反应详情

To a stirred 0° C. solution of 1-(azetidin-3-ylcarbonyl)-4-cyclobutyl-1,4-diazepane (20 mg, 0.084 mmol) in DCM (1 ml) and TEA (0.023 ml, 0.17 mmol) was added dropwise piperidine-1-carbonyl chloride (14.9 mg, 0.013 ml, 0.10 mmol). The reaction was stirred for 1 h and then allowed to warm to RT and the progress monitored by LCMS. After 1 h the reaction was quenched with water (5 ml), extracted with DCM (2×10 ml), dried (MgSO4), filtered and concentrated at reduced pressure. Purification by silica FCC (eluting with 99:1 to 96:4 gradient of DCM/2M NH3 in MeOH) provided impure title compound (22 mg, 78%) as brown oil. Re-purification by preparative HPLC provided the title compound (3 mg, 10% yield) as a colourless oil.

1. customAfter 1 h the reaction was quenched with water (5 ml)
2. extractionextracted with DCM (2×10 ml)
3. dry with materialdried (MgSO4)
4. filtrationfiltered
5. concentrationconcentrated at reduced pressure
6. customPurification
7. washby silica FCC (eluting with 99:1 to 96:4 gradient of DCM/2M NH3 in MeOH)