Dichloromethane → Methyl 3-{[(4-{3-[1-(tert-butoxycarbonyl)-4-piperidinyl]anilino}-4-oxobutyl)amino]carbonyl}-4-(4-fluorophenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydro-5-pyrimidinecarboxylate

Participants

Reaction Steps

A 10-mL RB-flask was charged with 4-{[(6-(4-fluorophenyl)-5-(methoxycarbonyl)-4-methyl-2-oxo-3,6-dihydro-1(2H)-pyrimidinyl)carbonyl]amino}butanoic acid (77.0 mg, 0.189 mmol), tert-butyl-4-[3-(amino)phenyl]-1-piperidinecarboxylate (52.2 mg, 0.189 mmol), 1-[3-(dimethylamino)propyl]-3-ethylcarbodimide hydrochloride (0.567 mmol, 87.8 mg), 4-dimethylaminopyridine (11.5 mg, 0.0945 mmol) in DMF:DCM (0.2:2.0 mL) at room temperature. The reaction mixture was stirred for 12 h and water (10.0 mL) was added to the reaction mixture. The organic layer was separated and the aqueous layer was extracted with CHCl3 (3×10 mL). The combined organic extracts were washed with brine, dried over MgSO4, filtered and concentrated in vacuo. The residue was chromatographed (silica, hexanes:EtOAc 9:1) to afford the desired product (40.9 mg, 33.2%): 1H NMR (400 MHz, CDCl3) δ 8.03 (m, 3H), 7.57 (s, 1H), 7.36-7.28 (m, 3H), 7.27-7.22 (m, 1H), 6.97-6.89 (m, 3H), 6.72 (s, 1H), 3.72 (s, 3H), 3.47-3.37 (m, 2H), 2.42 (s, 3H), 2.37-2.29 (m, 2H), 1.98-1.91 (m, 2H), 1.86-1.75 (m, 2H), 1.72-1.54 (m, 7H), 1.48 (s, 9H); ESMS m/e: 652.2 (M+H)+.

Provenance & Evidence