反应详情

To an ice cooled solution of piperidine-4-carboxylic acid [2-(2,4-dichlorophenoxy)phenyl]-amide (AMR01038, 80 mg, 0.219 mmol) in dry DCM (6 mL) were added triethylamine (0.3 mL, 2.19 mmol) and methanesulphonyl chloride (0.034 mL, 0.438 mmol). The reaction mixture was stirred at room temperature for 24 h, and quenched with saturated NaHCO3. The resulting solution was extracted with DCM (3×20 mL), and the combined organic layers were washed with water, 1M HCl (3×20 mL) and brine, dried (MgSO4), filtered and evaporated. Flash chromatography on silica gel using DCM to DCM/MeOH 95:5 gradient as eluent gave 1-methanesulfonyl-piperidine-4-carboxylic acid [2-(2,4-dichloro-phenoxy)-phenyl]-amide (47.6 mg, 49%) as an oil. Rf: 0.25 (hexane/EtOAc 4:6). 1H NMR (300 MHz, CDCl3) δ 1.88 (2H, m, CH2), 2.37 (1H, m, CH), 2.72 (3H, s, CH3), 2.78 (2H, m, CH2), 3.71 (2H, td, J=12.5, 3.6 Hz, CH2), 6.67 (1H, dd, J=8.1, 1.3 Hz, ArH), 6.89 (1H, d, J=8.8 Hz, ArH), 6.95 (1H, td, J=8.1, 1.6 Hz, ArH), 7.07 (1H, td, J=8.0, 1.3 Hz, ArH), 7.16 (1H, dd, J=8.8, 2.5 Hz, ArH), 7.43 (1H, d, J=2.5 Hz, ArH), 7.72 (1H, br s, NH) and 8.31 (1H, br d, J=8.1 Hz, ArH). Further purification by flash chromatography on silica gel using hexane/EtOAc 4:6 as eluent gave AMR01051 as a white solid, mp 150-151° C. LC/MS (APCI) tr=4.63 min, m/z 443.37 (M++H, 100), 445.39 (55). HPLC tr=2.52 min (100%)

1. customquenched with saturated NaHCO3
2. extractionThe resulting solution was extracted with DCM (3×20 mL)
3. washthe combined organic layers were washed with water, 1M HCl (3×20 mL) and brine
4. dry with materialdried (MgSO4)
5. filtrationfiltered
6. customevaporated