Phosphorus oxychloride → Methyl 4-{[4-chloro-3-(trifluoromethyl)benzyl]amino}-6-nitroquinazoline-8-carboxylate

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Reaction Conditions

Reaction Steps

To a solution of methyl 6-nitro-4-oxo-3,4-dihydroquinazoline-8-carboxylate (250 mg, 1.0 mmol) in 5 mL of anhydrous DCE, POCl3 (110 μL, 1.2 mmol, 1.2 equiv.) was added followed by DIPEA (870 μL, 5.0 mmol, 5.0 equiv.). The resulting mixture was stirred at 90° C. for 1 h. After cooling down to rt, 4-chloro-3-(trifluoromethyl)benzylamine (230 mg, 1.1 mmol, 1.1 equiv.) was added. The reaction mixture was stirred at 80° C. for 3 h. After work-up, the crude was purified by flash chromatography to yield the title compound in 46% yield. 1HNMR (in DMSO): 3.91 (s, 3H), 4.88 (d, J=5.9 Hz, 2H), 7.65-7.71 (m, 2H), 7.91 (s, 1H), 8.64 (s 1H), 8.68 (d, J=2.2 Hz, 1H), 9.49 (d, J=2.4 Hz, 1H), 9.70 (t, J=5.7 Hz, 1H). Mass: M+H+: 441.

Provenance & Evidence