反应详情

A mixture of tert-butyl {1-[4-(2-bromo-9H-imidazo[1,2-d]pyrido[2,3-b][1,4]benzodiazepin-3-yl)phenyl]cyclobutyl}carbamate (50 mg, 0.090 mmol), [6-(methoxycarbonyl)pyridin-3-yl]boronic acid (32 mg, 0.18 mmol), bis (di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (6 mg, 0.09 mmol), and 2M Na2CO3 aq. (0.090 mL, 0.18 mmol) in DMF (2.5 mL) was treated with microwave (160° C. for 1 hour). The reaction mixture was added potassium carbonate (30 mg, 0.22 mmol) and iodomethane (0.050 mL, 0.80 mmol) and stirred at r.t for 17 hours. The mixture was diluted with AcOEt, washed with water(×3), brine, dried over Na2SO4, then filtrated through Celite pad. The filtrate was concentrated and the residue was purified by preparative thin-layer chromatography (n-hexane/AcOEt=1:3) to afford the desired product (52 mg, 95%) as a pale yellow solid. 1HNMR (CDCl3) 400 MHz δ: 8.83 (d, J=2.3 Hz, 1H), 8.15 (dd, J=7.4 Hz and 1.7 Hz, 1H), 8.09 (d, J=8.0 Hz, 1H), 8.02 (d, J=4.0 Hz, 1H), 7.41 (d, J=8.0 Hz, 2H), 7.34 (td, J=7.4 Hz and 1.7 Hz, 1H), 7.19-7.17 (m, 3H), 6.96 (d, J=8.0 Hz, 1H), 6.80 (d, J=7.4 Hz, 1H), 6.60 (dd, J=8.0 Hz and 4.6 Hz, 1H), 6.26 (s, 1H), 5.14 (br s, 1H), 3.99 (s, 3H), 2.59-2.53 (m, 2H), 2.51-2.42 (m, 2H), 2.20-2.12 (m, 1H), 1.96-1.88 (m, 1H), 1.40 (br s, 9H). LCMS: 615 [M+H].

1. additionwas treated with microwave (160° C. for 1 hour)
2. washwashed with water(×3), brine
3. dry with materialdried over Na2SO4
4. filtrationfiltrated through Celite pad
5. concentrationThe filtrate was concentrated
6. customthe residue was purified by preparative thin-layer chromatography (n-hexane/AcOEt=1:3)