Hydrochloric Acid → 3-(4-Benzyl-2-methylpiperazin-1-yl)-6-(4-fluorophenyl)-4,5-dimethylpyridazine

HRID 2093365Notes

Reaction equation

HRID 2093365 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[N:15]=[N:16][C:17]([C:22]3[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=3)=[C:18]([CH3:21])[C:19]=2[CH3:20])[CH:10]([CH3:29])[C:9]1=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CO.Cl>C1COCC1.O1CCOCC1>[CH2:1]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[N:15]=[N:16][C:17]([C:22]3[CH:23]=[CH:24][C:25]([F:28])=[CH:26][CH:27]=3)=[C:18]([CH3:21])[C:19]=2[CH3:20])[CH:10]([CH3:29])[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 887MethanolHCID 583592571-Benzyl-4-(6-(4-fluorophenyl)-4,5-dimethylpyridazin-3-yl)-3-methylpiperazin-2-one

Product 1

HCID 583592493-(4-Benzyl-2-methylpiperazin-1-yl)-6-(4-fluorophenyl)-4,5-dimethylpyridazine

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
50 °C

Procedure

Treat a solution of 1-benzyl-4-(6-(4-fluorophenyl)-4,5-dimethylpyridazin-3-yl)-3-methylpiperazin-2-one (2.84 g, 7.02 mmol) in THF (70 mL) with borane-methyl sulfide complex (1.96 mL, 21.1 mmol). Heat the resulting mixture at 50° C. for 2 h. Cool the reaction mixture in an ice bath, add MeOH (20 mL) via a dropping funnel followed by 4 M HCl in 1,4-dioxane (20 mL). Heat the resulting mixture at 65° C. for 1 h. Concentrate the mixture under reduced pressure. Partition the residue between CH2Cl2 and saturated NaHCO3 (aq). Separate the layers, and extract the aqueous layer with CH2Cl2. Combine the organic layers, dry over Na2SO4, filter, and concentrate under reduced pressure. Purify the residue by flash silica gel chromatography (gradient of 0 to 3% 2 M NH3/MeOH in CH2Cl2) to afford the title compound as a waxy solid (2.45 g, 89%). ES/MS m/z 391.2 (M+1).

Workup

  1. temperatureCool the reaction mixture in an ice bath
  2. temperatureHeat the resulting mixture at 65° C. for 1 h
  3. concentrationConcentrate the mixture under reduced pressure
  4. customPartition the residue between CH2Cl2 and saturated NaHCO3 (aq)
  5. customSeparate the layers
  6. extractionextract the aqueous layer with CH2Cl2
  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 3% 2 M NH3/MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-4a51965c934f4e61a13d58129d79af43
Source dataset
uspto-grants-2013_05
Patent number
US08445493B2

Reaction notes

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