Tetrahydrofuran → 4-{[6-(2,6-dichlorophenyl)-8-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl]amino}-1-[(1-methyl-4-nitro-1H-imidazol-5-yl)methyl]pyridinium bromide

Participants

Reaction Steps

To a stirred solution of 6-(2,6-dichlorophenyl)-8-methyl-2-(4-pyridinylamino)pyrido[2,3-d]pyrimidin-7(8H)-one (PD166285 analogue A; Klutchko et al, J Med Chem, 1998, 41(17), 3276-3292) (200 mg, 0.50 mmol) in dry NMP (3 mL)/THF (200 mL) was added 5-(bromomethyl)-1-methyl-4-nitro-1H-imidazole (105) (133 mg, 0.60 mmol). The resulting solution was then stirred at room temperature for 25 days before THF was removed. The resulting solution was partitioned between EtOAc/water. The aqueous portion was subjected to freeze drying and the resulting gum was triturated with Et2O/EtOAc/CH2Cl2 to give 4-{[6-(2,6-dichlorophenyl)-8-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl]amino}-1-[(1-methyl-4-nitro-1H-imidazol-5-yl)methyl]pyridinium bromide (142) (200 mg, 65%) as a pale yellow powder, m.p. 252° C. (dec). 1H NMR [(CD3)2SO] δ 11.83 (bs, 1H), 9.08 (s, 1H), 8.68 (d, J=7.0 Hz, 2H), 8.21 (bs, 2H), 8.09 (s, 1H), 8.05 (s, 1H), 7.61 (dd, J=8.1, 0.6 Hz, 2H), 7.5 (dd, J=8.9, 7.4 Hz, 1H), 6.00 (s, 2H), 3.84 (s, 3H), 3.73 (s, 3H). Analysis found: C, 44.33; H, 3.42; N, 17.00. C24H19BrCl2N8O3.2H2O requires: C, 44.06; H, 3.54; N, 17.13.

Provenance & Evidence