Sodium hydride → 1-Benzyl-4-(6-(4-fluorophenyl)-4,5-dimethylpyridazin-3-yl)-3-methylpiperazin-2-one

HRID 2093364Notes

Reaction equation

HRID 2093364 reaction equation
[CH2:1]([N:8]([CH2:14][CH2:15][NH:16][C:17]1[N:18]=[N:19][C:20]([C:25]2[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=2)=[C:21]([CH3:24])[C:22]=1[CH3:23])[C:9](=[O:13])[C@H:10](Cl)[CH3:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+]>C1COCC1>[CH2:1]([N:8]1[CH2:14][CH2:15][N:16]([C:17]2[N:18]=[N:19][C:20]([C:25]3[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=3)=[C:21]([CH3:24])[C:22]=2[CH3:23])[CH:10]([CH3:11])[C:9]1=[O:13])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 24758Sodium hydride2×HCID 58359251(R)-N-Benzyl-2-chloro-N-(2-(6-(4-fluorophenyl)-4,5-dimethylpyridazin-3-ylamino)ethyl)propanamide

Product 1

HCID 583592571-Benzyl-4-(6-(4-fluorophenyl)-4,5-dimethylpyridazin-3-yl)-3-methylpiperazin-2-oneYield 86.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Treat a 0° C. solution of (R)—N-benzyl-2-chloro-N-(2-(6-(4-fluorophenyl)-4,5-dimethylpyridazin-3-ylamino)ethyl)propanamide (4.59 g, 10.4 mmol) in THF (104 mL) with NaH (60%, 625 mg, 15.6 mmol). Allow the reaction mixture to warm to ambient temperature and stir overnight. Cool the reaction to 0° C., and treat with additional NaH (60%, 208 mg, 5.20 mmol). Allow the reaction mixture to warm to ambient temperature and stir for 3 d. Partition the reaction mixture between brine and EtOAc. Separate the organic layer, dry over Na2SO4, filter, and concentrate under reduced pressure. Purify the residue by flash silica gel chromatography (gradient of 0 to 2% 2 M NH3/MeOH in CH2Cl2) to provide the title compound as a white foam (3.64 g, 86%). ES/MS m/z 405.2 (M+1).

Workup

  1. temperatureCool
  2. customthe reaction to 0° C.
  3. temperatureto warm to ambient temperature
  4. stirringstir for 3 d
  5. customPartition the reaction mixture between brine and EtOAc
  6. customSeparate the organic layer
  7. dry with materialdry over Na2SO4
  8. filtrationfilter
  9. concentrationconcentrate under reduced pressure
  10. customPurify the residue by flash silica gel chromatography (gradient of 0 to 2% 2 M NH3/MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-5791c2891401438f83a6e87e3abd7e8f
Source dataset
uspto-grants-2013_05
Patent number
US08445493B2

Reaction notes

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