反应详情

To a solution of 5-{[1-(N,N-dimethylglycyl)-5-(methyloxy)-2,3-dihydro-1H-indol-6-yl]amino}-8-fluoro-3-[(4-methylphenyl)sulfonyl]pyrrolo[2′,3′:4,5]pyrimido[6,1-b]quinazolin-7(3H)-one (200 mg, 0.305 mmol) in THF (5 mL) was added (2-methylpropyl)amine (0.153 mL, 1.52 mmol). The resulting mixture was let stir at rt for 16 h at which time it was diluted with ethyl acetate and washed with a saturated ammonium chloride solution,a saturated sodium bicarbonate solution, water and a saturated brine solution. Organics were dried over sodium sulfate and solvents removed under reduced pressure to afford a brown solid 2-({2-{[1-(N,N-dimethylglycyl)-5-(methyloxy)-2,3-dihydro-1H-indol-6-yl]amino}-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)-6-fluoro-N-(2-methylpropyl)benzamide. This crude material was dissolved in 1,4-dioxane (5 mL) and transferred to a 20 ml microwave vessel. A solution of 2M NaOH (5 ml) was added and reaction heated in microwave at 120° C. for 8 minutes. Resulting brown solution was diluted with ethyl acetate and washed with a saturated sodium bicarbonate solution, water and a saturated brine solution. Organics were dried over sodium sulfate and solvents removed under reduced pressure to afford a brown solid which was purified via chromatography on SiO2 to afford 2-[(2-{[1-(N,N-dimethylglycyl)-5-(methyloxy)-2,3-dihydro-1H-indol-6-yl]amino}-1H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]-6-fluoro-N-(2-methylpropyl)benzamide (106 mg, 0.184 mmol) as a pale yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 0.87 (d, J=6.68 Hz, 6 H), 1.73-1.89 (m, 1 H), 2.26 (s, 6 H), 3.05-3.23 (m, 6 H), 3.77 (s, 3 H), 4.18 (t, J=8.33 Hz, 2 H), 6.24 (br. s., 1 H), 6.83-7.00 (m, 3 H), 7.24-7.38 (m, 1 H), 7.56 (s, 1 H), 8.32 (d, J=8.42 Hz, 1 H), 8.57-8.68 (m, 2 H), 9.77 (s, 1 H), 11.26 (br. s., 1 H). (ESIMS (M+H)+=575)

1. washwashed with a saturated ammonium chloride
2. dry with materialOrganics were dried over sodium sulfate and solvents
3. customremoved under reduced pressure