Реакция #43698

Уравнение реакции

3,5 dichloro-isonicotinoylchloride

Methyl-(2S)-2-[(tert-butoxycarbonyl)amino]-3-[2-(2,6-dichlorophenyl)-6-quinolinyl]propanoate

TFA

→

title compound

Выход 75.0%

methyl-(2S)-2-[(3,5-dichloroisonicotinoyl)amino]-3-[2-(2,6-dichlorophenyl)-6-quinolinyl]propanoate

Выход 75.0%

Растворители

DCM

DCM

DCM

Условия реакции

Обработка

1. 1
   workup.ADDITIONAfter addition
2. 2
   ТемператураThe reaction was cooled to 0° C.
3. 3
   ТемператураThe reaction was cooled to −10° C.
4. 4
   Другоеthe reaction
5. 5
   Температураto warm to RT
6. 6
   ПромывкаAfter 1 hour the reaction was washed with aqueous HCl (1N, 10 ml)
7. 7
   Промывкаby washing with aqueous NaHCO3 solution (saturated, 10 ml)
8. 8
   СушкаThe DCM layer was dried over MgSO4
9. 9
   Фильтрацияfiltered
10. 10
    Другоеthe solvent removed in vacuo
11. 11
    Другоеto yield an off white solid
12. 12
    ДругоеThe solid was purified

Методика

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).

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