Water → 2-((4-(1,3-dimethyl-4-(pyridin-4-yl)-1H-pyrazol-5-yl)phenoxy)methyl)quinoline

HRID 33924Notes

Reaction equation

HRID 33924 reaction equation
[CH3:1][C:2]1[C:6]([C:7]2[CH:12]=[CH:11][N:10]=[CH:9][CH:8]=2)=[C:5]([C:13]2[CH:30]=[CH:29][C:16]([O:17][CH2:18][C:19]3[CH:28]=[CH:27][C:26]4[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=4)[N:20]=3)=[CH:15][CH:14]=2)[NH:4][N:3]=1.[H-].[Na+].[CH3:33]I.O>CN(C)C=O>[CH3:33][N:4]1[C:5]([C:13]2[CH:30]=[CH:29][C:16]([O:17][CH2:18][C:19]3[CH:28]=[CH:27][C:26]4[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=4)[N:20]=3)=[CH:15][CH:14]=2)=[C:6]([C:7]2[CH:8]=[CH:9][N:10]=[CH:11][CH:12]=2)[C:2]([CH3:1])=[N:3]1

Participants

6

Reactant 4

HCID 962WaterHCID 6328Methyl iodideHCID 24758Sodium hydride2×HCID 178434588HCID 178434588, compound

Product 1

HCID 116829072-((4-(1,3-dimethyl-4-(pyridin-4-yl)-1H-pyrazol-5-yl)phenoxy)methyl)quinoline

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 2-((4-(3-methyl-4-(pyridin-4-yl)-1H-pyrazol-5-yl)phenoxy)methyl)quinoline (150 mg, 0.38 mmol) in anhydrous dimethylformamide (2 mL) was treated at 0° C. with sodium hydride dispersion (30 mg, 0.76 mmol of 60% NaH in oil) followed after 20 min with methyl iodide (54 mg, 0.38 mmol), and the stirred mixture was allowed to warm to RT overnight. Water was added and the mixture extracted with dichloromethane (3×20 mL). The organic layer was dried, concentrated, and the residue chromatographed on silica eluted with an ethyl acetate-hexane gradient containing 1% triethylamine, giving fractions containing two isomeric substances. The less polar isomer (18 mg) was thus obtained (methylation regiochemistry tentatively assigned by NMR). 1H NMR (CDCl3, 400 mHz) δ 8.41 (m, 2H), 8.21 (d, 1H, J=8.7 Hz), 8.07 (d, 1H, J=8.3 Hz), 7.84 (d, 1H, J=9.5 Hz), 7.74 (ddd, 1H), 7.67 (d, 1H, J=8.3 Hz), 7.55 (ddd, 1H), 7.12 (m, 2H), 7.05 (m, 2H), 7.0 (m, 2H), 5.40 (s, 2H), 3.71 (s, 3H), 2.37 (s, 3H). HPLC-MS 4.81 min, m/e 407 (MH+).

Workup

  1. extractionthe mixture extracted with dichloromethane (3×20 mL)
  2. customThe organic layer was dried
  3. concentrationconcentrated
  4. customthe residue chromatographed on silica
  5. washeluted with an ethyl acetate-hexane gradient
  6. additioncontaining 1% triethylamine
  7. customgiving fractions
  8. additioncontaining two isomeric substances
  9. customThe less polar isomer (18 mg) was thus obtained (methylation regiochemistry
  10. customHPLC-MS 4.81 min, m/e 407 (MH+)

Sources & evidence

ORD record
ord-0649a21e453c4f4e850264e6ee35f856
Source dataset
uspto-grants-2008_09
Patent number
US07429665B2

Reaction notes

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