反应详情

5-((2S,4R)-1-acetyl-4-amino-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)picolinic acid (for a preparation, see Intermediate 55) (510 mg, 1.567 mmol), morpholine (0.149 mL, 1.72 mmol), HATU (656 mg, 1.724 mmol) and DIPEA (0.821 mL, 4.70 mmol) were combined in DMF (5 mL) and the mixture stirred at room temperature overnight. Morpholine (0.149 mL, 1.72 mmol) was added and the reaction stirred at room temperature for a further 3 h. The mixture was concentrated in vacuo before being dissolved in DCM and loaded onto an aminopropyl SPE column (50 g). The column was eluted with 10% MeOH in DCM and the appropriate fractions were combined and concentrated in vacuo to give a residue. This residue was purified by chromatography (50 g column, 2M methanolic ammonia/DCM gradient) to give 1-((2S,4R)-4-amino-2-methyl-6-(6-(morpholine-4-carbonyl)pyridin-3-yl)-3,4-dihydroquinolin-1(2H)-yl)ethanone (470 mg, 1.19 mmol, 76% yield) as a beige solid. LCMS: (Formate, 2 min), Rt=0.48 mins, MH+=395.

1. stirringthe reaction stirred at room temperature for a further 3 h
2. concentrationThe mixture was concentrated in vacuo
3. dissolutionbefore being dissolved in DCM
4. washThe column was eluted with 10% MeOH in DCM
5. concentrationconcentrated in vacuo
6. customto give a residue
7. customThis residue was purified by chromatography (50 g column, 2M methanolic ammonia/DCM gradient)