反应详情

5-(6-Aminopyridin-3-yl)-7-chloro-1-methyl-3-(naphthalen-2-ylmethyl)-1H-benzo[e][1,4]diazepin-2(3H)-one (50 mg, 0.11 mmol) was dissolved in dichloromethane (0.5 mL), and triethylamine (19 μL, 0.14 mmol) was added followed by acetoxyacetyl chloride (13 μL, 0.12 mmol). A slightly exothermic reaction occurred. This mixture as stirred at ambient temperature overnight. Additional triethylamine (46 μL, 0.33 mmol) was added followed by acetoxyacetyl chloride (30 μL, 0.22 mmol) and stirring continued at ambient temperature for 4 days. Concentration in the presence of silica, then column chromatography eluting with a step gradient of 20-80% ethyl acetate in hexanes in 5% increments every 3 minutes provided 2-(5-(7-chloro-1-methyl-3-(naphthalen-2-ylmethyl)-2-oxo-2,3-dihydro-1H-benzo[e][1,4]diazepin-5-yl)pyridin-2-ylamino)-2-oxoethyl acetate (45 mg, 73%). 1H NMR (300 MHz, d6-DMSO) δ 2.10 (s, 3H), 3.3 (s, 3H), 3.53 (d, 2H) 3.83 (t, 1H), 4.72 (s, 2H), 7.30 (m, 1H), 7.4-7.5 (m, 3H), 7.60 (m, 2H), 7.65 (m, 1H), 7.77-7.88 (m, 4H), 8.03 (m, 1H), 8.36, (m, 1H), 10.94 (s, 1H); ESI m/z measured 541.1646 [M+H]+. calculated 541.1643.

1. customA slightly exothermic reaction
2. stirringstirring
3. waitcontinued at ambient temperature for 4 days
4. concentrationConcentration in the presence of silica
5. washcolumn chromatography eluting with a step gradient of 20-80% ethyl acetate in hexanes in 5% increments every 3 minutes