Diisopropylcarbodiimide → (S)-N-(1-(3,5-dimethyl-1H-pyrazol-4-yl)ethyl)-2-(1-methyl-3-phenyl-4-(trifluoromethyl)-1H-pyrazolo[3,4-b]pyridin-6-yloxy)acetamide

Participants

Reaction Steps

A solution of (1-Methyl-3-phenyl-4-trifluoromethyl-1H-pyrazolo[3,4-b]pyridin-6-yloxy)-acetic acid (1.35 g, 3.843 mmol), DIC (727 mg, 5.769 mmol) and HOBt (674 mg, 4.996 mmol) in DMF (15 ml) was stirred at rt for 15 min. 1-(3,5-dimethyl-1H-pyrazole-4-yl)ethanamine (642 mg, 4.612 mmol) was added to the solution at rt and stirring was continued overnight at rt. After completion of the reaction, ice-cold water was added to the reaction mixture and the mixture was stirred for 10 min. The precipitate was collected by filtration and dried under vacuum. The racemic mixture was subjected to chiral preparative chromatographic separation to yield the enantiomeric pure title compound (165 mg) and the R enantiomer (165 mg, see example 1.62). [1H-NMR (CDCl3, 300 MHz) δ 7.62-7.48 (m, 5H), 6.99 (s, 1H), 6.55 (d, 1H), 5.33-4.92 (m, 3H), 4.1 (s, 3H), 2.25 (s, 6H), 1.55 (d, 3H); HPLC RtE=6.194 min. (98%); LCMS RtA=1.382, [M+H]+=473.1; Mp=145-147° C.]

Provenance & Evidence