4-Chloro-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazoline → N-[5-chloro-7-(3-methoxyprop-1-ynyl)-1,3-benzodioxol-4-yl]-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazolin-4-amine

Participants

Reaction Conditions

Reaction Steps

Sodium hexamethyldisilazane (1M solution in THF; 1.0 ml) was added to a mixture of 4-chloro-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazoline (0.16 g) and 5-chloro-7-(3-methoxyprop-1-ynyl)-1,3-benzodioxol-4-amine (0.12 g) in DMA (5 ml) that was cooled to 0° C. The resultant mixture was stirred and allowed to warm to ambient temperature for 2 hours. The reaction mixture was reduced in vacuo and partitioned between ethylacetate and water. The organic layers were washed with water and brine and the product was purified 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 1.0M ethereal HCl. The resultant solid was centrifuged and washed with diethyl ether (3 times) and dried to give the title compound as a yellow solid (185 mg); NMR Spectrum: (DMSOd6+CD3CO2D at 100° C.) 2.33-2.40 (m, 2H), 3.30-3.40 (m, 9H), 3.93-3.98 (m, 4H), 4.03 (s, 3H), 4.38-4.41 (m, 4H), 6.19 (s, 2H), 7.15 (s, 1H), 7.41 (s, 1H), 8.16 (s, 1H), 8.66 (s, 1H); Mass Spectrum: M+H+ 541.5.

Provenance & Evidence