Methylamine → HCID 59441920, compound

Participants

Reaction Conditions

Reaction Steps

A slurry of 5-chloro-8-fluoro-3-[(4-methylphenyl)sulfonyl]pyrrolo[2′,3′:4,5]pyrimido[6,1-b]quinazolin-7(3H)-one hydrogen chloride (400 mg, 0.835 mmol) and N1-[3-amino-4-(methyloxy)phenyl]-N2,N2-dimethylglycinamide hydrogen chloride (217 mg, 0.835 mmol) in THF (15 mL) in 2,2,2-trifluoroethanol was stirred at rt. After 3 days LCMS indicated incomplete reaction, therefore more N1-[3-amino-4-(methyloxy)phenyl]-N2,N2-dimethylglycinamide hydrogen chloride (115 mg, 0.24 mmol) was added and the reaction mixture was heated at 80° C. for 4 h. After allowing to cool to rt the reaction mixture was treated with a MeNH2 solution (2M in THF, 20 mL). The reaction mixture was stirred at it for 20 h, then concentrated onto Celite and purified by silica gel chromatography using 1-10% MeOH (containing 0.2% NH3)/CH2Cl2 to obtain 2-({2-{[5-[(N,N-dimethylglycyl)amino]-2-(methyloxy)phenyl]amino}-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)-6-fluoro-N-methylbenzamide as a yellow solid (487 mg, 88%). 1H NMR (400 MHz, DMSO-d6) δ ppm 2.25 (s, 6H), 2.31 (s, 3H), 2.68 (d, J=4.58 Hz, 3H), 3.04 (s, 2H), 3.83 (s, 3H), 6.67 (d, J=4.03 Hz, 1H), 6.96-7.09 (m, 2H), 7.34 (d, J=8.42 Hz, 2H), 7.37-7.45 (m, 2H), 7.53 (dd, J=8.79, 2.56 Hz, 1H), 7.83 (d, J=8.24 Hz, 1H), 7.88-8.00 (m, 3H), 8.39 (br s, 1H), 8.44-8.54 (m, 1H), 9.50 (s, 1H), 10.09 (s, 1H); ESIMS (M+H)+=661.

Provenance & Evidence