Phosphorus oxychloride → 7-Chloro-3-(4-chlorophenyl)-2-(2-chlorophenyl)-5,6-dimethylpyrazolo[1,5-a]pyrimidine

HRID 348019Notes

Reaction equation

[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[Cl:26])=[N:10][N:11]3[C:16](O)=[C:15]([CH3:18])[C:14]([CH3:19])=[N:13][C:12]=23)=[CH:4][CH:3]=1.C(N(C(C)C)CC)(C)C.O=P(Cl)(Cl)[Cl:38].C(=O)(O)[O-].[Na+]>C1(C)C=CC=CC=1.C(OCC)(=O)C>[Cl:38][C:16]1[N:11]2[N:10]=[C:9]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[Cl:26])[C:8]([C:5]3[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=3)=[C:12]2[N:13]=[C:14]([CH3:19])[C:15]=1[CH3:18]

Participants

Conditions

Temperature: 100 °C

Procedure

To a slurry of 3-(4-chlorophenyl)-2-(2-chlorophenyl)-5,6-dimethyl-pyrazolo[1,5-a]pyrimidin-7-ol (I-4A-1a; 0.277 g, 0.721 mmol) and diisopropylethylamine (0.188 ml, 1.08 mmol) in toluene (7.2 ml) at room temperature was added POCl3 (0.336 ml, 3.60 mmol), dropwise. The mixture was heated at 100° C. for 7 hours, cooled to room temperature, and then slowly added to a stirred mixture of ice, saturated aqueous sodium bicarbonate and ethyl acetate. The aqueous layer was separated and extracted with additional ethyl acetate. The combined organic layers were washed with brine, dried (MgSO4), and then concentrated, in vacuo, to afford the crude product. Purification on a Biotage™ Flash 40S column using 0–8% ethyl acetate in hexanes as eluant afforded I-4A-1b (146 mg, 50%) as a yellow solid: +ESI MS (M+1) 402.0; 1H NMR (400 MHz, CD2Cl2) δ 7.55–7.35 (m, 6H), 7.25 (d, J=8.7 Hz, 2H), 2.66 (s, 3H), 2.47 (s, 3H).

Workup

temperaturecooled to room temperature
customThe aqueous layer was separated
extractionextracted with additional ethyl acetate
washThe combined organic layers were washed with brine
dry with materialdried (MgSO4)
concentrationconcentrated, in vacuo

Sources & evidence

ORD record: ord-0c1c1afe2eda4cedae7124e7a8916d24
Source dataset: uspto-grants-2007_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07176210B2

Reaction notes

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