반응 #43698
ord-9101945dc28846d1a5206ab199cd6eac
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후처리
- 1workup.ADDITIONAfter addition
- 2온도The reaction was cooled to 0° C.
- 3온도The reaction was cooled to −10° C.
- 4기타the reaction
- 5온도to warm to RT
- 6세척After 1 hour the reaction was washed with aqueous HCl (1N, 10 ml)
- 7세척by washing with aqueous NaHCO3 solution (saturated, 10 ml)
- 8건조The DCM layer was dried over MgSO4
- 9여과filtered
- 10기타the solvent removed in vacuo
- 11기타to yield an off white solid
- 12기타The solid was purified
실험 절차
Methyl-(2S)-2-[(tert-butoxycarbonyl)amino]-3-[2-(2,6-dichlorophenyl)-6-quinolinyl]propanoate (compound No 26, international patent application WO 03/093237) (500 mg, 1.05 mmol) was dissolved in DCM (5 ml) and a solution of TFA (0.8 ml, 10.5 mmol) in DCM (2 ml) was added drop wise over 10 minutes. After addition was complete the reaction was stirred at RT over night. The reaction was cooled to 0° C. and TEA (2.1 ml, 15.8 mmol) in DCM (2 ml) was added drop wise over 10 minutes. The reaction was cooled to −10° C. and 3,5 dichloro-isonicotinoylchloride (Bioorg. Med. Chem. Lett. 2002, 12, 1591-1594), (663 mg, 3.0 mmol) was added drop wise over 10 minutes, before allowing the reaction to warm to RT. After 1 hour the reaction was washed with aqueous HCl (1N, 10 ml), followed by washing with aqueous NaHCO3 solution (saturated, 10 ml). The DCM layer was dried over MgSO4, filtered and the solvent removed in vacuo to yield an off white solid. The solid was purified using flash chromatography (eluent EtAc) to yield the title compound as a white powder (432 mg, 75%) LCMS M+1 (552, 550, 548), Retention Time 3.82 min, 1H NMR, 300 Mz, d6-DMSO-9.50 (1H, d), 8.63 (2H, s), 8.42 (1H, d), 7.98 (1H, d), 7.94 (1H, d), 7.78 (1H, dd), 7.65 (2H, d), 7.55 (2H, m), 4.95 (1H, m), 3.74 (3H, s), 3.45 (1H, dd), 3.20 (1H, dd).