N,N-Dimethylaniline → 7-Chloropyrazolo[1,5-a]pyrimidine
Reaction equation
[N:1]1[N:5]2[C:6](O)=[CH:7][CH:8]=[N:9][C:4]2=[CH:3][CH:2]=1.O=P(Cl)(Cl)[Cl:13].CN(C)C1C=CC=CC=1>>[Cl:13][C:6]1[N:5]2[N:1]=[CH:2][CH:3]=[C:4]2[N:9]=[CH:8][CH:7]=1Participants
4
Procedure
To a solution of pyrazolo[1,5-a]pyrimidin-7-ol (C-1) (19.0 g, 14.1 mmol, 1.0 eq) in phosphoroxychloride (100 mL, 1.06 mol, 76 eq) at RT, N,N-dimethylaniline (7.0 g, 58.0 mmol, 4.1 eq) is added dropwise and the resulting mixture is stirred at reflux overnight. The mixture is allowed to cool to RT and concentrated in vacuo to remove the phosphoroxychloride. The residue is poured into ice water (200 mL), neutralized with saturated aqueous NaHCO3 solution to adjust the pH to 8-9 while keeping the temperature below 5° C. The mixture is stirred at RT for 30 min and then extracted with ethyl acetate (4×200 mL). The combined organic layers are washed with brine, dried over Na2SO4 and filtered. The filtrate is concentrated in vacuo and the residue is purified by flash column chromatography on silica gel (1-3% ethyl acetate-petroleum ether) to afford the product, 7-chloropyrazolo[1,5-a]pyrimidine (C-2).