Sodium hydride → 4-(3-Fluorophenyl)-6-methoxy-1-[(1-methyl-1H-1,2,4-triazol-5-yl)methyl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile

HRID 1169691Notes

Reaction equation

HRID 1169691 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:8]2[C:17]3[C:12](=[CH:13][CH:14]=[C:15]([O:18][CH3:19])[CH:16]=3)[NH:11][C:10](=[O:20])[C:9]=2[C:21]#[N:22])[CH:5]=[CH:6][CH:7]=1.[H-].[Na+].[Br-].[Li+].CS(O[CH2:32][C:33]1[N:37]([CH3:38])[N:36]=[CH:35][N:34]=1)(=O)=O>COCCOC.CN(C)C=O>[F:1][C:2]1[CH:3]=[C:4]([C:8]2[C:17]3[C:12](=[CH:13][CH:14]=[C:15]([O:18][CH3:19])[CH:16]=3)[N:11]([CH2:32][C:33]3[N:37]([CH3:38])[N:36]=[CH:35][N:34]=3)[C:10](=[O:20])[C:9]=2[C:21]#[N:22])[CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 82050Lithium BromideHCID 114151654-(3-Fluorophenyl)-6-methoxy-2-oxo-1,2-dihydroquinoline-3-carbonitrileHCID 86611705(1-Methyl-1H-1,2,4-triazol-5-yl)methyl methanesulfonate

Product 1

HCID 112921974-(3-Fluorophenyl)-6-methoxy-1-[(1-methyl-1H-1,2,4-triazol-5-yl)methyl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 80711,2-DimethoxyethaneSolvent

Procedure

To a solution of 4-(3-fluorophenyl)-6-methoxy-2-oxo-1,2-dihydroquinoline-3-carbonitrile (46.0 mg, 0.156 mmol) in 2 mL of 1,2-dimethoxyethane and 0.5 mL of N,N-dimethylformamide at 0° C. was added sodium hydride (8.0 mg of 60% dispersion in mineral oil, 0.23 mmol). After 10 minutes, lithium bromide was added (27 mg, 0.31 mmol), and the reaction was stirred for one hour. A solution of (1-Methyl-1H-1,2,4-triazol-5-yl)methyl methanesulfonate (33 mg, 0.17 mmol) in 0.5 mL of N,N-dimethylformamide was added, and the reaction was allowed to warm to room temperature. After one hour, the reaction was quenched with water and partitioned between EtOAc and water, and the organic layer was washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was crystallized from EtOAc/hexane to provide the titled product. 1H NMR, difference nOe, and HMQC NMR spectral data for the product were consistent with the titled compound. HRMS (ES) exact mass calculated for C21H16FN5O2 (M+H+): 390.1361. Found 390.1409.

Workup

  1. waitAfter one hour
  2. customthe reaction was quenched with water
  3. custompartitioned between EtOAc and water
  4. washthe organic layer was washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude product was crystallized from EtOAc/hexane

Sources & evidence

ORD record
ord-7e4f0cc441654e72afbd66604359f890
Source dataset
uspto-grants-2010_11
Patent number
US07825131B2

Reaction notes

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