N,N-Diethylaniline → 3-Bromo-7-chloro-6-(4-phenylpiperidine-1-carbonyl)pyrazolo[1,5-a]pyrimidine

Reaction equation

[Br:1][C:2]1[CH:3]=[N:4][N:5]2[C:10](O)=[C:9]([C:12]([N:14]3[CH2:19][CH2:18][CH:17]([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=4)[CH2:16][CH2:15]3)=[O:13])[CH:8]=[N:7][C:6]=12.C(N(CC)C1C=CC=CC=1)C.P(Cl)(Cl)([Cl:39])=O>>[Br:1][C:2]1[CH:3]=[N:4][N:5]2[C:10]([Cl:39])=[C:9]([C:12]([N:14]3[CH2:19][CH2:18][CH:17]([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=4)[CH2:16][CH2:15]3)=[O:13])[CH:8]=[N:7][C:6]=12

Participants

Reactant 3

HCID 7061N,N-Diethylaniline

HCID 24813Phosphorus oxychloride

HCID 178519790HCID 178519790, compound

Product 1

HCID 866462893-Bromo-7-chloro-6-(4-phenylpiperidine-1-carbonyl)pyrazolo[1,5-a]pyrimidineYield 93%

Procedure

To 3-bromo-7-hydroxy-6-(4-phenylpiperidine-1-carbonyl)pyrazolo[1,5-a]pyrimidine (7.7 g, 19.1 mmol) obtained in step 2 were added phosphorus oxychloride (100 mL) and N,N-diethylaniline (6.1 mL, 38.3 mmol), and the mixture was heated under reflux for 5 hr. The reaction mixture was concentrated under reduced pressure, the residue was diluted with ethyl acetate (100 mL) and neutralized with saturated aqueous sodium hydrogen carbonate solution (300 mL) under ice-cooling, and the organic layer and the aqueous layer were separated. The organic layer was washed with 10% aqueous citric acid solution (50 mL) and saturated brine (100 mL), dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=2/1) to give the title compound (7.5 g, 93%).