Dichloromethane → 3-(4-(1H-Imidazol-1-yl)benzyl)-2,4-dichloro-6-iodoquinoline

HRID 926473Notes

Reaction equation

HRID 926473 reaction equation
[N:1]1([C:6]2[CH:25]=[CH:24][C:9]([CH2:10][C:11]3C(O)=[N:13][C:14]4[C:19]([C:20]=3O)=[CH:18][C:17]([I:22])=[CH:16][CH:15]=4)=[CH:8][CH:7]=2)[CH:5]=[CH:4][N:3]=[CH:2]1.P(Cl)(Cl)([Cl:28])=O.Cl[CH2:32][Cl:33].C(=O)(O)[O-].[Na+]>C(#N)C>[N:1]1([C:6]2[CH:25]=[CH:24][C:9]([CH2:10][C:11]3[C:32]([Cl:33])=[N:13][C:14]4[C:19]([C:20]=3[Cl:28])=[CH:18][C:17]([I:22])=[CH:16][CH:15]=4)=[CH:8][CH:7]=2)[CH:5]=[CH:4][N:3]=[CH:2]1

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 24813Phosphorus oxychlorideHCID 516892Sodium BicarbonateHCID 178517226HCID 178517226, compound

Product 1

HCID 1180062873-(4-(1H-Imidazol-1-yl)benzyl)-2,4-dichloro-6-iodoquinoline

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
23 °C

Procedure

A mixture containing 3-(4-(1H-imidazol-1-yl)benzyl)-6-iodoquinoline-2,4-diol (3.0 g, 6.8 mmol, Intermediate 17: step a) and phosphorus oxychloride (1.9 mL, 20 mmol) in acetonitrile (34 mL) was heated to 100° C. After 16 hours, the flask was allowed to cool to 23° C. Dichloromethane (200 mL) and saturated aqueous sodium bicarbonate solution were added in sequence and the resulting biphasic mixture was stirred for 30 minutes. The biphasic mixture was filtered through Celite® and the layers of the biphasic filtrate were separated. The organic layer was dried with magnesium sulfate and the dried solution was filtered. Silica gel (7 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 dichloromethane initially, grading to 5% methanol-dichloromethane provided the title compound as a solid.

Workup

  1. filtrationThe biphasic mixture was filtered through Celite®
  2. customthe layers of the biphasic filtrate were separated
  3. dry with materialThe organic layer was dried with magnesium sulfate
  4. filtrationthe dried solution was filtered
  5. additionSilica gel (7 g) was added to the filtrate
  6. customthe solvent was removed by rotary evaporation
  7. customto afford a free-flowing powder
  8. customThe powder was loaded onto a column of silica gel for purification
  9. washElution with dichloromethane initially

Sources & evidence

ORD record
ord-97bc11b1c4e44a3aa83fd9229a35d43a
Source dataset
uspto-grants-2016_03
Patent number
US09284308B2

Reaction notes

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