1,3-Thiazol-2-ylmethanol → Ethyl 5-trifluoromethyl-1-[(thiazol-2-yl)methyl]-1H-pyrrolo[2,3-b]pyridine-2-carboxylate

Reaction equation

[F:1][C:2]([F:18])([F:17])[C:3]1[CH:4]=[C:5]2[CH:11]=[C:10]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[NH:9][C:6]2=[N:7][CH:8]=1.[S:19]1[CH:23]=[CH:22][N:21]=[C:20]1[CH2:24]O.C(C=P(CCCC)(CCCC)CCCC)#N>>[F:18][C:2]([F:1])([F:17])[C:3]1[CH:4]=[C:5]2[CH:11]=[C:10]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[N:9]([CH2:24][C:20]3[S:19][CH:23]=[CH:22][N:21]=3)[C:6]2=[N:7][CH:8]=1

Participants

Reactant 3

HCID 27952131,3-Thiazol-2-ylmethanol

HCID 4622928Cyanomethylenetributylphosphorane

HCID 60146028ethyl 5-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridine-2-carboxylate

Product 1

HCID 66845785Ethyl 5-trifluoromethyl-1-[(thiazol-2-yl)methyl]-1H-pyrrolo[2,3-b]pyridine-2-carboxylateYield 83.1%

Procedure

This compound was prepared according to a process similar to that described in step 5.1. by reacting 390 mg (1.51 mmol) of ethyl 5-trifluoromethyl-1H-pyrrolo[2,3-b]pyridine-2-carboxylate (WO2008/107543) with 348 mg (3.02 mmol) of thiazol-2-ylmethanol in the presence of 0.92 g (3.826 mmol) of (cyanomethylene)-tributylphosphorane (CMBP). The reaction mixture is then purified by flash chromatography on a column of silica gel in a mixture of heptane and ethyl acetate to give 446 mg of the expected product in the form of an oil.