Toluene → 4-(3-(4-(1H-1,2,4-Triazol-1-yl)benzyl)-4-chloro-2-methoxyquinoline-6-carbonyl)benzonitrile

HRID 926472Notes

Reaction equation

HRID 926472 reaction equation
[N:1]1([C:6]2[CH:34]=[CH:33][C:9]([CH2:10][C:11]3[C:12](Cl)=[N:13][C:14]4[C:19]([C:20]=3[Cl:21])=[CH:18][C:17]([C:22]([C:24]3[CH:31]=[CH:30][C:27]([C:28]#[N:29])=[CH:26][CH:25]=3)=[O:23])=[CH:16][CH:15]=4)=[CH:8][CH:7]=2)[CH:5]=[N:4][CH:3]=[N:2]1.[CH3:35][O-:36].[Na+].C1(C)C=CC=CC=1>ClCCl>[N:1]1([C:6]2[CH:34]=[CH:33][C:9]([CH2:10][C:11]3[C:12]([O:36][CH3:35])=[N:13][C:14]4[C:19]([C:20]=3[Cl:21])=[CH:18][C:17]([C:22]([C:24]3[CH:31]=[CH:30][C:27]([C:28]#[N:29])=[CH:26][CH:25]=3)=[O:23])=[CH:16][CH:15]=4)=[CH:8][CH:7]=2)[CH:5]=[N:4][CH:3]=[N:2]1

Participants

5

Reactant 3

HCID 1140TolueneHCID 10942334Sodium MethoxideHCID 1180061164-(3-(4-(1H-1,2,4-Triazol-1-yl)benzyl)-2,4-dichloroquinoline-6-carbonyl)benzonitrile2×

Product 1

HCID 1180062474-(3-(4-(1H-1,2,4-Triazol-1-yl)benzyl)-4-chloro-2-methoxyquinoline-6-carbonyl)benzonitrile

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
110 °C

Procedure

A heterogeneous mixture containing 4-(3-(4-(1H-1,2,4-triazol-1-yl)benzyl)-2,4-dichloroquinoline-6-carbonyl)benzonitrile (583 mg, 1.20 mmol, Intermediate 16: step d), sodium methoxide (780 mg, 14.4 mmol), and toluene (17 mL) was heated to 110° C. After 45 minutes, the flask was allowed to cool to 23° C. Dichloromethane (100 mL) was added to the flask and then the mixture was filtered through Celite®, rinsing with dichloromethane. Silica gel (5 g) was added to the filtrate and the solvent was removed by rotary evaporation to provide a free-flowing powder. The powder was loaded onto a column of silica gel for flash chromatography purification. Elution with hexanes initially, grading to 80% ethyl acetate-hexanes afforded the title compound as a white solid.

Workup

  1. temperatureto cool to 23° C
  2. filtrationthe mixture was filtered through Celite®
  3. washrinsing with dichloromethane
  4. additionSilica gel (5 g) was added to the filtrate
  5. customthe solvent was removed by rotary evaporation
  6. customto provide a free-flowing powder
  7. customThe powder was loaded onto a column of silica gel for flash chromatography purification
  8. washElution with hexanes initially

Sources & evidence

ORD record
ord-43c9cdc7298b47b2b3acd154e0b487ee
Source dataset
uspto-grants-2016_03
Patent number
US09284308B2

Reaction notes

Loading…