Aluminum(III) Chloride → HCID 57743043, compound

Reaction equation

Cl[CH2:2][N:3]1[CH2:7][CH:6]([CH:8]=[C:9]([F:11])[F:10])[CH2:5][C:4]1=[O:12].[Al+3].[Cl-].[Cl-].[Cl-].[Cl:17][C:18]1[CH:23]=[CH:22][N:21]2[N:24]=[C:25]([CH:27]3[CH2:29][CH2:28]3)[CH:26]=[C:20]2[N:19]=1>O1CCOCC1>[Cl:17][C:18]1[CH:23]=[CH:22][N:21]2[N:24]=[C:25]([CH:27]3[CH2:29][CH2:28]3)[C:26]([CH2:2][N:3]3[CH2:7][CH:6]([CH:8]=[C:9]([F:11])[F:10])[CH2:5][C:4]3=[O:12])=[C:20]2[N:19]=1

Participants

Procedure

To a solution of 1-(chloromethyl)-4-(2,2-difluorovinyl)pyrrolidin-2-one x276 (2.55 mmol, 2 eq, 500 mg) in 15 ml of dioxane at 0° C. are added successively AlCl3 (5.1 mmol, 2 eq, 680 mg) and 5-chloro-2-cyclopropylpyrazolo[1,5-a]pyrimidine x274 (2.55 mmol, 1 eq, 495 mg). The mixture is stirred at reflux for 1 hour, then quenched with an aqueous saturated NH4Cl solution and the resulting mixture extracted with AcOEt. The cumulated organic layers are washed with water, dried over MgSO4, filtered and evaporated under reduced pressure. The crude product is purified by chromatography on silicagel (CH2Cl2/MeOH/NH4OH: 98/2/0.2), followed by a crystallization step in hexane. 1-[(5-chloro-2-cyclopropylpyrazolo[1,5-a]pyrimidin-3-yl)methyl]-4-(2,2-difluorovinyl)pyrrolidin-2-one 219 is obtained as a solid (623 mg).