Diethyl Pyrocarbonate → 1-[(5-chloro-2-thienyl)sulfonyl-ethyl-amino]-N-[[2-[4-(cyclopropylmethyl)piperazin-1-yl]-6-[4-(trifluoromethyl)phenyl]-4-pyridyl]methyl]cyclopropanecarboxamide

Participants

Reaction Steps

A solution of acid 18 (463 mg, 1.5 mmol) in THF (30 mL) was added with DEPC (0.23 mL, 1.0 mol eq) and the mixture was stirred at room temperature for about 5 minutes. Then [2-[4-(cyclopropylmethyl)piperazin-1-yl]-6-[4-(trifluoromethyl)phenyl]-4-pyridyl]methanamine 27G (560 mg, 1.04 mol eq) and a catalytic amount of TEA were added, then the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, the residue was suspended in EtOAc (40 mL) and washed with water (50 mL) and brine. The separated organic phase was dried over Na2SO4 and evaporated under reduced pressure and the residue was purified by flash chromatography (9:1 EtOAc:methanol) to afford a white solid (220 mg) after crystallization from diethyl ether. Yield=21.5%, 1HNMR (DMSO, 200 MHz) δ 0.40 (m, 2H), 0.65 (bm, 2H), 0.94 (m, 1H), 1.12 (m, 2H), 1.28 (t, 3H), 1.40 (bm, 2H), 3.04 (bm, 4H), 3.39 (bm, 4H), 3.43 (bm, 2H), 3.44 (m, 4H); 4.40 (bm, 4H), 6.87 (s, 1H), 7.30 (m, 2H), 7.60 (d, 1H, J=3.2), 7.82 (d, 2H, J=8.2), 8.25 (bm, 3H). [M+1] 682.98 (C31H35ClF3N5O3S2 requires 682.22).

Provenance & Evidence