反应详情

Combine (R)-2-((4-(3-(difluoromethyl)-4-fluorophenyl)-2-(piperidin-4-yl)-1H-imidazol-1-yl)methyl)-1-methylpiperidine (0.8 g, 0.0018 mol, 1.0 eq); 4-chloro-5-ethyl-5,7 dihydro-pyrrolo[2,3-d]pyrimidin-6-one (0.425 g, 0.00216 mol, 1.2 eq); DIPEA (2.3 mL, 0.0126 mol, 7.0 eq) and IPA (15 mL) in a pressure tube and heat at 120° C. overnight under sealed condition. Cool the reaction mass and dilute with water (25 mL). Extract in EA (2×50 mL) and wash the organic layer with brine (2×50 mL). Dry over anhydrous sodium sulfate and concentrate the crude compound. Filter the crude product through a short silica pad (100-200 mesh) using 0-8% MeOH-DCM). LCMS of concentrated crude product shows 70% of the desired product (m/z=568 [M+H]). Purify through reverse phase preparative HPLC to get 0.055 g of the title compound. MS (ES+): m/z=568 (M+H).

1. customunder sealed condition
2. temperatureCool the reaction mass
3. extractionExtract in EA (2×50 mL)
4. washwash the organic layer with brine (2×50 mL)
5. dry with materialDry over anhydrous sodium sulfate
6. concentrationconcentrate the crude compound
7. filtrationFilter the crude product through a short silica pad (100-200 mesh)
8. concentrationLCMS of concentrated crude product
9. customPurify through reverse phase preparative HPLC