反应详情

To a solution of 5-{[1-(N,N-dimethylglycyl)-5-(methyloxy)-2,3-dihydro-1H-indol-6-yl]amino}-8,10-difluoro-3-[(4-methylphenyl)sulfonyl]pyrrolo[2′,3′:4,5]pyrimido[6,1-b]quinazolin-7(3H)-one (300 mg, 0.445 mmol) in THF (5 mL) was added propylamine (0.183 mL, 2.22 mmol). The resulting mixture was let stir at rt for 5 h at which time it 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 yellow solid, containing 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)-4,6-difluoro-N-propylbenzamide. This crude material was dissolved in 1,4-dioxane (5 mL) and transferred to a 20 ml microwave vessel. A solution of 2 M 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 yellow 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]-4,6-difluoro-N-propylbenzamide (54 mg, 0.093 mmol) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 0.85 (t, J=7.37 Hz, 3 H) 1.41-1.56 (m, 2 H) 2.19 (s, 6 H) 3.02-3.15 (m, 4 H) 3.19-3.25 (m, 2 H) 3.72 (s, 3H) 4.11 (t, J=8.29 Hz, 2 H) 6.17 (d, J=1.28 Hz, 1 H) 6.76-6.87 (m, 1 H) 6.88-6.97 (m, 2 H) 7.74 (s, 1 H) 8.34-8.43 (m, 1 H) 8.45 (s, 1 H) 8.61 (br. s., 1 H) 10.40 (s, 1 H) 11.28 (br. s., 1 H). (ESIMS (M+H)+=579)

1. washwashed with a saturated sodium bicarbonate solution, water
2. dry with materialOrganics were dried over sodium sulfate and solvents
3. customremoved under reduced pressure
4. customto afford a yellow solid
5. customtransferred to a 20 ml microwave vessel
6. customreaction
7. temperatureheated in microwave at 120° C. for 8 minutes
8. customResulting brown solution
9. washwashed with a saturated sodium bicarbonate solution, water
10. dry with materialOrganics were dried over sodium sulfate and solvents
11. customremoved under reduced pressure
12. customto afford a yellow solid which
13. customwas purified via chromatography on SiO2