反应详情

温度

25 °C

A suspension of the trifluoroacetic acid salt of 4-amino-piperidine-1-carboxylic acid (7-methoxy-thiazolo[5,4-d]pyrimidin-2-yl)-amide (1.82 g, 4.30 mmol) in methanol was treated with N,N-diisopropylethylamine (1.5 mL, 6.50 mmol), 4-fluoro-3-(trifluoromethyl)benzaldehyde (1.3 mL, 6.50 mmol) and toluene. The resulting mixture was stirred at 25° C. for 1 h and was then concentrated in vacuo. This procedure was repeated until the reaction mixture became homogenous when dissolved in toluene. After the final concentration to remove toluene, the reaction mixture was diluted with dichloroethane (100 mL) and then was treated with acetic acid (0.26 g) and sodium triacetoxyborohydride (2.73 g, 13 mmol). The resulting reaction mixture was allowed to stir at 25° C. overnight. At this time, the reaction mixture was poured into water and extracted into ethyl acetate. The organics were washed with a saturated aqueous sodium bicarbonate solution, dried over sodium sulfate, filtered and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, gradient elution 1:1 ethyl acetate/hexanes) afforded a colorless oil. The oil was dissolved in diethyl ether and then was concentrated in vacuo to afford 4-(4-fluoro-3-trifluoromethyl-benzylamino)-piperidine-1-carboxylic acid (7-methoxy-thiazolo[5,4-d]pyrimidin-2-yl)-amide (530 mg, 25%) as a white, foamy solid; ES-HRMS m/e calcd for C20H20F4N6O2S (M+H)+ 485.1378, found 485.1378.

1. concentrationwas then concentrated in vacuo
2. dissolutiondissolved in toluene
3. concentrationAfter the final concentration
4. customto remove toluene
5. additionthe reaction mixture was diluted with dichloroethane (100 mL)
6. customThe resulting reaction mixture
7. stirringto stir at 25° C. overnight
8. extractionextracted into ethyl acetate
9. washThe organics were washed with a saturated aqueous sodium bicarbonate solution
10. dry with materialdried over sodium sulfate
11. filtrationfiltered
12. concentrationconcentrated in vacuo
13. washFlash chromatography (Merck Silica gel 60, 230-400 mesh, gradient elution 1:1 ethyl acetate/hexanes)
14. customafforded a colorless oil
15. concentrationwas concentrated in vacuo