反应详情

To a solution of cis-1,2-cyclopropanediamine hydrochloride (J. Med. Chem., vol. 41, pp. 4723-4732 (1998)) (405 mg) and 5-chloroindole-2-carboxylic acid (546 mg) in N,N-dimethylformamide (10 mL) were added 1-hydroxybenzotriazole monohydrate (377 mg), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (642 mg), and diisopropylethylamine (1.95 mL) at room temperature, followed by stirring for 50 hours. The reaction mixture was concentrated under reduced pressure, and thereto were added methylene chloride (50 mL) and saturated aqueous sodium hydrogencarbonate (200 mL). The precipitated colorless solid was filtered off. The filtrate was partitioned, and aqueous layer was extracted with methylene chloride. The organic layers were combined, and the combined organic layer was dried over sodium sulfate anhydrate. The solvent was distilled away under reduced pressure, and the resultant residue was purified by silica gel flash column chromatography (methylene chloride:methanol=100:7→10:1), to thereby give the title compound (110 mg).

1. concentrationThe reaction mixture was concentrated under reduced pressure
2. additionwere added methylene chloride (50 mL) and saturated aqueous sodium hydrogencarbonate (200 mL)
3. filtrationThe precipitated colorless solid was filtered off
4. customThe filtrate was partitioned
5. extractionaqueous layer was extracted with methylene chloride
6. dry with materialthe combined organic layer was dried over sodium sulfate anhydrate
7. distillationThe solvent was distilled away under reduced pressure
8. customthe resultant residue was purified by silica gel flash column chromatography (methylene chloride:methanol=100:7→10:1)