反应详情

A solution of 3.0 g (17.6 mmol) 6-chloro-N-methyl-nicotinamide in 42.0 ml THF was treated at 4° C. dropwise over 15 min. with 43.8 ml (43.8 mmol) o-tolylmagnesiumchloride-solution (1M in THF). The reaction mixture was stirred for 2 h at r.t., cooled to 0° C. and treated dropwise with 50 ml 5% aqueous NH4Cl. The aqueous phase was separated and extracted twice with toluene and the organic phases were washed twice with 5% aqueous NH4Cl. The combined organic phases were dried over Na2SO4 and filtrated. The filtrate was treated with 9.8 ml (88.3 mmol) 1-methylpiperazine and stirred for 1.5 h at r.t. The reaction mixture was treated with 40 ml 5% aqueous NH4Cl and the pH adjusted with NaOH (28%) to 10. The aqueous phase was separated and extracted twice with CH2Cl2 and the organic phases were washed twice with brine. The combined organic phases were dried over Na2SO4 and filtrated. The solvent was removed under reduced pressure to yield 5.4 g (94.6 %) product as yellowish crystals, m.p. 137.0-138.0° C.

1. temperaturecooled to 0° C.
2. customThe aqueous phase was separated
3. extractionextracted twice with toluene
4. washthe organic phases were washed twice with 5% aqueous NH4Cl
5. dry with materialThe combined organic phases were dried over Na2SO4
6. filtrationfiltrated
7. stirringstirred for 1.5 h at r.t
8. customThe aqueous phase was separated
9. extractionextracted twice with CH2Cl2
10. washthe organic phases were washed twice with brine
11. dry with materialThe combined organic phases were dried over Na2SO4
12. filtrationfiltrated
13. customThe solvent was removed under reduced pressure