反应详情

A mixture of 5-amino-6-chloro-2-ethylimidazo[1,2-a]pyridine-8-carboxylic acid (EXAMPLE 10, Step 2, 10.00 g, 41.72 mmol), tert-butyl 4-(aminomethyl)piperidine-1-carboxylate (J. Prugh, L. A. Birchenough and M. S. Egbertson, Synth. Commun., 1992, 22, 2357-60) (15.20 g, 70.93 mmol), diethyl phosphorocyanidate (10.76 mL, 70.93 mmol) and diisopropylethylamine (18.17 mL, 104.4 mmol) in N,N-dimethylformamide (267 mL) was stirred at room temperature for 43 h. The solvent was removed by evaporation. The residue was basified with aqueous sodium bicarbonate (40 mL), and extracted with dichloromethane (5×100 mL). The combined extract was washed with brine, dried over magnesium sulfate, and concentrated in vacuo. Flash chromatography of the residue eluting with dichloromethane/methanol (100:1 to 20:1) afforded 19.08 g (90%) of the title compound as a yellow oil.

1. customThe solvent was removed by evaporation
2. extractionextracted with dichloromethane (5×100 mL)
3. extractionThe combined extract
4. washwas washed with brine
5. dry with materialdried over magnesium sulfate
6. concentrationconcentrated in vacuo
7. washFlash chromatography of the residue eluting with dichloromethane/methanol (100:1 to 20:1)