反应详情

A stirred solution of 6-(1,1-difluoro-butyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-c]pyridine (100 mg, 0.42 mmol) in DCM (5 mL) and pyridine (0.5 mL) at 0° C. was treated with chloroacetyl chloride (0.036 mL, 0.46 mmol). After 2 h the solution was treated with (2R,5S)-2-methyl-5-morpholin-4-ylmethyl-piperazine-1-carboxylic acid tert-butyl ester (124 mg, 0.42 mmol) and further pyridine (0.5 mL). After overnight stirring at room temperature no coupling had occurred: the mixture was concentrated in vacuo, diluted with DMF (3 mL), treated with DMAP (1 mg) and heated to 75° C. After 6 h, LC/MS showed ˜80% progression. The mixture was cooled and partitioned between DCM and water. The aqueous phase was extracted with DCM. The combined organic phases were dried (Na2SO4), filtered and concentrated to dryness. Purification by preparative HPLC gave a pale brown glass (30 mg, 12%). MS: [M+H]+=580

1. concentrationthe mixture was concentrated in vacuo
2. additiondiluted with DMF (3 mL)
3. additiontreated with DMAP (1 mg)
4. temperatureheated to 75° C
5. waitAfter 6 h
6. temperatureThe mixture was cooled
7. custompartitioned between DCM and water
8. extractionThe aqueous phase was extracted with DCM
9. dry with materialThe combined organic phases were dried (Na2SO4)
10. filtrationfiltered
11. concentrationconcentrated to dryness
12. customPurification by preparative HPLC