Sodium Methoxide → (3-(4-(1H-Pyrazol-1-yl)benzyl)-4-chloro-2-methoxyquinolin-6-yl)(3-fluorophenyl)(pyridin-3-yl)methanol

HRID 926604Notes

Reaction equation

HRID 926604 reaction equation
[N:1]1([C:6]2[CH:39]=[CH:38][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:30]3[CH:35]=[CH:34][CH:33]=[C:32]([F:36])[CH:31]=3)([C:24]3[CH:25]=[N:26][CH:27]=[CH:28][CH:29]=3)[OH:23])=[CH:16][CH:15]=4)=[CH:8][CH:7]=2)[CH:5]=[CH:4][CH:3]=[N:2]1.[CH3:40][O-:41].[Na+]>C1(C)C=CC=CC=1>[N:1]1([C:6]2[CH:39]=[CH:38][C:9]([CH2:10][C:11]3[C:12]([O:41][CH3:40])=[N:13][C:14]4[C:19]([C:20]=3[Cl:21])=[CH:18][C:17]([C:22]([C:30]3[CH:35]=[CH:34][CH:33]=[C:32]([F:36])[CH:31]=3)([C:24]3[CH:25]=[N:26][CH:27]=[CH:28][CH:29]=3)[OH:23])=[CH:16][CH:15]=4)=[CH:8][CH:7]=2)[CH:5]=[CH:4][CH:3]=[N:2]1

Participants

4

Reactant 2

HCID 10942334Sodium MethoxideHCID 74220811(3-(4-(1H-Pyrazol-1-yl)benzyl)-2,4-dichloroquinolin-6-yl)(3-fluorophenyl)(pyridin-3-yl)methanol2×

Product 1

HCID 118006728(3-(4-(1H-Pyrazol-1-yl)benzyl)-4-chloro-2-methoxyquinolin-6-yl)(3-fluorophenyl)(pyridin-3-yl)methanol

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
105 °C

Procedure

(3-(4-(1H-Pyrazol-1-yl)benzyl)-2,4-dichloroquinolin-6-yl)(3-fluorophenyl)(pyridin-3-yl)methanol (16.2 mg, 0.0292 mmol, Intermediate 36) and sodium methoxide (8.0 mg, 0.15 mmol) were charged to a microwave vial with dry toluene (0.14 mL) and heated to 105° C. for 4 hours. The mixture was allowed to cool to room temperature, then filtered through Celite® and rinsed with dichloromethane. The filtrate was concentrated to dryness and purified by reverse-phase chromatography (acetonitrile/H2O+0.05% TFA). The isolated product fractions were basified with saturated aqueous sodium bicarbonate, extracted with DCM, dried (Na2SO4), filtered, and concentrated to dryness to provide the title compound. 1H NMR (400 MHz, CDCl3) δ 8.58 (s, 2H), 8.03 (d, J=2.0 Hz, 1H), 7.85 (d, J=2.4 Hz, 1H), 7.81 (d, J=8.8 Hz, 1H), 7.70-7.66 (m, 2H), 7.58-7.51 (m, 3H), 7.35 (d, J=8.7 Hz, 2H), 7.33-7.28 (m, 2H), 7.09-7.04 (m, 2H), 7.04-6.99 (m, 1H), 6.45-6.41 (m, 1H), 4.31 (s, 2H), 4.08 (s, 3H); MS m/e 551.2 [M+H]+.

Workup

  1. temperatureto cool to room temperature
  2. filtrationfiltered through Celite®
  3. washrinsed with dichloromethane
  4. concentrationThe filtrate was concentrated to dryness
  5. custompurified by reverse-phase chromatography (acetonitrile/H2O+0.05% TFA)
  6. extractionextracted with DCM
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-dc72f9f247f746359433c0ba3b29eecb
Source dataset
uspto-grants-2016_03
Patent number
US09284308B2

Reaction notes

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