Ammonium Chloride → (3-(4-(1H-Pyrazol-1-yl)benzyl)-4-chloro-2-methoxy-8-methylquinolin-6-yl)bis(1-methyl-1H-imidazol-5-yl)methanol

HRID 928842

Reaction equation

HRID 928842 reaction equation
C([Li])CCC.[N:6]1([C:11]2[CH:32]=[CH:31][C:14]([CH2:15][C:16]3[C:17]([O:29][CH3:30])=[N:18][C:19]4[C:24]([C:25]=3[Cl:26])=[CH:23][C:22](Br)=[CH:21][C:20]=4[CH3:28])=[CH:13][CH:12]=2)[CH:10]=[CH:9][CH:8]=[N:7]1.[CH3:33][N:34]1[C:38]([C:39]([C:41]2[N:45]([CH3:46])[CH:44]=[N:43][CH:42]=2)=[O:40])=[CH:37][N:36]=[CH:35]1.[NH4+].[Cl-]>C1COCC1.O.CCOC(C)=O>[N:6]1([C:11]2[CH:32]=[CH:31][C:14]([CH2:15][C:16]3[C:17]([O:29][CH3:30])=[N:18][C:19]4[C:24]([C:25]=3[Cl:26])=[CH:23][C:22]([C:39]([C:38]3[N:34]([CH3:33])[CH:35]=[N:36][CH:37]=3)([C:41]3[N:45]([CH3:46])[CH:44]=[N:43][CH:42]=3)[OH:40])=[CH:21][C:20]=4[CH3:28])=[CH:13][CH:12]=2)[CH:10]=[CH:9][CH:8]=[N:7]1

Participants

8

Reactant 4

HCID 25517Ammonium ChlorideHCID 22048478Bis(1-methyl-1H-imidazol-5-yl)methanone2×HCID 867155993-(4-(1H-Pyrazol-1-yl)benzyl)-6-bromo-4-chloro-2-methoxy-8-methylquinoline2×HCID 178418339Butyllithium

Product 1

HCID 74220881(3-(4-(1H-Pyrazol-1-yl)benzyl)-4-chloro-2-methoxy-8-methylquinolin-6-yl)bis(1-methyl-1H-imidazol-5-yl)methanol

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

n-Butyllithium (1.6 M in hexane; 0.5 mL, 0.718 mmol) was added dropwise to a suspension of the 3-(4-(1H-pyrazol-1-yl)benzyl)-6-bromo-4-chloro-2-methoxy-8-methylquinoline (0.29 g, 0.653 mmol, Intermediate 19: step b) in dry THF (4 mL) over a 2 minute period at −78° C. A heterogeneous mixture of bis(1-methyl-1H-imidazol-5-yl)methanone (0.14 g, 0.653 mmol, Intermediate 39: step b) in THF (3 mL) was added as a slurry and stirring was continued at −78° C. for 5 minutes. The resulting homogeneous mixture was warmed up to 0° C. and stirred for 10 minutes. The mixture was warmed to room temperature and saturated aqueous NH4Cl was added followed by EtOAc. H2O was added and layers were separated. The aqueous layer was again extracted with EtOAc and the combined organic extracts washed with brine, dried over Na2SO4, filtered, evaporated to dryness. The crude product was purified by chromatography (10% MeOH in CH2Cl2; gradient) to provide the title compound. 1H NMR (400 MHz, CDCl3) δ ppm 7.95-8.04 (m, 1H), 7.79-7.89 (m, 1H), 7.65-7.71 (m, 1H), 7.50-7.60 (m, 2H), 7.34-7.45 (m, 5H), 7.32 (s, 1H), 6.36-6.52 (m, 2H), 4.31 (s, 2H), 4.10 (s, 3H), 3.53 (s, 6H), 2.62 (s, 3H). mass calcd. C30H28ClN7O2, 554.05; m/z found, 554.2

Workup

  1. additionwas added as a slurry
  2. stirringstirred for 10 minutes
  3. temperatureThe mixture was warmed to room temperature
  4. customlayers were separated
  5. extractionThe aqueous layer was again extracted with EtOAc
  6. washthe combined organic extracts washed with brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. customevaporated to dryness
  10. customThe crude product was purified by chromatography (10% MeOH in CH2Cl2; gradient)

Sources & evidence

ORD record
ord-4f1e2f95c4324e97821e6f0d09916dab
Source dataset
uspto-grants-2016_03
Patent number
US09290476B2

Linked notes

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