反应详情

To a solution of 5-chloro-1,3-phenylenediamine (2.00 g) in acetic acid (20 mL) was added 2,5-dimethoxytetrahydrofuran (1.8 mL). After 4 hours at reflux, the reaction mixture was concentrated. The residue was suspended in satd. NaHCO3 and EtOAc. The reaction mixture was filtered and the organic layer was collected, washed with satd. NaHCO3 and brine, dried (Na2SO4), filtered and concentrated. Purification of the residue by chromatography (silica gel: EtOAc/hexane: 1/4) afforded 0.54 g of 3-chloro-5-(1-pyrrolyl)aniline. MS (m/z) 193 (MH+). (2) To a solution of the compound obtained above (0.35 g) in CH2Cl2 (15 mL) was added a solution of trichloroacetyl chloride (0.17 g) dissolved in CH2Cl2 (2 mL). After 45 minutes at room temperature, 2-(4-cyanobenzyl)proline methyl ester (0.38 g) (prepared in a similar fashion to Example 1 (1) and (2)) dissolved in CH2Cl2 (10 mL) and triethylamine (2 mL) were added. After stirring overnight, the mixture was concentrated. The residue was dissolved in EtOAc, washed with satd. NaHCO3 and brine, dried (Na2SO4), filtered and concentrated. Purification by chromatography (silica gel: EtOAc/hexane: 1/4, Chromatotron) afforded 0.51 g of N-[[3-chloro-5-(1-pyrrolyl)phenyl]carbamoyl]-2-(4-bromobenzyl)proline methyl. MS (m/z) 463 (MH+). (3) The titled compound was prepared from the above compound in a fashion similar to Example 1 (4): MS (m/z) 431 (MH+). mp 266.5° C.

1. temperatureAfter 4 hours at reflux
2. concentrationthe reaction mixture was concentrated
3. filtrationThe reaction mixture was filtered
4. customthe organic layer was collected
5. washwashed with satd
6. dry with materialNaHCO3 and brine, dried (Na2SO4)
7. filtrationfiltered
8. concentrationconcentrated
9. customPurification of the residue by chromatography (silica gel: EtOAc/hexane: 1/4)