Dichloromethane → tert-Butyl 6((5-isobutyl-1-phenyl-1H-pyrazole-3-yl)methylcarbamoyl)-3-azabicyclo[3.1.0]hexane-3-carboxylate

HRID 340746Notes

Reaction equation

HRID 340746 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH:12]2[CH:10]([CH:11]2[C:14]([OH:16])=O)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].O[C:18]1[C:26]2[N:25]=[N:24]N[C:22]=2[CH:21]=[CH:20][CH:19]=1.C(N=C=N[CH2:32][CH2:33][CH2:34][N:35](C)C)C.CC[CH2:40][CH2:41][CH2:42][CH3:43].[CH2:44](Cl)Cl>C(OCC)(=O)C>[CH2:42]([C:43]1[N:25]([C:26]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)[N:24]=[C:33]([CH2:34][NH:35][C:14]([CH:11]2[CH:10]3[CH:12]2[CH2:13][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:9]3)=[O:16])[CH:32]=1)[CH:41]([CH3:44])[CH3:40]

Participants

7

Reactant 5

HCID 6344DichloromethaneHCID 8058HexaneHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 533952883-((Tert-butoxy)carbonyl)-3-azabicyclo(3.1.0)hexane-6-carboxylic acidHCID 178418300HCID 178418300, compound

Product 1

HCID 117700883tert-Butyl 6((5-isobutyl-1-phenyl-1H-pyrazole-3-yl)methylcarbamoyl)-3-azabicyclo[3.1.0]hexane-3-carboxylateYield 92.1%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

The 3-(tert-butoxycarbonyl)-3-azabicyclo[3.1.0]hexane-6-carboxylic acid (185 mg, 0.812 mmol) prepared in Example 3, hydroxybenzotriazole (132 mg, 0.975 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (187 mg, 0.975 mmol) were dissolved in 3.0 mL of methylene chloride and the (5-isobutyl-3-aminomethyl-1-phenyl)pyrazole (205 mg, 0.894 mmol) prepared in Example 9 was added dropwise. After stirring for 3 hours, the completion of the reaction was confirmed by TLC (hexane:ethyl acetate=1:2). After the reaction was completed, the mixture was extracted with methylene chloride after adding water and saturated sodium bicarbonate. The organic layer was dried with anhydrous sodium sulfate, filtered, concentrated under reduced pressure and separated by column chromatography (hexane:ethyl acetate=1:2) to obtain 328 mg (92.1%) of the target compound.

Workup

  1. extractionthe mixture was extracted with methylene chloride
  2. additionafter adding water and saturated sodium bicarbonate
  3. dry with materialThe organic layer was dried with anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customseparated by column chromatography (hexane:ethyl acetate=1:2)

Sources & evidence

ORD record
ord-3b639d774e9a4c0ab245e24bc1f84534
Source dataset
uspto-grants-2014_11
Patent number
US08895602B1

Reaction notes

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