Calcium Carbonate → 2,2-Dimethylpropanoic acid, [6-[[(4-acetylphenyl)-2-propynylamino]methyl]-4-oxo-3(4H)-quinazolinyl]methyl ester

Participants

Reaction Conditions

Reaction Steps

A suspension of 5.79 g (12.5 mmol) of 75% pure 2,2-dimethylpropanoic acid, [6-(bromomethyl)-4-oxo-3(4H)-quinazolinyl]methyl ester (European patent application 204,529), 2.89 g (16.7 mmol) of 1-[4-(2-propynylamino)phenyl]ethanone (see Example A), and 3.34 g (33.4 mmol) of dry calcium carbonate in 100 ml of dimethylacetamide (DMA) is stirred at 80° C. for eighteen hours. The suspension is poured into a water-ice mixture and stirred. The suspension is extracted with ethyl acetate. The ethyl acetate solution is dried (magnesium sulfate) and concentrated to give 10.4 g of a yellow oil. This is dissolved in a minimum amount of dichloromethane and applied to a column of 1 kg of flash silica gel packed in dichloromethane/methanol (100:1). Elution with the same solvent gives 2.83 g (50.8%) of impure product as a yellow gum followed by 2.34 g (42.0% assuming 75% pure bromomethyl compound) of the product as a cream colored foam. This is used as is without characterization in the next reaction.

Provenance & Evidence