Triethylamine → 3-[3-(3,3-Dimethylbutyl)-3-azabicyclo[3.1.0]hexane-6-carboxamido]methyl-5-isobutyl-1-phenyl-1H-pyrazole

HRID 340748Notes

Reaction equation

HRID 340748 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.[CH3:34][C:35]([CH3:40])([CH3:39])[CH2:36][CH:37]=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl.C(OCC)(=O)C.CCCCCC>[CH3:34][C:35]([CH3:40])([CH3:39])[CH2:36][CH2:37][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

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 763353,3-DimethylbutanalHCID 5049666Sodium triacetoxyborohydrideHCID 1177004486-((5-Isobutyl-1-phenyl-1H-pyrazole-3-yl)methylcarbamoyl)-3-azabicyclo[3.1.0]hexane hydrochloride

Product 1

HCID 862927533-[3-(3,3-Dimethylbutyl)-3-azabicyclo[3.1.0]hexane-6-carboxamido]methyl-5-isobutyl-1-phenyl-1H-pyrazoleYield 64%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolvent2×HCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

The 6-((5-isobutyl-1-phenyl-1H-pyrazole-3-yl)methylcarbamoyl)-3-azabicyclo[3.1.0]hexane hydrochloride (93.5 mg, 0.249 mmol) prepared in Example 11 and a molecular sieve were dried in vacuum and dissolved in 2 mL of methylene chloride. Then, triethylamine (35 μL, 0.249 mmol) was added dropwise at 0° C. After adding 3,3-dimethylbutyraldehyde (31 μL, 0.249 mmol) dropwise, the mixture was stirred at room temperature for 1 hour. After adding sodium triacetoxyborohydride (159 mg, 0.748 mmol), the mixture was stirred for 2 hours and 30 minutes. The completion of the reaction was confirmed by TLC (hexane:ethyl acetate=1:2). After the reaction was completed, the reaction mixture was diluted with methylene chloride and extracted several times with saturated sodium bicarbonate. The organic layer was dried with anhydrous magnesium sulfate, filtered, concentrated under reduced pressure and separated by column chromatography (CH2Cl2:MeOH=15:1) to obtain 67.3 mg (63.9%) of the target compound.

Workup

  1. stirringthe mixture was stirred for 2 hours and 30 minutes
  2. extractionextracted several times with saturated sodium bicarbonate
  3. dry with materialThe organic layer was dried with anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customseparated by column chromatography (CH2Cl2:MeOH=15:1)

Sources & evidence

ORD record
ord-76cfff66caa34274871a17f430d00ae5
Source dataset
uspto-grants-2014_11
Patent number
US08895602B1

Reaction notes

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