Lithium Hydroxide → 1-(3-(5 (4-(Difluoromethoxy)phenyl)pyrimidin-2-ylamino)benzyl)piperidine-4-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

To a solution of 3-(5-(4-(difluoromethoxy)phenyl)pyrimidin-2-ylamino)benzyl methanesulfonate 37 (0.050 mmol) in anhydrous DMF (1 mL) is added methyl piperidine-4-carboxylate (0.10 mmol) and the solution is heated at 100° C. for 8 h. After the reaction is complete, the mixture is diluted with THF:MeOH:H2O (3:2:1, 5 mL). To the reaction mixture is added 6N LiOH (0.30 mmol). The reaction is stirred at rt for 1 h. Purification by preparative LC/MS affords 1-(3-(5 (4-(difluoromethoxy)phenyl)pyrimidin-2-ylamino)benzyl)piperidine-4-carboxylic acid E3. 1H NMR (400 MHz, d4-MeOH) δ 8.64 (s, 2H), 7.78 (d, J=8.8 Hz, 2H), 7.56 (d, J=8.8 Hz, 2H), 7.32 (d, J=8.8 Hz, 2H), 7.16 (d, J=8.8 Hz, 2H), 6.78 (t, J=74.0 Hz, 1H), 4.11 (s, 2H), 3.31 (m, 2H), 2.92 (m, 2H), 2.36 (m, 1H), 2.02 (m, 2H), 1.81 (m, 2H). MS (m/z) (M+1)+: 455.2.

Provenance & Evidence