Triethylamine → 7-Chloro-2-(2-chlorophenyl)-pyrazolo[1,5-a]pyrimidine

HRID 347999Notes

Reaction equation

[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:17]=[C:11]2[NH:12][CH:13]=[CH:14][C:15](=O)[N:10]2[N:9]=1.C(N(CC)CC)C.O=P(Cl)(Cl)[Cl:27].C(=O)(O)[O-].[Na+]>C1(C)C=CC=CC=1.C(OCC)(=O)C>[Cl:27][C:15]1[N:10]2[N:9]=[C:8]([C:3]3[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=3[Cl:1])[CH:17]=[C:11]2[N:12]=[CH:13][CH:14]=1

Participants

Conditions

Temperature: 95 °C

Procedure

To a slurry of 2-(2-chlorophenyl)-4H-pyrazolo[1,5-a]pyrimidin-7-one (I-1A-1b; 30.0 g, 122 mmol) and triethylamine (25.5 ml, 183 mmol) in toluene (1.3 liters) at room temperature was added POCl3 (58 ml, 0.62 mol), dropwise. The mixture was heated at 95° C. for 4 hours, cooled to room temperature, then slowly added to a stirred mixture of ice, sodium bicarbonate (300 g) and ethyl acetate (1 liter), keeping the temperature at 0° C. The aqueous layer was separated and extracted with additional ethyl acetate. The combined organic layers were dried (MgSO4), and then concentrated, in vacuo, to afford an amber solid. This material was purified by silica gel chromatography using 2:1:0.1 methylene chloride/hexanes/methanol as eluant to afford I-1A-1c as a colorless solid (17.5 g, 54%): +APcI MS (M+1) 264.2; 1H NMR (400 MHz, CD2Cl2) δ 8.40 (d, J=4.6 Hz, 1H), 8.00–7.97 (m, 1H), 7.56–7.53 (m, 1H), 7.45–7.39 (m, 2H), 7.34 (s, 1), 7.03 (d, J=4.6 Hz, 1H).

Workup

temperaturecooled to room temperature
customat 0° C
customThe aqueous layer was separated
extractionextracted with additional ethyl acetate
dry with materialThe combined organic layers were dried (MgSO4)
concentrationconcentrated, in vacuo
customto afford an amber solid
customThis material was purified by silica gel chromatography

Sources & evidence

ORD record: ord-0378a2aa30bf4e4b94059ff8756422fc
Source dataset: uspto-grants-2007_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07176210B2

Reaction notes

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