Methanol → 3-(3-Benzoyl-3-azabicyclo[3.1.0]hexane-6-carboxamido)methyl-5-isobutyl-1-phenyl-1H-pyrazole

HRID 340749Notes

Reaction equation

HRID 340749 reaction equation
Cl.[CH2:2]([C:6]1[N:10]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[N:9]=[C:8]([CH2:17][NH:18][C:19]([CH:21]2[CH:26]3[CH:22]2[CH2:23][NH:24][CH2:25]3)=[O:20])[CH:7]=1)[CH:3]([CH3:5])[CH3:4].C(N(CC)CC)C.[C:34](Cl)(=[O:41])[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1.CO>C(Cl)Cl>[C:34]([N:24]1[CH2:25][CH:26]2[CH:22]([CH:21]2[C:19]([NH:18][CH2:17][C:8]2[CH:7]=[C:6]([CH2:2][CH:3]([CH3:5])[CH3:4])[N:10]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)[N:9]=2)=[O:20])[CH2:23]1)(=[O:41])[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 7412Benzoyl chlorideHCID 8471TriethylamineHCID 1177004486-((5-Isobutyl-1-phenyl-1H-pyrazole-3-yl)methylcarbamoyl)-3-azabicyclo[3.1.0]hexane hydrochloride

Product 1

HCID 862929383-(3-Benzoyl-3-azabicyclo[3.1.0]hexane-6-carboxamido)methyl-5-isobutyl-1-phenyl-1H-pyrazoleYield 83.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

The 6-((5-isobutyl-1-phenyl-1H-pyrazole-3-yl)methylcarbamoyl)-3-azabicyclo[3.1.0]hexane hydrochloride (367 mg, 0.979 mmol) prepared in Example 11 was dissolved in 4.9 mL of methylene chloride and triethylamine (273 μL, 1.96 mmol) was added dropwise at 0° C. After stirring for 5 minutes, benzoyl chloride (125 μL, 1.08 mmol) was added dropwise. 10 minutes later, after stirring at room temperature for 3 hours, the completion of the reaction was confirmed by TLC (CH2Cl2:MeOH=20:1). After the reaction was completed, the reaction mixture was extracted with methylene chloride after adding water, 1 N HCl and saturated sodium bicarbonate. The organic layer was dried with anhydrous magnesium sulfate, filtered, concentrated under reduced pressure and separated by column chromatography (CH2Cl2:MeOH=20:1) to obtain 360 mg (83.2%) of the target compound.

Workup

  1. stirring10 minutes later, after stirring at room temperature for 3 hours
  2. extractionthe reaction mixture was extracted with methylene chloride
  3. additionafter adding water, 1 N HCl and saturated sodium bicarbonate
  4. dry with materialThe organic layer was dried with anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customseparated by column chromatography (CH2Cl2:MeOH=20:1)

Sources & evidence

ORD record
ord-2ef29c51c5e84cfca3d73db5f1f1a77e
Source dataset
uspto-grants-2014_11
Patent number
US08895602B1

Reaction notes

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