Acetone → 6-(1-Methylethyl)-2-[4-(3-methyl-1,2,4-oxadiazol-5-yl)phenyl]-2,4,5,6,7,8-hexahydropyrazolo[3,4-d]azepine

HRID 1364145Notes

Reaction equation

HRID 1364145 reaction equation
[CH3:1][C:2]1[N:6]=[C:5]([C:7]2[CH:12]=[CH:11][C:10]([N:13]3[CH:22]=[C:21]4[C:15]([CH2:16][CH2:17][NH:18][CH2:19][CH2:20]4)=[N:14]3)=[CH:9][CH:8]=2)[O:4][N:3]=1.[CH3:23][C:24]([CH3:26])=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl.C(O)(=O)C.CO>[CH3:23][CH:24]([N:18]1[CH2:19][CH2:20][C:21]2=[CH:22][N:13]([C:10]3[CH:11]=[CH:12][C:7]([C:5]4[O:4][N:3]=[C:2]([CH3:1])[N:6]=4)=[CH:8][CH:9]=3)[N:14]=[C:15]2[CH2:16][CH2:17]1)[CH3:26]

Participants

7

Reactant 3

HCID 180AcetoneHCID 5049666Sodium triacetoxyborohydrideHCID 669307922-[4-(3-Methyl-1,2,4-oxadiazol-5-yl)phenyl]-2,4,5,6,7,8-hexahydropyrazolo[3,4-d]azepine

Product 1

HCID 160487586-(1-Methylethyl)-2-[4-(3-methyl-1,2,4-oxadiazol-5-yl)phenyl]-2,4,5,6,7,8-hexahydropyrazolo[3,4-d]azepine

Reagents, catalysts & solvents 3

HCID 176Acetic AcidCatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-[4-(3-methyl-1,2,4-oxadiazol-5-yl)phenyl]-2,4,5,6,7,8-hexahydropyrazolo[3,4-d]azepine (may be prepared as described in Description 35) (31 mg, 0.10 mmol) in dichloromethane (4 ml) was added acetone (24 mg, 0.42 mmol) and acetic acid (3 drops). The resulting mixture was stirred at room temperature, under argon, for 20 minutes. Sodium triacetoxyborohydride (89 mg, 0.42 mmol) was added and stirring continued overnight. The resulting crude mixture was diluted with methanol and then purified by SCX, eluting with methanol and then with 2M ammonia/methanol. The basic fractions were combined and solvent evaporated in vacuo. Crude product was purified further by column chromatography on silica gel, eluting with a mixture of 2M ammonia in methanol/dichloromethane (0-1%). Resulting crude product was purified further by column chromatography on silica gel, eluting with a mixture of 2M ammonia in methanol/dichloromethane (0-1%) to afford the title compound (E15). MS (ES+) m/e 338 [M+H]+.

Workup

  1. stirringstirring continued overnight
  2. custompurified by SCX
  3. washeluting with methanol
  4. customsolvent evaporated in vacuo
  5. customCrude product was purified further by column chromatography on silica gel
  6. washeluting with a mixture of 2M ammonia in methanol/dichloromethane (0-1%)
  7. customResulting crude product
  8. customwas purified further by column chromatography on silica gel
  9. washeluting with a mixture of 2M ammonia in methanol/dichloromethane (0-1%)

Sources & evidence

ORD record
ord-28ce01207fbc46c5a5d771f5236a7b5b
Source dataset
uspto-grants-2011_02
Patent number
US07888347B2

Reaction notes

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