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

HRID 348017Notes

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)=[CH:15][C:14]([CH3:18])=[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]=[C:14]([CH3:18])[CH:15]=1

Participants

Conditions

Temperature: 100 °C

Procedure

To a slurry of 3-(4-chlorophenyl)-2-(2-chlorophenyl)-5-methylpyrazolo[1,5-a]pyrimidin-7-ol (I-3A-4a; 1.08 g, 2.92 mmol) and diisopropylethylamine (0.763 ml, 4.38 mmol) in toluene (30 ml) at room temperature was added POCl3 (1.36 ml, 14.6 mmol), dropwise. The mixture was heated at 100° C. for 16 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. Purification on a Biotage™ Flash 40M column using 0–10% ethyl acetate in hexanes as eluant afforded I-3A-4b (1.05 g, 92%) as a yellow solid: +ESI MS (M+1) 388.1; 1H NMR (400 MHz, CD2Cl2) δ 7.55–7.35 (m, 6H), 7.26 (d, J=8.7 Hz, 2H), 6.98 (s, 1H), 2.64 (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-81854e5c1d8f4f958afb6f25a08880d6
Source dataset: uspto-grants-2007_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07176210B2

Reaction notes

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