Ethyl 4-chloroacetoacetate → 5-(Chloromethyl)-1-phenylpyrazolo[1,5-a]pyrimidin-7(1H)-one

HRID 1154534Notes

Reaction equation

[NH2:1][C:2]1[CH:6]=[CH:5][N:4]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[N:3]=1.[Cl:13][CH2:14][C:15](=O)[CH2:16][C:17](OCC)=[O:18]>[OH-].[Na+]>[Cl:13][CH2:14][C:15]1[N:1]=[C:2]2[CH:6]=[CH:5][N:4]([C:7]3[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=3)[N:3]2[C:17](=[O:18])[CH:16]=1

Participants

Conditions

Temperature: 100 °C

Procedure

3-amino-1-phenyl-pyrazole (4 g) was reacted with ethyl 4-chloro-acetoacetate (4.1 g) in polyphosphoric acid (19.8 g; 10.6 g of H3PO4 and 9.2 g of P2O5) under stirring at 100° C. for 30 minutes: after cooling the reaction mixture was diluted with ice water and neutralized with 35% NaOH. The precipitate was filtered and washed with water to give 5-chloromethyl-1-phenyl-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one, m.p. 194°-196° C. (5.9 g), which was reacted with triphenylphosphine (6.75 g) in acetonitrile (190 ml) at reflux temperature for 65 hours. After cooling the solution was evaporated in vacuo to dryness and the residue was treated with ethyl acetate: filtration of the crystalline product gave (1-phenyl-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one-5-yl)-methyl-triphenylphosphonium chloride, m.p. 245°-247° C. (10 g), which was dissolved in chloroform (100 ml) and added dropwise to a suspension of 75% NaH (0.74 g) in chloroform (50 ml) and dimethylsulphoxide (5 ml) mantaining the temperature under 20° C.

Workup

temperatureafter cooling the reaction mixture
filtrationThe precipitate was filtered
washwashed with water

Sources & evidence

ORD record: ord-75f0c40631bd464982d03ec1b43d7e39
Source dataset: uspto-grants-1984_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US04490376

Reaction notes

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