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

HRID 348019
Notes
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Reaction equation

HRID 348019 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]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 4

HCID 24813Phosphorus oxychlorideHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 178432046HCID 178432046, compound

Product 1

HCID 210837207-Chloro-3-(4-chlorophenyl)-2-(2-chlorophenyl)-5,6-dimethylpyrazolo[1,5-a]pyrimidine

Reagents, catalysts & solvents 2

HCID 1140
Toluene
Solvent
HCID 8857Ethyl AcetateSolvent

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

  1. temperaturecooled to room temperature
  2. customThe aqueous layer was separated
  3. extractionextracted with additional ethyl acetate
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried (MgSO4)
  6. 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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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes