反应详情

温度

25 °C

A mixture of 4-((1-((4-chlorophenyl)(phenyl)methyl)azetidin-3-yl)-methoxy)-5-cyclopropyl-2-fluorobenzoic acid (50 mg, 0.11 mmol), methanesulfonamide (15 mg, 0.16 mmol), EDCI (31 mg, 0.16 mmol) and DMAP (20 mg, 0.16 mmol) in DCM (20 mL) was stirred at 25° C. for 16 h. The reaction mixture was diluted with EtOAc (100 mL), washed with HCl (2.0 M, 20 mL) and brine (50×2 mL), dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified by reverse phase Combiflash (35%-38% MeCN in 0.5% NH4HCO3) to give the target product (11.0 mg, 19%) as an off-white solid. LCMS (ESI) Method A: RT=5.83 min, m/z: 543.5 [M+H]+. 1H-NMR (500 MHz, MeOH-d4): δ 7.31-7.29 (m, 4H), 7.23-7.19 (m, 5H), 7.14-7.11 (m, 1H), 6.69-6.66 (m, 1H), 4.51 (s, 1H), 4.08 (d, J=6.5 Hz, 2H), 3.39-3.34 (m, 2H), 3.32-3.13 (m, 5H), 2.94-2.90 (m, 1H), 1.99-1.96 (m, 1H), 0.84-0.80 (m, 2H), 0.58-0.54 (m, 2H).

1. washwashed with HCl (2.0 M, 20 mL) and brine (50×2 mL)
2. dry with materialdried over anhydrous sodium sulfate
3. filtrationfiltered
4. concentrationconcentrated
5. customThe residue was purified by reverse phase Combiflash (35%-38% MeCN in 0.5% NH4HCO3)