Sodium hydride → 2-{[4-Chloro-3-(trifluoromethyl)phenyl]oxy}-5-[({1-[(1-methyl-1H-pyrazol-4-yl)methyl]-2-oxo-1,2-dihydro-4-pyridinyl}oxy)methyl]benzonitrile

HRID 536197Notes

Reaction equation

HRID 536197 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:9]2[CH:16]=[CH:15][C:14]([CH2:17][O:18][C:19]3[CH:24]=[CH:23][NH:22][C:21](=[O:25])[CH:20]=3)=[CH:13][C:10]=2[C:11]#[N:12])=[CH:4][C:3]=1[C:26]([F:29])([F:28])[F:27].[H-].[Na+].Cl[CH2:33][C:34]1[CH:35]=[N:36][N:37]([CH3:39])[CH:38]=1>CN(C)C=O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:9]2[CH:16]=[CH:15][C:14]([CH2:17][O:18][C:19]3[CH:24]=[CH:23][N:22]([CH2:33][C:34]4[CH:35]=[N:36][N:37]([CH3:39])[CH:38]=4)[C:21](=[O:25])[CH:20]=3)=[CH:13][C:10]=2[C:11]#[N:12])=[CH:4][C:3]=1[C:26]([F:29])([F:27])[F:28]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 21698362HCID 21698362, compoundHCID 679586692-{[4-Chloro-3-(trifluoromethyl)phenyl]oxy}-5-{[(2-oxo-1,2-dihydro-4-pyridinyl)oxy]methyl}benzonitrile

Product 1

HCID 679666632-{[4-Chloro-3-(trifluoromethyl)phenyl]oxy}-5-[({1-[(1-methyl-1H-pyrazol-4-yl)methyl]-2-oxo-1,2-dihydro-4-pyridinyl}oxy)methyl]benzonitrileYield 18.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-{[4-Chloro-3-(trifluoromethyl)phenyl]oxy}-5-{[(2-oxo-1,2-dihydro-4-pyridinyl)oxy]methyl}benzonitrile (60 mg, 0.143 mmol) in N,N-dimethylformamide (2 mL) was added Sodium hydride (40 mg, 1.00 mmol) at rt in one portion. After stirring at rt for 10 min, 4-(chloromethyl)-1-methyl-1H-pyrazole (40 mg, 0.306 mmol) was added. The reaction mixture was heated at 60° C. in the microwave for 30 min, then quenched by addition of methanol, concentrated. Purification via Biotage-C18 system afforded the title product (13.6 mg) as a white solid. LC-MS (ESI): m/z 515 [M+H]+; 3.36 min (ret time).

Workup

  1. temperatureThe reaction mixture was heated at 60° C. in the microwave for 30 min
  2. customquenched by addition of methanol
  3. concentrationconcentrated
  4. customPurification via Biotage-C18 system

Sources & evidence

ORD record
ord-a7028efdf1d24c94bd5f57c48979b9d8
Source dataset
uspto-grants-2014_10
Patent number
US08859573B2

Reaction notes

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