Lithium hydroxide, monohydrate → 2-(2-(2-(2-((6-(1-(tert-Butoxycarbonyl)piperidin-4-yl)pyridin-3-yl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetic acid

Participants

Reaction Conditions

Reaction Steps

LiOH.H2O (297 mg, 7.1 mmol) was added to a stirred solution of tert-butyl 4-(5-((4-(2-(2-methoxy-2-oxoethyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)pyridin-2-yl)piperidine-1-carboxylate (A45) (85 mg, 0.14 mmol) in H2O (2 mL) and THF (20 mL) and the resulting mixture heated at 40° C. for 18 hours. The volatiles were removed in vacuo and the residue was partitioned between EtOAc (100 mL), and aqueous 2 M HCl (50 mL). The layers were separated and the organics washed with water (100 mL), brine (50 mL) and dried over MgSO4. The volatiles were removed in vacuo to give the title compound A46 as an orange foam (74 mg, 89%); 1H NMR (400 MHz, d4-MeOH) δ 9.00 (d, J=1.8 Hz, 1H), 8.66 (s, 1H), 8.36 (dd, J=8.7, 2.6 Hz, 1H), 7.54 (d, J=8.7 Hz, 1H), 7.28-7.10 (m, 4H), 4.25 (d, J=13.4 Hz, 2H), 3.72 (s, 2H), 3.19-3.09 (m, 4H), 3.07-2.83 (m, 3H), 1.94 (d, J=12.7 Hz, 2H), 1.72 (m, 2H), 1.48 (s, 9H). LCMS-A: rt 5.707 min; m/z 586 [M+H]+.

Provenance & Evidence