Diisopropylamine → 6-methoxy-N-[7-(3-methoxyprop-1-ynyl)-1,3-benzodioxol-4-yl]-7-(3-morpholin-4-ylpropoxy)quinazolin-4-amine

Participants

Reaction Steps

Bis(Triphenyl-phosphine)palladium(II) chloride (94 mg), copper iodide (19 mg) and diisopropylamine (68 mg) were added to a stirred solution of N-(7-iodo-1,3-benzodioxol-4-yl)-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazolin-4-amine (200 mg) and methyl propargyl ether (47 mg) in ethyl acetate (5 mls) at −20° C. The reaction was allowed to warm to ambient temperature and stirred over 16 hours. The reaction mixture was partitioned between ethyl acetate and saturated NaHCO3. The organic layer was washed with water and saturated brine and dried over magnesium sulfate. The product was purified by column chromatography on silica using a gradient of 0-10% methanol/methylene chloride as eluent. The resultant yellow gum was dissolved in minimal methylene chloride, diluted with diethyl ether and precipitated as an HCl salt by the addition of 1.0 M ethereal hydrogen chloride. The resultant solid was centrifuged and washed with diethyl ether (3 times) and dried to give the title compound as a yellow solid (55 mg); NMR Spectrum: DMSOd6) 2.29-2.36 (m, 2H); 3.03-3.14 (m, 2H); 3.24 -3.31 (m, 2H), 3.32 (s, 3H), 3.43-3.54 (m, 2H), 3.76-3.86 (m, 2H), 3.94 -4.00 (m, 5H), 4.31 (t, 2H), 4.35 (s, 2H), 6.13 (s, 2H), 6.98 (d, 1H), 7.02 (d, 1H), 7.40 (s, 1H), 8.27 (s, 1H), 8.80 (s, 1H); Mass Spectrum: M+H+ 507.11

Provenance & Evidence