反应详情

温度

25 °C

A solution of 4-oxo-piperidine-1-carboxylic acid (7-methoxy-thiazolo[5,4-d]pyrimidin-2-yl)-amide (as prepared in Example 59, 100 mg, 0.33 mmol) in tetrahydrofuran (35 mL) cooled to 0° C. was treated with 3-chlorophenyl magnesium bromide (0.5 M in tetrahydrofuran, 1.6 mL, 0.8 mmol). The resulting mixture was stirred at 25° C. for 3 h. At this time, the reaction mixture was cooled to 0° C. and was treated with an additional amount of 3-chlorophenyl magnesium bromide (0.5 M in tetrahydrofuran, 6 mL, 3.0 mmol). The mixture was then allowed to warm to 25° C. and to stir at 25° C. overnight. At this time, the reaction was quenched with methanol and absorbed onto silica gel (6 g). ISCO chromatography (120 g, Silica, gradient elution 7/93 methanol/methylene chloride) afforded 4-(3-chloro-phenyl)-4-hydroxy-piperidine-1-carboxylic acid (7-methoxy-thiazolo[5,4-d]pyrimidin-2-yl)-amide (61 mg, 44%) as a light brown solid; LRMS for C18H18ClN5O3S (M+H)+ at m/z=420. The NMR spectrum obtained on the sample is compatible with its structure.

1. temperatureAt this time, the reaction mixture was cooled to 0° C.
2. temperatureto warm to 25° C.
3. stirringto stir at 25° C. overnight
4. customAt this time, the reaction was quenched with methanol
5. customabsorbed onto silica gel (6 g)
6. washISCO chromatography (120 g, Silica, gradient elution 7/93 methanol/methylene chloride)