反应详情

A mixture of 6-[(4-tert-butylphenyl)sulfonyl]-2-(trifluoromethyl)-6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepine-8-carboxylic acid (intermediate 58, 60 mg, 0.119 mmol), acetamide oxime (10 mg, 0.141 mmol), DIPEA (18 mg, 0.141 mmol), HOBt (19 mg, 0.14 mmol), DIC (23 mg, 0.18 mmol) in DCM (0.4 mL) and DMF (0.1 mL) was stirred at rt for 3 h. The reaction was quenched with water and the product was extracted with EtOAc. The combined extracts were washed with 5% NaHCO3, brine, dried (MgSO4) and concentrated. The residue was dissolved in NMP and was heated in a microwave reactor at 120° C. for 1 h. The reaction was quenched with water and the product was extracted with EtOAc. The extracts were washed with water and brine, dried (MgSO4) and concentrated. Flash column purification of the residue on SiO2 afforded the title compound. LC/MS: m/e 544.1 (M+H)+. 1H NMR (500 MHz, CDCl3): δ 8.38 (1H, d, J=1.6 Hz), 8.00 (1H, dd, J=8.4, 1.8 Hz), 7.63 (1H, d, J=7.4 Hz), 7.16 (1H, d, J=7.4 Hz), 7.13 (1H, d, J=8.4 Hz), 7.05 (1H, br s), 6.97 (2H, J=8.5 Hz), 6.90 (1H, d, J=8.4 Hz), 4.65-4.95 (2H, br), 2.51 (3H, s), 1.26 (9H, s).

1. customThe reaction was quenched with water
2. extractionthe product was extracted with EtOAc
3. washThe combined extracts were washed with 5% NaHCO3, brine
4. dry with materialdried (MgSO4)
5. concentrationconcentrated
6. dissolutionThe residue was dissolved in NMP
7. temperaturewas heated in a microwave reactor at 120° C. for 1 h
8. customThe reaction was quenched with water
9. extractionthe product was extracted with EtOAc
10. washThe extracts were washed with water and brine
11. dry with materialdried (MgSO4)
12. concentrationconcentrated
13. customFlash column purification of the residue on SiO2