Sodium Hydroxide → HCID 178486489, compound

Participants

Reaction Steps

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 methyl-1-propanamine (0.22 mL, 2.22 mmol). The resulting mixture was let stir at rt for 6 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-(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 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-(2-methylpropyl)benzamide (50 mg, 0.084 mmol) as a beige solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 0.90 (d, J=6.69 Hz, 6 H) 1.84 (dt, J=13.40, 6.72 Hz, 1 H), 2.24 (s, 6 H), 3.07-3.20 (m, 6 H), 3.76 (s, 3H), 4.16 (t, J=8.34 Hz, 2 H), 6.21 (dd, J=3.21, 1.65 Hz, 1 H), 6.79-6.93 (m, 1 H), 6.93-7.01 (m, 2 H), 7.79 (s, 1 H), 8.39-8.47 (m, 1 H), 8.50 (s, 1 H), 8.63-8.74 (m, 1 H), 10.32 (s, 1 H), 11.32 (br. s., 1 H). (ESIMS (M+H)+=593)

Provenance & Evidence