p-Toluenesulfonic acid → 5,7-Difluoro-2-(6-(4-isopropylpiperazin-1-yl)pyridin-2-yl)quinazolin-4(3H)-one

Participants

Reaction Conditions

Reaction Steps

A mixture of 2-amino-4,6-difluorobenzamide (7, 330 mg, 1.70 mmol), 6-(4-isopropylpiperazin-1-yl)picolinaldehyde (8, Scheme 6, 330 mg, 1.42 mmol), p-toluenesulfonic acid (590 mg, 3.12 mmol), NaHSO3 (370 mg, 3.55 mmol) and DMA (15 mL) was heated for 24 h at 110° C. under nitrogen. The mixture was partitioned between water (25 mL) and CH2Cl2 (25 mL) and shaken vigorously. The layers were separated and the organic phase was dried over sodium sulfate and filtered. The solvent was removed under reduced pressure and the residue was purified by silica gel chromatography eluting with 0-5% MeOH in CH2Cl2 to provide the title compound (112 mg, 20%): 1H NMR (500 MHz, CDCl3) δ 10.59 (s, 1H), 7.85 (d, J=7.3 Hz, 1H), 7.67 (dd, J=7.3, 8.5 Hz, 1H), 7.30-7.26 (m, 1H), 6.93-6.89 (m, 1H), 6.86 (d, J=8.5 Hz, 1H), 3.69-3.60 (m, 4H), 2.82-2.73 (m, 1H), 2.71-2.66 (m, 4H), 1.12 (s, 3H), 1.11 (s, 3H).

Provenance & Evidence