反应详情

1-Benzyl-4-[N-methyl-N-(3-isopropylamino-6-chloro-2-pyridinyl)amino]piperidine (EXAMPLE 184, 1.60 g, 4.84 mmol) is dissolved in dichloromethane (0.2M) and cooled to 0°. 1-Chloroethyl-chloroformate (0.57 ml, 5.32 mmol) is added dropwise. The mixture is allowed to warm to 20°-25°, then refluxed one half hour. The solvent is removed to one third volume, 15 ml methanol is added and the mixture is refluxed 2 hr. Extraction with chloroform, drying the extract over sodium sulfate and removal of the solvent gives the crude product. Flash column chromatography (silica gel, 100 g; methanol/chloroform (10/90)) gives the title compound, NMR (300 MHz, CD3OD) 6.88, 3.49, 3.23, 2.87, 2.50, 1.95, 1.70 and 1.12δ.

1. temperaturecooled to 0°
2. temperatureto warm to 20°-25°
3. temperaturerefluxed one half hour
4. customThe solvent is removed to one third volume, 15 ml methanol
5. additionis added
6. temperaturethe mixture is refluxed 2 hr
7. extractionExtraction with chloroform
8. customdrying the
9. extractionextract over sodium sulfate and removal of the solvent
10. customgives the crude product