反应详情

72 mg of (S)-(+)-5-oxo-tetrahydrofuran-2-carboxylic acid are dissolved in 2.5 ml of N,N-dimethylformamide, combined with 183 mg of (benzotriazol-1-yl)-N,N,N′,N′-tetramethyl-uronium-tetrafluoroborate and stirred for 30 minutes at ambient temperature. This solution is then added to a mixture of 250 mg of 4-[(3-chloro-4-fluorophenyl)amino]-6-cyclopentylmethoxy-7-[2-(piperazin-1-yl)-ethoxy]-quinazoline and 110 μl of triethylamine in 2.5 ml of N,N-dimethylformamide. The reaction mixture is stirred for five hours at ambient temperature. For working up the mixture is poured onto 50 ml of water. A white precipitate is formed, which is suction filtered and washed with water. The crude product is purified by chromatography over an Alox column (activity stage III) with methylene chloride/methanol (98:2) as eluant. The desired product is obtained as a light-coloured solid.

1. stirringThe reaction mixture is stirred for five hours at ambient temperature
2. customA white precipitate is formed
3. filtrationfiltered
4. washwashed with water
5. customThe crude product is purified by chromatography over an Alox column (activity stage III) with methylene chloride/methanol (98:2) as eluant