Triphenylphosphine → HCID 22624995, compound

Participants

Reaction Steps

Diethyl azodicarboxylate (295 μl, 1.8 mmol) was added dropwise to a solution of 2-methyl-1-(3-hydroxypropyl)imidazole (131 mg, 0.93 mmol), (EP 0060696 A1), triphenylphosphine (492 mg, 1.8 mmol) and 4-(4-chloro-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (200 mg, 0.62 mmol), (prepared as described for the starting material in Example 24), in methylene chloride (4 ml) and the mixture stirred for 2 hours at ambient temperature. Further 2-methyl-1-(3-hydroxypropyl)imidazole (43 mg, 0.31 mmol), triphenylphosphine (82 mg, 0.31 mmol) and diethyl azodicarboxylate (50 μl, 0.31 mmol) were added and the mixture stirred for a further 3 hours. The volatiles were removed by evaporation and the residue was purified by column chromatography eluting with methylene chloride/methanol (93/7). The purified solid was dissolved in methylene chloride and 3M ethereal hydrogen chloride (2 ml) was added. The volatiles were removed by evaporation and the solid residue was suspended in ether, collected by filtration, washed with ether and dried under vacuum to give 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(3-(2-methylimidazol-1-yl)propoxy)quinazoline hydrochloride (104 mg, 32%). 1H NMR Spectrum: (DMSOd6; CF3COOD) 2.4(t, 2H); 2.60(s, 3H); 4.0(s, 3H); 4.3-4.4(m, 4H); 7.41(s, 1H); 7.46(dd, 1H); 7.58(s, 1H); 7.62(t, 1H); 7.67(dd, 1H); 7.70(s, 1H); 8.21(s, 1H); 8.88(s, 1H) MS-ESI: 442 [MH]+

Provenance & Evidence