反应详情

Acetyl chloride (1 mol/l in DCM, 13 ml, 13 mmol) is added to a mixture of methyl 3-amino-4,5-dimethyl-1H-pyrrole-2-carboxylate N9a (2.2 g, 12.1 mmol), DIPEA (4.5 ml, 26.5 mmol) and DCM (40 ml) at 0° C. under stirring. The mixture is warmed to RT and stirring continued for 1 hour. Saturated aqueous solution of NaHCO3 is added and the precipitate collected. The aqueous phase is extracted with DCM. The combined organic layers are dried over MgSO4, concentrated in vacuo and pooled with the precipitate. DCM (35 ml) and benzyltriethylammonium bromide (645 mg, 2.37 mmol) is added and the mixture cooled to 0° C. Sodium hydroxide (50% in water, 15 ml) and dimethylsulfate (1.4 g, 11.2 mmol) is added and stirring continued at 0° C. for 1 hour. Water is added and the mixture extracted with DCM. The combined organic layers are dried over MgSO4 and concentrated in vacuo. Concentrated aqueous ammonia (20 ml) is added and the mixture heated to 100° C. in a microwave for 30 hours. The mixture is concentrated in vacuo and the crude product (0.59 g) used without further purification. HPLC-MS: M+H=192; tR=0.62 min (METHOD—1).

1. stirringstirring
2. customthe precipitate collected
3. extractionThe aqueous phase is extracted with DCM
4. dry with materialThe combined organic layers are dried over MgSO4
5. concentrationconcentrated in vacuo
6. temperaturethe mixture cooled to 0° C
7. stirringstirring
8. waitcontinued at 0° C. for 1 hour
9. extractionthe mixture extracted with DCM
10. dry with materialThe combined organic layers are dried over MgSO4
11. concentrationconcentrated in vacuo
12. additionConcentrated aqueous ammonia (20 ml) is added
13. temperaturethe mixture heated to 100° C. in a microwave for 30 hours
14. concentrationThe mixture is concentrated in vacuo
15. customthe crude product (0.59 g) used without further purification