Dichloromethane → HCID 23502786, compound

HRID 1835360Notes

Reaction equation

HRID 1835360 reaction equation
[F:1][C:2]([F:34])([F:33])[C:3]1[CH:4]=[C:5]([CH:26]=[C:27]([C:29]([F:32])([F:31])[F:30])[CH:28]=1)[CH2:6][N:7]([CH3:25])[C:8](=[O:24])[C:9]1[C:14]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[CH3:21])=[CH:13][C:12]([CH2:22]O)=[N:11][CH:10]=1.ClCCl.[H-].[Na+].[CH3:40][C:41]1[NH:42][CH:43]=[CH:44][N:45]=1>CN(C)C=O>[F:1][C:2]([F:33])([F:34])[C:3]1[CH:4]=[C:5]([CH:26]=[C:27]([C:29]([F:31])([F:30])[F:32])[CH:28]=1)[CH2:6][N:7]([CH3:25])[C:8](=[O:24])[C:9]1[C:14]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[CH3:21])=[CH:13][C:12]([CH2:22][N:42]2[CH:43]=[CH:44][N:45]=[C:41]2[CH3:40])=[N:11][CH:10]=1

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 127492-MethylimidazoleHCID 24758Sodium hydrideHCID 10299574HCID 10299574, compound

Product 1

HCID 23502786HCID 23502786, compoundYield 46%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 100 mg (0.207 mmol) N-(3,5-bis-trifluoromethyl-benzyl)-6-hydroxymethyl-N-methyl-4-o-tolyl-nicotinamide (Example 7) in 1 ml dichloromethane 0.03 ml (0.4 mmol) thionyl chloride were added at 0° C. The reaction mixture was allowed to warm to room temperature and stirred for 1 h. The solvent was evaporated and the light yellow residue was dried in high vacuo. The residue was dissolved in 1 ml dry N,N-dimethylformamide and added to a suspension of 2-methylimidazole sodium salt that had previously been prepared by addition of 54 mg (1.2 mmol) sodium hydride (55% dispersion in mineral oil) to a solution of 52 mg (0.62 mmol) 2-methylimidazole in 3 ml dry N,N-dimethylformamide under argon at room temperature. After stirring for 3 h the reaction was quenched by addition of excess water, followed by extraction with three portions of ethyl acetate. The combined organic extracts were dried with sodium sulfate and concentrated. Column chromatography afforded 52 mg (46%) of the title compound as an orange solid.

Workup

  1. customThe solvent was evaporated
  2. customthe light yellow residue was dried in high vacuo
  3. dissolutionThe residue was dissolved in 1 ml dry N,N-dimethylformamide
  4. additionadded to a suspension of 2-methylimidazole sodium salt that
  5. stirringAfter stirring for 3 h the reaction
  6. customwas quenched by addition of excess water
  7. extractionfollowed by extraction with three portions of ethyl acetate
  8. dry with materialThe combined organic extracts were dried with sodium sulfate
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-65c9b0145ec440d6b72227a5bff97800
Source dataset
uspto-grants-2004_08
Patent number
US06770637B2

Reaction notes

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