反应详情

To a cooled (0° C.) solution of (2R)-5-amino-1,3-dihydrospiro[indene-2,3′-pyrrolo[2,3-b]pyridin]-2′(1′H)-one (0.100 g, 0.398 mmol, Intermediate 9) and triethylamine (100. μL, 0.716 mmol) in THF (8 mL) was added bromoacetyl bromide (46.0 μL, 0.523 mmol). After allowing the reaction to warm to ambient temperature, triethylamine (0.230 mL, 1.67 mmol) and methyl 1-{[(3S)-3-amino-3-phenylpropyl]amino}cyclopentanecarboxylate bis-hydrochloride (0.139 g, 0.398 mmol, Intermediate 38) were added, prior to heating the reaction to 50° C. for 17 h. After cooling to ambient temperature, the reaction mixture was diluted with chloroform and saturated aqueous sodium bicarbonate. The aqueous layer was extracted twice with additional chloroform. The combined organics were dried over sodium sulfate, filtered and concentrated in vacuo to give an oil. This oil was purified by silica gel chromatography, eluting with a gradient of CH2Cl2:MeOH:NH4OH—99:1:0.1 to 92:8:0.8, to give the title compound. MS: m/z=568 (M+1).

1. customthe reaction
2. temperatureto heating
3. customthe reaction to 50° C. for 17 h
4. temperatureAfter cooling to ambient temperature
5. extractionThe aqueous layer was extracted twice with additional chloroform
6. dry with materialThe combined organics were dried over sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. customto give an oil
10. customThis oil was purified by silica gel chromatography
11. washeluting with a gradient of CH2Cl2