Phosphorus oxybromide → HCID 56848759, compound

Participants

Reaction Conditions

Reaction Steps

To 8-chloro-2-(difluoro(5-fluoropyrimidin-2-yl)methyl)quinazolin-4-ol (200 mg, 0.61 mmol) were added phosphoryl tribromide (1.2 g) and toluene (2 mL) followed by DIEA (0.214 mL, 1.22 mmol). The mixture was heated at 105° C. for 45 min. The mixture was allowed to cool and was partitioned between EtOAc and saturated aq sodium bicarbonate. The organic layer was dried over sodium sulfate and concentrated under reduced pressure. To the crude residue was added a solution of 5-methyl-1H-pyrazol-3-amine (137 mg, 1.41 mmol) in DMF (4 mL) and the mixture was stirred at rt for 45 min. The crude mixture was purified by preparative HPLC (Varian diphenyl reverse phase column, eluting with a gradient of solvent B=0.05% HOAc/ACN and solvent A=0.05% HOAc/H2O) to afford 8-chloro-2-(difluoro(5-fluoropyrimidin-2-yl)methyl)-N-(5-methyl-1H-pyrazol-3-yl)quinazolin-4-amine (75 mg, 30%). 1H NMR (300 MHz, DMSO-d6) δ ppm 2.18 (s, 3H) 5.91 (s, 1H) 7.63 (t, J=8.01 Hz, 1H) 8.07 (d, J=7.54 Hz, 1H) 8.67 (d, J=8.29 Hz, 1H) 9.14 (s, 2H) 10.91 (br s, 1H) 12.24 (br s, 1H); LC-MS (ESI) m/z 406 (M+H)+.

Provenance & Evidence