiocyanate.
5 . The method of claim 1 wherein the cleaving reagent is selected from the group including hydrazine, ammonia, sodium methoxide, methylamine, a fluoride compound and an acid.
6 . The method of claim 1 wherein the contacting with the organic isothiocyanate is carried out between about −20° C. and about 100° C.
7 . The method of claim 1 wherein the contacting with the cleaving reagent is carried out between about −20° C. and about 100° C.
8 . The method of claim 1 further comprising the step of contacting the compound of Formula III
with t-butyl carbazate to prepare the compound of Formula II.
9 . The method of claim 8 further comprising a solvent selected from the group including methanol, ethanol, isopropanol, THF, acetonitrile, DMSO, DMF, and mixtures thereof.
10 . The method of claim 8 wherein the contacting with the t-butyl carbazate is carried out between about 25° C. and about 100° C.
11 . A compound selected from the group consisting of:
wherein R=benzoyl or Me 3 Si.