反应详情

温度

10 °C

A stirred solution of 1-benzoyl-4-(4-{2-[3-methoxy-4-(3-o-tolyl-ureido)-phenyl]-acetylamino}-phenyl)-pyrrolidine-3-carboxylic acid ethyl ester (5 g, Reference Example 7) in ethanol (60 ml), at 23° C., was treated dropwise with sodium hydroxide solution (16 ml, 1N). After stirring for 24 hours the mixture was evaporated (40° C. and 2.7 kPa) and the residue was treated with water (300 ml). The mixture was cooled to 10° C, then treated with hydrochloric acid (25 ml, 1N) and then stood at 23° C. for 20 hours. The resulting white precipitate was filtered, then dried under reduced pressure (40° C. and 2.7 kPa) for 45 minutes and then recrystallised from aqueous ethanol (40 ml) affording the title compound (3.25 g) as a white crystalline powder, m.p. 248° C. TLC: RF=45/78 (on silica eluting with a mixture of dichloromethane and methanol, 90:10). 1H-NMR [500 MHz, (CD3)2SO at 373°K.]: δ 2.29 (s, 3H); 3.26 (m, 1H); 3.50 to 3.65 (m, 2H); 3.61 (s, 2H); 3.76 (m, 1H);3.85 to 4.00 (m, 2H); 3.91 (s, 3H); 6.88 (d, J=8 Hz, 1H); 6.99 (t, J=7.5 Hz, 1H); 7.03 (bs, 1H); 7.14 (t, J=7.5 Hz, 1H); 7.18 (d, J=7.5 Hz, 1H); 7.26 (d, J=8.5 Hz, 2H); 7.45 (m, 3H); 7.55 (m, 4H); 7.70 (d, J=7.5 Hz, 1H); 8.01 (d, J=8 Hz, 1H); 8.10 (bs, 1H); 8.26 (bs, 1H); 9.64 (bs, 1H); 11.50 to 12.30 (b, 1H). MS [FAB (meta-nitrobenzylalcohol)]: 607 [M+H]+.

1. customwas evaporated (40° C. and 2.7 kPa)
2. additionthe residue was treated with water (300 ml)
3. additiontreated with hydrochloric acid (25 ml, 1N)
4. waitstood at 23° C. for 20 hours
5. filtrationThe resulting white precipitate was filtered
6. customdried under reduced pressure (40° C. and 2.7 kPa) for 45 minutes
7. customrecrystallised from aqueous ethanol (40 ml)