Sodium hydride → HCID 68304566, compound

HRID 2199316Notes

Reaction equation

HRID 2199316 reaction equation
C(OP([CH2:9][C:10]1[N:11]=[CH:12][C:13]([NH:16][C:17](=[O:23])[O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[N:14][CH:15]=1)(OCC)=O)C.[H-].[Na+].[CH:26]([C:28]1[CH:29]=[C:30]([NH:35][C:36](=[O:55])[C:37]2[CH:42]=[CH:41][C:40]([CH2:43][N:44]3[CH2:49][CH2:48][N:47]([CH3:50])[CH2:46][CH2:45]3)=[C:39]([C:51]([F:54])([F:53])[F:52])[CH:38]=2)[CH:31]=[CH:32][C:33]=1[CH3:34])=O>CN(C=O)C>[CH3:34][C:33]1[CH:32]=[CH:31][C:30]([NH:35][C:36](=[O:55])[C:37]2[CH:42]=[CH:41][C:40]([CH2:43][N:44]3[CH2:49][CH2:48][N:47]([CH3:50])[CH2:46][CH2:45]3)=[C:39]([C:51]([F:53])([F:54])[F:52])[CH:38]=2)=[CH:29][C:28]=1/[CH:26]=[CH:9]/[C:10]1[N:11]=[CH:12][C:13]([NH:16][C:17](=[O:23])[O:18][C:19]([CH3:20])([CH3:21])[CH3:22])=[N:14][CH:15]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 59649414HCID 59649414, compoundHCID 86676738HCID 86676738, compound

Product 1

HCID 68304566HCID 68304566, compoundYield 65.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

tert-butyl 5-((diethoxyphosphoryl)methyl)pyrazin-2-ylcarbamate (35 mg, 0.10 mmol) in dried DMF (0.5 mL) was added NaH (5 mg, 0.12 mmol) at 0° C. After 20 minutes, a solution N-(3-formyl-4-methylphenyl)-4-((4-methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)benzamide (44 mg, 0.10 mmol) in dried DMF (0.5 mL) was added slowly into the reaction mixture. The reaction mixture was stirred overnight at room temperature and quenched by adding water. The reaction mixture was partitioned between ethyl acetate and water. The organic layer was separated and the aqueous layer was extracted with ethyl acetate. The combined organic extracts were washed with brine, dried over MgSO4, celite filtered and concentrated under reduced pressure. The crude product was purified by flash chromatography using (3% to 7% MeOH/CH2Cl2) as a solvent to afford title compound (40 mg, 64% yield). MS m/z: 611 [M+1].

Workup

  1. customquenched
  2. additionby adding water
  3. customThe reaction mixture was partitioned between ethyl acetate and water
  4. customThe organic layer was separated
  5. extractionthe aqueous layer was extracted with ethyl acetate
  6. washThe combined organic extracts were washed with brine
  7. dry with materialdried over MgSO4, celite
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe crude product was purified by flash chromatography

Sources & evidence

ORD record
ord-8494a39618ef4984bdebd81290958d23
Source dataset
uspto-grants-2016_06
Patent number
US09358231B2

Reaction notes

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