反应详情

A solution of N1-[3-({8-fluoro-3-[(4-methylphenyl)sulfonyl]-7-oxo-3,7-dihydropyrrolo[2′,3′:4,5]pyrimido[6,1-b]quinazolin-5-yl}amino)-4-(methyloxy)phenyl]-N1,N2,N2-trimethylglycinamide (0.800 g, 1.243 mmol) in tetrahydrofuran (75 ml) was treated with 2.0M methyl amine (3.11 ml, 6.21 mmol) and maintained at room temperature overnight. The reaction was taken to a residue under reduced pressure, dissolved in 1,4-dioxane (8 ml), and added to a microwave vial along with 2.0N NaOH (aq) (8 ml). The mixture was maintained under microwave heating at 120° C. for 12 minutes, cooled, and poured into saturated sodium bicarbonate and ethyl acetate. The organic layer was separated, dried over sodium sulfate, filtered, stripped onto celite, and purified by column chromatography to afford 2-[(2-{[5-[(N,N-dimethylglycyl)(methyl)amino]-2-(methyloxy)phenyl]amino}-1H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]-6-fluoro-N-methylbenzamide (0.140 g, 0.269 mmol, 21.64% yield) as a pale yellow solid. 1H NMR (400 MHz, DMSO-d6) 6 ppm 11.47 (br. s., 1 H), 10.05 (s, 1 H), 8.54 (d, J=3.8 Hz, 1 H), 8.44 (br. s., 1 H), 8.14 (d, J=8.2 Hz, 7.59 (s, 1 H), 7.36-7.50 (m, 1 H), 6.93-7.06 (m, 3 H), 6.84 (br. s., 1 H), 6.35 (br.s., 1 H), 3.91 (s, 3 H), 3.11 (s, 3 H), 2.86 (s, 2 H), 2.77 (d, J=4.4 Hz, 3 H), 2.11 (s, 6 H). ESIMS (M+H)+=521.

1. temperatureThe mixture was maintained under microwave
2. temperatureheating at 120° C. for 12 minutes
3. temperaturecooled
4. customThe organic layer was separated
5. dry with materialdried over sodium sulfate
6. filtrationfiltered
7. custompurified by column chromatography