反应详情

To a solution of 2.5 g (7.7 mmol) N-methyl-6-(4-methyl-piperazin-1-yl)-4-o-tolyl-nicotinamide in 51 ml THF at 4° C. was added dropwise over 30 min 10.2 ml (10.2 mmol) potassium bis(trimethylsilyl) amide (1M in THF). The reaction mixture was stirred for 30 min and subsequently treated at 4° C. dropwise over 30 min with 1.46 ml (7.7 mmol) 3,5-bis-trifluoromethyl-benzylbromide. The reaction mixture was stirred for 1.5 h at 4° C., treated with 31 ml water and extracted. The aqueous phase was separated and adjusted to pH 12 with 2N NaOH and subsequently extracted with 30 ml ethyl acetate. The aqueous phase was separated, the combined organic phases were dried over Na2SO4, the solvent was removed under reduced pressure and the residue purified by chromatography over silica gel (CH2CG2: MeOH=99:1) to yield 3.6 g (84.1%) product as beige foam.

1. stirringThe reaction mixture was stirred for 1.5 h at 4° C.
2. extractionextracted
3. customThe aqueous phase was separated
4. extractionsubsequently extracted with 30 ml ethyl acetate
5. customThe aqueous phase was separated
6. dry with materialthe combined organic phases were dried over Na2SO4
7. customthe solvent was removed under reduced pressure
8. customthe residue purified by chromatography over silica gel (CH2CG2: MeOH=99:1)