Sodium hydride → 4-[({4-[4-cyclopropyl-2-(2-trifluoromethoxy-phenyl)-2H-pyrazol-3-ylmethoxy]-2-methyl-phenyl}-methyl-amino)-methyl]-2-methoxy-benzoic acid methyl ester

HRID 2261869Notes

Reaction equation

HRID 2261869 reaction equation
[H-].[Na+].[CH:3]1([C:6]2[CH:10]=[N:9][N:8]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[O:17][C:18]([F:21])([F:20])[F:19])[C:7]=2[CH2:22][O:23][C:24]2[CH:29]=[CH:28][C:27]([NH:30][CH3:31])=[C:26]([CH3:32])[CH:25]=2)[CH2:5][CH2:4]1.[CH3:33][O:34][C:35](=[O:46])[C:36]1[CH:41]=[CH:40][C:39]([CH2:42]Br)=[CH:38][C:37]=1[O:44][CH3:45]>CN(C=O)C.O>[CH3:33][O:34][C:35](=[O:46])[C:36]1[CH:41]=[CH:40][C:39]([CH2:42][N:30]([C:27]2[CH:28]=[CH:29][C:24]([O:23][CH2:22][C:7]3[N:8]([C:11]4[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=4[O:17][C:18]([F:20])([F:21])[F:19])[N:9]=[CH:10][C:6]=3[CH:3]3[CH2:4][CH2:5]3)=[CH:25][C:26]=2[CH3:32])[CH3:31])=[CH:38][C:37]=1[O:44][CH3:45]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 11288398Methyl 4-(bromomethyl)-2-methoxybenzoateHCID 57443372{4-[4-Cyclopropyl-2-(2-trifluoromethoxy-phenyl)-2H-pyrazol-3-ylmethoxy]-2-methyl-phenyl}-methyl-amine

Product 1

HCID 675285424-[({4-[4-cyclopropyl-2-(2-trifluoromethoxy-phenyl)-2H-pyrazol-3-ylmethoxy]-2-methyl-phenyl}-methyl-amino)-methyl]-2-methoxy-benzoic acid methyl esterYield 68%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
40 °C

Procedure

Sodium hydride (60% in mineral oil, 30 mg, 0.75 mmol) is added to a solution of {4-[4-cyclopropyl-2-(2-trifluoromethoxy-phenyl)-2H-pyrazol-3-ylmethoxy]-2-methyl-phenyl}-methyl-amine (0.31 g, 0.75 mmol) and 4-bromomethyl-2-methoxy-benzoic acid methyl ester (0.320 g, 1.23 mmol) in DMF (3 mL) at room temperature. The reaction is heated to 40° C. for 2 h. The mixture is diluted with water and is extracted with ethyl acetate. The combined organic layers are washed with brine and dried over MgSO4. The crude residue is purified via radial chromatography (2 mm plate, 20 to 40 THF-heptane) to afford 4-[({4-[4-cyclopropyl-2-(2-trifluoromethoxy-phenyl)-2H-pyrazol-3-ylmethoxy]-2-methyl-phenyl}-methyl-amino)-methyl]-2-methoxy-benzoic acid methyl ester (303 mg, 68%). ES/MS m/e 596.0 (M+1).

Workup

  1. extractionis extracted with ethyl acetate
  2. washThe combined organic layers are washed with brine
  3. dry with materialdried over MgSO4
  4. customThe crude residue is purified via radial chromatography (2 mm plate, 20 to 40 THF-heptane)

Sources & evidence

ORD record
ord-4f5488de012c4c929a05300be613ddee
Source dataset
uspto-grants-2010_12
Patent number
US07846960B2

Reaction notes

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