反应详情

To a solution of 2,4-dichloropyrimidine (2.307, 15.49 mmol) and TEA (2.15 mL, 15.49 mmol) in EtOH (19.36 mL) at −10° C. was added (R)-piperidine-3-carboxylic acid (Sigma Aldrich, 2 g, 15.49 mmol). The reaction was allowed to slowly warm to room temperature while stirring. After 20 hours, the reaction was concentrated. The residue was adsorbed onto a plug of silica gel and purified by chromatography through a 100 g silica gel column, eluting with 2% to 10% MeOH in DCM followed by 20% to 50% 5:45:50 folic acid:EtOH:DCM, to provide M4.1 as a white solid in 21% yield. 1H NMR (400 MHz, CD3OD) δ ppm 1.51-1.63 (m, 1H) 1.76-1.91 (m, 2H) 2.09 (dd, J=8.71, 4.40 Hz, 1H) 2.51-2.60 (m, 1H) 3.33-3.51 (m, 3H) 4.01 (br. s., 1H) 6.74 (d, J=6.46 Hz, 1H) 7.96 (d, J=6.26 Hz, 1H); ESI-MS M+H 241.9.

1. concentrationthe reaction was concentrated
2. custompurified by chromatography through a 100 g silica gel column
3. washeluting with 2% to 10% MeOH in DCM
4. customEtOH:DCM, to provide M4.1 as a white solid in 21% yield