反应详情

Hydrazine monohydrate (32 μL, 0.65 mmol) was added in one portion to a stirred solution of ethyl cis-4-(4-{[methoxy(oxo)acetyl]amino}phenoxy)cyclohexanecarboxylate (Intermediate 108) (188 mg, 0.54 mmol) in EtOH (3 mL) and the reaction mixture was stirred at room temperature for 10 mins. EtOH (40 mL) and hydrazine monohydrate (9.0 μL, 0.18 mmol) were added and the reaction mixture was stirred for a further 20 mins. Diethylether (50 mL) was added and the mixture was filtered to leave a solid. The filtrate was concentrated in vacuo to leave a gum. The solid and the gum were combined to give the crude hydrazide that was used with no further purification; MS m/e (M−H)− 348. A solution of 2,4,5-trifluorophenyl isothiocyanate (103 mg, 0.54 mmol) in DMA (1 mL) was added in one portion to a stirred solution of the crude hydrazide (189 mg, 0.54 mmol) in DMA (4 mL) and the reaction mixture was stirred at room temperature for 1 h. EDCI (125 mg, 0.65 mmol) was added in one portion and the reaction mixture was heated to 60° C. for 2 mins and then stirred at room temperature for 60 h. The reaction mixture was concentrated in vacuo to leave an oil. Hot water was added and the residue was stirred for 5 min to give a precipitate, which was filtered to give the title compound as a light brown solid (221 mg, 81%); 1H NMR δ 1.20 (3H, t), 1.65-1.71 (4H, m), 1.76-1.85 (4H, m), 2.52 (1H, m), 4.09 (2H, q), 4.51 (1H, s), 6.96 (2H, d), 7.67-7.74 (3H, m), 8.15-8.18 (1H, m), 10.95 (1H, s), 11.05 (1H, s); MS m/e (M−H)− 503.

1. stirringthe reaction mixture was stirred for a further 20 mins
2. filtrationthe mixture was filtered
3. customto leave a solid
4. concentrationThe filtrate was concentrated in vacuo
5. customto leave a gum
6. customto give the crude hydrazide that
7. customwas used with no further purification
8. stirringthe reaction mixture was stirred at room temperature for 1 h
9. temperaturethe reaction mixture was heated to 60° C. for 2 mins
10. stirringstirred at room temperature for 60 h
11. concentrationThe reaction mixture was concentrated in vacuo
12. customto leave an oil
13. stirringthe residue was stirred for 5 min
14. customto give a precipitate, which
15. filtrationwas filtered