(E)-N-(4-(3-bromophenylamino)quinazolin-6-yl)-4-morpholinobut-2-enamide → 4-((2E)-4-{[4-(3-bromoanilino)-6-quinazolinyl]amino}-4-oxo-2-butenyl)-4-[(1-methyl-4-nitro-1H-imidazol-5-yl)methyl]morpholin-4-ium formate

Participants

Reaction Steps

Reaction of (E)-N-(4-(3-bromophenylamino)quinazolin-6-yl)-4-morpholinobut-2-enamide (13) (1.0 g, 2.14 mmol) in NMP (4 mL) with 5-(bromomethyl)-1-methyl-4-nitro-1H-imidazole (105) (313 mg, 1.42 mmol) for 3.5 days according to general procedure D, followed by preparative HPLC using MeOH/formic acid/water as mobile phase gave 4-((2E)-4-{[4-(3-bromoanilino)-6-quinazolinyl]amino}-4-oxo-2-butenyl)-4-[(1-methyl-4-nitro-1H-imidazol-5-yl)methyl]morpholin-4-ium formate (24) (110 mg, 12%), m.p. 125-129° C. 1H NMR [(CD3)2SO] δ 11.69 (s, 1H), 10.17 (s, 1H), 9.28 (s, 1H), 8.65 (br, 1H), 8.61 (s, 1H), 8.44-8.40 (m, 2H), 8.14 (s, 1H), 8.07 (d, J=8.1 Hz, 1H), 7.34 (t, J=8.1 Hz, 1H), 7.27 (d, J=8.5 Hz, 1H), 7.17-7.10 (m, 2H), 6.82 (d, J=14.6 Hz, 1H), 5.12 (br s, 2H), 4.81 (br s, 2H), 4.16 (t, J=12.0 Hz, 2H), 3.91 (m, 2H), 3.88 (s, 3H), 3.70-3.60 (m, 2H), 3.46 (t, J=12.0 Hz, 2H). FIRMS (FAB+) found: 607.14189, 609.14034 (M-HCOO), calcd. for C27H2879/81BrN8O4+: 607.14169, 609.13964.

Provenance & Evidence