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

HRID 348012Notes

Reaction equation

[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=3[Cl:25])=[N:10][N:11]3[C:16](O)=[C:15]([CH3:18])[CH:14]=[N:13][C:12]=23)=[CH:4][CH:3]=1.C(N(C(C)C)CC)(C)C.O=P(Cl)(Cl)[Cl:37].C(=O)(O)[O-].[Na+]>C1(C)C=CC=CC=1.C(OCC)(=O)C>[Cl:37][C:16]1[N:11]2[N:10]=[C:9]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=3[Cl:25])[C:8]([C:5]3[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=3)=[C:12]2[N:13]=[CH:14][C:15]=1[CH3:18]

Participants

Conditions

Temperature: 100 °C

Procedure

To a slurry of 3-(4-chlorophenyl)-2-(2-chlorophenyl)-6-methylpyrazolo[1,5-a]pyrimidin-7-ol (I-3A-1c; 119 mg, 0.321 mmol) and diisopropylethylamine (0.084 ml, 0.48 mmol) in toluene (2.2 ml) at room temperature was added POCl3 (0.15 ml, 1.61 mmol), dropwise. The mixture was heated at 100° C. for 22 hours, cooled to room temperature, 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 (120 mg). Purification on a Biotage™ Flash 12M column using 0–8% ethyl acetate in hexanes as eluant afforded I-3A-1d (102 mg, 82%) as a yellow solid: +ESI MS (M+1) 388.1; 1H NMR (400 MHz, CD2Cl2) δ 8.44 (s, 1H), 7.55–7.37 (m, 6H), 7.27 (d, J=8.7 Hz, 2H), 2.51 (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-5801f25949b749378094f28ccf0ab942
Source dataset: uspto-grants-2007_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07176210B2

Reaction notes

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