反应详情

4-[(3-Chloro-2-methylphenyl)carbonyl]-2-piperazinone (I134) (185 mg, 0.732 mmol) was suspended in dry Dichloromethane (DCM) (3 mL) before treating with trimethyloxonium tetrafluoroborate (137 mg, 0.879 mmol) and stirring for 16 hours at RT, under argon before adding 1,3-thiazole-2-carbohydrazide (I51) (157 mg, 1.098 mmol) and stirring for a further 4 hours. 1-Butanol (3.00 mL) was added then DCM was removed by evaporation and the residue was heated at 110° C. for 3 hours. The reaction was cooled to RT overnight and then worked up by diluting with DCM (50 ml), washing with saturated sodium bicarbonate solution (50 ml). The aqueous layer was extracted with DCM (2×30 ml), the combined extracts were washed with brine (30 ml), dried (MgSO4), filtered and evaporated to afford an orange gum, of crude material which was purified by MDAP. The desired fractions were isolated, combined and evaporated to afford a white solid, 125 mg. This was dried over the weekend at 40° C. and then dried overnight in a vacuum oven at 40° C. to afford the white solid of desired product in 115 mg.

1. stirringstirring for a further 4 hours
2. customDCM was removed by evaporation
3. temperaturethe residue was heated at 110° C. for 3 hours
4. temperatureThe reaction was cooled to RT overnight
5. additionby diluting with DCM (50 ml)
6. washwashing with saturated sodium bicarbonate solution (50 ml)
7. extractionThe aqueous layer was extracted with DCM (2×30 ml)
8. washthe combined extracts were washed with brine (30 ml)
9. dry with materialdried (MgSO4)
10. filtrationfiltered
11. customevaporated
12. customto afford an orange gum
13. customof crude material which was purified by MDAP
14. customThe desired fractions were isolated
15. customevaporated
16. customto afford a white solid, 125 mg
17. customThis was dried over the weekend at 40° C.
18. customdried overnight in a vacuum oven at 40° C.