Sodium Chloride → HCID 178486479, compound

Participants

Reaction Steps

A yellow slurry of 5-chloro-1,8-difluoro-3-[(4-methylphenyl)sulfonyl]pyrrolo[2′,3′:4,5]pyrimido[6,1-b]quinazolin-7(3H)-one hydrogen chloride (578 mg, 1.162 mmol) and 1-[(dimethylamino)acetyl]-5-(methyloxy)-2,3-dihydro-1H-indol-6-amine (290 mg, 1.162 mmol) in THF (110 mL) was stirred at rt for 18 h. 80 mL of the resulting mixture was treated with a 27% aqueous NH4OH solution (100 mL). The reaction mixture was stirred at rt for 4 h. EtOAc (200 mL) and a saturated NaCl solution (50 mL) were added. The organic layer was washed with a saturated NaCl solution (2×100 mL), dried (Na2SO4) and concentrated. The residue was triturated with CH2Cl2 and Et2O. The crude intermediate was taken up into dioxane (10 mL) and treated with a 1N aqueous KOH solution (3 mL, 3.00 mmol). The reaction mixture was heated at 80° C. for 1 h. EtOAc (100 mL) and a saturated NaHCO3 solution (50 mL) were added. 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 obtain 2-[(2-{[1-(N,N-dimethylglycyl)-5-(methyloxy)-2,3-dihydro-1H-indol-6-yl]amino}-5-fluoro-1H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]-6-fluorobenzamide as a pale yellow solid (80 mg). 1H NMR (400 MHz, DMSO-d6) δ ppm 2.25 (s, 6H), 3.06-3.25 (m, 4H), 3.75 (s, 3H), 4.18 (t, J=8.33 Hz, 2H), 6.75-6.94 (m, 2H), 6.98 (s, 1H), 7.18-7.34 (m, 1H), 7.84 (s, 1H), 8.05 (s, 1H), 8.14 (s, 1H), 8.45 (s, 1H), 8.60 (d, J=8.42 Hz, 1H), 10.26 (s, 1H), 11.02 (s, 1H); ESIMS (M+H)+=537.27.

Provenance & Evidence