反应详情

A solution of ({[3-methoxy-4-(3-o-tolylureido)phenyl]-acetyl}-N-methylamino)-acetic acid [18.4 g, Reference Example 1] and 3-(3,4-dimethoxy-benzylamino)-propionic acid ethyl ester [13.4 g, Reference Example 2(a)] in dimethylformamide (400 ml) was treated with [O-(7-azabenzotriazol-1-yl)-1,1,3,3,-tetramethyluronium hexafluorophosphate] (19.1 g) and diisopropylethylamine (10.5 ml). After stirring at ambient temperature for 20 hours the reaction mixture was evaporated to dryness. The residue was treated with water (800 ml) followed by hydrochloric acid (175 ml 1 M) and the mixture was extracted twice with ethyl acetate (500 ml). The combined organic extracts were washed with hydrochloric acid (500 ml, 1M), then with water (400 ml), then with saturated aqueous sodium bicarbonate solution (500 ml), then dried over magnesium sulphate and then evaporated. The residual oil was subjected to flash chromatography on silica eluting with a mixture of dichloromethane and methanol (49:1, v/v) to give the title compound as a fawn coloured foam (26.4 g), m.p. 97-105° C. [Elemental analysis:- C,63.4; H,6.7; N,8.7% Calculated for C34H42N4O8.0.5H2O:- C,63.3; H,6.8; N,8.8%].

1. customwas evaporated to dryness
2. additionThe residue was treated with water (800 ml)
3. extractionthe mixture was extracted twice with ethyl acetate (500 ml)
4. washThe combined organic extracts were washed with hydrochloric acid (500 ml, 1M)
5. dry with materialwith water (400 ml), then with saturated aqueous sodium bicarbonate solution (500 ml), then dried over magnesium sulphate
6. customevaporated
7. additionThe residual oil was subjected to flash chromatography on silica eluting with a mixture of dichloromethane and methanol (49:1