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 propylamine (0.125 mL, 1.52 mmol). The resulting mixture was let stir at rt for 3 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. The residue was attempted to be purified via chromatography on SiO2 and afforded a 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)-6-fluoro-N-propylbenzamide. 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 solution of 2M NaOH, 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-propylbenzamide (68 mg, 0.121 mmol) as a beige solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 0.86 (t, J=7.38 Hz, 3 H), 1.44-1.57 (m, 2H), 2.26 (s, 6 H), 3.06-3.28 (m, 6 H), 3.18 (s, 2 H), 3.77 (s, 3 H), 4.18 (t, J=8.34 Hz, 2 H), 6.25 (dd, J=3.25, 1.79 Hz, 1 H), 6.84-7.00 (m, 3 H), 7.25-7.38 (m, 1 H), 7.57 (s, 1 H), 8.32 (d, J=8.25 Hz, 1 H), 8.55-8.67 (m, 2 H), 9.86 (s, 1 H), 11.26 (s, 1 H). (ESIMS (M+H)+=561)

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 be purified via chromatography on SiO2
5. customafforded a solid
6. customtransferred to a 20 ml microwave vessel
7. customreaction
8. temperatureheated in microwave at 120° C. for 8 minutes
9. customResulting brown solution
10. washwashed with a solution of 2M NaOH
11. dry with materialOrganics were dried over sodium sulfate and solvents
12. customremoved under reduced pressure
13. customto afford a brown solid which
14. customwas purified via chromatography on SiO2