Lithium Hydroxide → (R)-3-(5-cyano-3-fluoro-6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2-ylamino)-3-(1-methylcyclopentyl)propanoic acid

Participants

Reaction Conditions

Reaction Steps

To a solution of racemic methyl 3-(5-cyano-3-fluoro-6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2-ylamino)-3-(1-methylcyclopentyl)propanoate, 145a, (0.090 g, 0.204 mmol) in THF (30 mL) was added a solution of lithium hydroxide (0.035 g, 0.819 mmol) in H2O (10 mL). The reaction mixture was stirred at 70° C. overnight. The organic phase was removed under reduced pressure and the resulting residue was purified by preparatory HPLC. The appropriate HPLC fractions were extracted with EtOAc, and the solvent was removed under reduced pressure: 1H NMR (400 MHz, MeOD) δ 8.64 (dd, J=8.4, 2.4 Hz, 1H), 8.57 (s, 1H), 8.24 (d, J=4.4 Hz, 1H), 5.19 (d, J=8.7 Hz, 1H), 2.78 (qd, J=15.9, 6.6 Hz, 2H), 1.85-1.57 (m, 6H), 1.48 (dd, J=11.8, 6.0 Hz, 1H), 1.36 (dt, J=12.0, 6.0 Hz, 1H), 1.11 (s, 3H); LCMS Gradient 10-90%, 0.1% formic acid, 5 minutes, C18/ACN, Retention Time=3.21 minutes (M+H) 426.25.

Provenance & Evidence