Hexane → {[6-Chloro-2-(trifluoromethyl)imidazo[1,2-b]pyridazin-3-yl]methyl}-4-(2,2-difluoro-vinyl)-pyrrolidin-2-one

Sodium hydride (60% wt mineral oil dispersion, 0.82 g, 1.3 eq, 20.5 mmol) is washed three times by hexane (15 ml). THF (15 ml) is added at room temperature to this clean sodium hydride, a solution of 4-(2,2-difluorovinyl)pyrrolidin-2-one x98 (3.42 g, 23 mmol, 1.4 eq) and 3-(bromomethyl)-6-chloro-2-(trifluoromethyl)imidazo[1,2-b]pyridazine x36 (4.97 mg, 15.8 mmol, 1 eq) in THF (15 ml). After 3 hours of stirring at room temperature, a small amount of sodium hydride is added in order to complete the reaction and stirring is pursue overnight. Water (25 ml) is then added to the mixture and THF is removed evaporation under reduced pressure. The aqueous layer is extracted by ethyl acetate (2×50 ml), the resulting organic layer is dried over MgSO4, filtered and concentrated to dryness. The residue is purified by preparative chromatography (benzine/AcOEt: 50/50) to afford 4.33 g of {[6-chloro-2-(trifluoromethyl)imidazo[1,2-b]pyridazin-3-yl]methyl}-4-(2,2-difluoro-vinyl)-pyrrolidin-2-one 33.

1. customthe reaction
2. stirringstirring
3. waitis pursue overnight
4. customis removed
5. customevaporation under reduced pressure
6. extractionThe aqueous layer is extracted by ethyl acetate (2×50 ml)
7. dry with materialthe resulting organic layer is dried over MgSO4
8. filtrationfiltered
9. concentrationconcentrated to dryness
10. customThe residue is purified by preparative chromatography (benzine/AcOEt: 50/50)

ORDレコード

ord-910f903c575a42ec9531b45b60defdef

出典データセット

uspto-grants-2013_11

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08586623B2