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

HRID 348008Notes

Reaction equation

[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:18]=[C:11]2[N:12]=[C:13]([CH3:17])[CH:14]=[C:15](O)[N:10]2[N:9]=1.C(N(CC)CC)C.O=P(Cl)(Cl)[Cl:28].C(=O)(O)[O-].[Na+]>C1(C)C=CC=CC=1.C(OCC)(=O)C>[Cl:28][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:18]=[C:11]2[N:12]=[C:13]([CH3:17])[CH:14]=1

Participants

Conditions

Temperature: 95 °C

Procedure

To a slurry of 2-(2-chlorophenyl)-5-methylpyrazolo[1,5-a]pyrimidin-7-ol (I-1A-3f; 700 mg, 2.70 mmol) and triethylamine (0.57 ml, 4.0 mmol) in toluene (30 ml) at room temperature was added POCl3 (1.3 ml, 14 mmol), dropwise. The mixture was heated at 95° C. for 21 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 (0.79 g). Purification on a Biotage™ Flash 40S column using 0–20% ethyl acetate in hexanes as eluant afforded I-1A-3g as an off-white solid (643 mg, 86%): +ESI MS (M+1) 278.12; 1H NMR (400 MHz, CD2Cl2) δ 7.96–7.93 (m, 1H), 7.54–7.51 (m, 1H), 7.50–7.35 (m, 2H), 7.15 (s, 1H), 6.90 (s, 1H), 2.59 (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
customto afford the crude product (0.79 g)
customPurification on a Biotage™ Flash 40S column

Sources & evidence

ORD record: ord-79ae36246ee447cca58a24f69a7bae81
Source dataset: uspto-grants-2007_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07176210B2

Reaction notes

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