Phosphorus oxychloride → HCID 118006213, compound

HRID 926499Notes

Reaction equation

HRID 926499 reaction equation
[N:1]1([C:6]2[CH:26]=[CH:25][C:9]([CH2:10][C:11]3[C:12]([CH2:23][CH3:24])=[N:13][C:14]4[C:19]([C:20]=3O)=[CH:18][C:17]([Br:22])=[CH:16][CH:15]=4)=[CH:8][CH:7]=2)[CH:5]=[CH:4][CH:3]=[N:2]1.P(Cl)(Cl)([Cl:29])=O>C(#N)C>[N:1]1([C:6]2[CH:26]=[CH:25][C:9]([CH2:10][C:11]3[C:12]([CH2:23][CH3:24])=[N:13][C:14]4[C:19]([C:20]=3[Cl:29])=[CH:18][C:17]([Br:22])=[CH:16][CH:15]=4)=[CH:8][CH:7]=2)[CH:5]=[CH:4][CH:3]=[N:2]1

Participants

4

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 178437401HCID 178437401, compound2×

Product 1

HCID 118006213HCID 118006213, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
90 °C

Procedure

A mixture containing 3-(4-(1H-pyrazol-1-yl)benzyl)-6-bromo-2-ethylquinolin-4-ol (1.78 g, 4.36 mmol, Intermediate 32: step c) and phosphorus oxychloride (1.8 mL, 20 mmol) in acetonitrile (15 mL) was heated to 90° C. After 3 hours, the flask was allowed to cool to 23° C. The mixture was concentrated. Dichloromethane (100 mL) and ice (50 mL) were added to the residue. Concentrated aqueous ammonia solution was added dropwise with stirring until the pH was 9 by litmus paper test. The biphasic mixture was stirred at 23° C. for 30 minutes. The layers were separated. The aqueous layer was extracted with dichloromethane (25 mL). The organic layers were combined and the combined solution was dried with sodium sulfate. The dried solution was filtered. Celite® (8 g) was added to the filtrate and the solvent was removed by rotary evaporation to afford a free-flowing powder. The powder was loaded onto a column of silica gel for purification. Elution with hexanes initially, grading to 25% ethyl acetate-hexanes provided the title compound as an off-white solid.

Workup

  1. temperatureto cool to 23° C
  2. concentrationThe mixture was concentrated
  3. additionDichloromethane (100 mL) and ice (50 mL) were added to the residue
  4. additionConcentrated aqueous ammonia solution was added dropwise
  5. stirringThe biphasic mixture was stirred at 23° C. for 30 minutes
  6. customThe layers were separated
  7. extractionThe aqueous layer was extracted with dichloromethane (25 mL)
  8. dry with materialthe combined solution was dried with sodium sulfate
  9. filtrationThe dried solution was filtered
  10. additionCelite® (8 g) was added to the filtrate
  11. customthe solvent was removed by rotary evaporation
  12. customto afford a free-flowing powder
  13. customThe powder was loaded onto a column of silica gel for purification
  14. washElution with hexanes initially

Sources & evidence

ORD record
ord-74160fbe1f5c4d588982468497fc02c8
Source dataset
uspto-grants-2016_03
Patent number
US09284308B2

Reaction notes

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