تفاعل #43698
ord-9101945dc28846d1a5206ab199cd6eac
معادلة التفاعل
المتفاعلات
الكواشف
ظروف التفاعل
المعالجة
- 1workup.ADDITIONAfter addition
- 2درجة الحرارةThe reaction was cooled to 0° C.
- 3درجة الحرارةThe reaction was cooled to −10° C.
- 4أخرىthe reaction
- 5درجة الحرارةto warm to RT
- 6غسيلAfter 1 hour the reaction was washed with aqueous HCl (1N, 10 ml)
- 7غسيلby washing with aqueous NaHCO3 solution (saturated, 10 ml)
- 8تجفيفThe DCM layer was dried over MgSO4
- 9ترشيحfiltered
- 10أخرىthe solvent removed in vacuo
- 11أخرىto yield an off white solid
- 12أخرىThe solid was purified
الإجراء التجريبي
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).