Ammonium Hydroxide → HCID 59441804, compound

Participants

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 (600 mg, 1.252 mmol) and (2R)-1-[(dimethylamino)acetyl]-2-methyl-5-(methyloxy)-2,3-dihydro-1H-indol-6-amine (330 mg, 1.252 mmol) in 2,2,2-trifluoroethanol (10 mL) was stirred at rt for 18 h. The resulting bright green slurry was divided into two equal batches. One of the batches was treated with a 27% aqueous NH4OH solution (10 mL). The resulting orange slurry was stirred at rt for 2 days, then was diluted with EtOAc (50 mL) and a saturated NaHCO3 solution (50 mL). The organic layer was washed with a saturated NaCl solution (50 mL), concentrated onto Celite and purified by silica gel chromatography using 1-10% MeOH (containing 0.2% NH3)/CH2Cl2 to afford 2-({2-{[(2R)-1-(N,N-dimethylglycyl)-2-methyl-5-(methyloxy)-2,3-dihydro-1H-indol-6-yl]amino}-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)-6-fluorobenzamide as a yellow solid (249 mg, 58%). 1H NMR (400 MHz, DMSO-d5) δ ppm 1.18-1.32 (m, 3H), 2.27 (br s, 6H), 2.33 (s, 3H), 2.63 (d, J=16.12 Hz, 1H), 3.14 (d, J=14.65 Hz, 1H), 3.27-3.51 (m, 2H), 3.76 (s, 3H), 4.75-4.87 (m, 1H), 6.53 (d, J=4.03 Hz, 1H), 6.94 (t, J=9.34 Hz, 1H), 7.06 (s, 1H), 7.14-7.42 (m, 4H), 7.72-8.04 (m, 4H), 8.07 (d, J=8.24 Hz, 1H), 8.18 (s, 1H), 8.25 (s, 1H), 10.46 (s, 1H). ESIMS (M+H)+=687.26.

Provenance & Evidence