Toluene → 1,1-Dimethylethyl 2-[4-(3-methyl-1,2,4-oxadiazol-5-yl)phenyl]-4,5,7,8-tetrahydropyrazolo[3,4-d]azepine-6(2H)-carboxylate

HRID 1364125Notes

Reaction equation

HRID 1364125 reaction equation
[CH3:1][C:2]([O:5][C:6]([N:8]1[CH2:14][CH2:13][C:12]2=[CH:15][N:16]([C:18]3[CH:26]=[CH:25][C:21]([C:22]([OH:24])=O)=[CH:20][CH:19]=3)[N:17]=[C:11]2[CH2:10][CH2:9]1)=[O:7])([CH3:4])[CH3:3].O=C(N1C=CN=C1)N1C=CN=C1.C1(C)C=CC=CC=1.O[NH:47]/[C:48](=[N:50]\[H])/[CH3:49]>ClCCl>[CH3:49][C:48]1[N:50]=[C:22]([C:21]2[CH:20]=[CH:19][C:18]([N:16]3[CH:15]=[C:12]4[C:11]([CH2:10][CH2:9][N:8]([C:6]([O:5][C:2]([CH3:3])([CH3:4])[CH3:1])=[O:7])[CH2:14][CH2:13]4)=[N:17]3)=[CH:26][CH:25]=2)[O:24][N:47]=1

Participants

6

Reactant 4

HCID 1140TolueneHCID 682631,1'-Carbonyldiimidazole2×HCID 669308134-[6-{[(1,1-dimethylethyl)oxy]carbonyl}-5,6,7,8-tetrahydropyrazolo[3,4-d]azepin-2(4H)-yl]benzoic acidHCID 178506480HCID 178506480, compound2×

Product 1

HCID 669308431,1-Dimethylethyl 2-[4-(3-methyl-1,2,4-oxadiazol-5-yl)phenyl]-4,5,7,8-tetrahydropyrazolo[3,4-d]azepine-6(2H)-carboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a suspension of 4-[6-{[(1,1-dimethylethyl)oxy]carbonyl}-5,6,7,8-tetrahydropyrazolo[3,4-d]azepin-2(4H)-yl]benzoic acid (may be prepared as described in Description 23) (185 mg, 0.52 mmol) in dichloromethane (10 ml) was added 1,1′-(oxomethanediyl)bis-1H-imidazole (168 mg, 1.04 mmol) and the reaction stirred at room temperature, under argon, overnight. The solvent was evaporated in vacuo. Toluene (5 ml) and then (1Z)-N-hydroxyethanimidamide (may be prepared as described in Description 30) (116 mg, 1.56 mmol) were added and the reaction mixture heated, under argon, at reflux overnight. A further 2 eq. of 1,1′-(oxomethanediyl)bis-1H-imidazole was added and stirring continued for a further 40 minutes. A further 3 eq. of (1Z)-N-hydroxyethanimidamide was added and stirring continued for a further 3 hours. The reaction was cooled to room temperature and the solvent evaporated in vacuo. The resulting crude mixture was diluted with dichloromethane and water, and extracted into dichloromethane (×2). The combined organic fractions were washed with water (×1), dried over magnesium sulphate and solvent evaporated in vacuo to afford the title compound (D34). MS (ES+) m/e 340 [M-tBu]+.

Workup

  1. customThe solvent was evaporated in vacuo
  2. temperaturethe reaction mixture heated, under argon
  3. temperatureat reflux overnight
  4. stirringstirring
  5. waitcontinued for a further 40 minutes
  6. stirringstirring
  7. waitcontinued for a further 3 hours
  8. temperatureThe reaction was cooled to room temperature
  9. customthe solvent evaporated in vacuo
  10. additionThe resulting crude mixture was diluted with dichloromethane and water
  11. extractionextracted into dichloromethane (×2)
  12. washThe combined organic fractions were washed with water (×1)
  13. dry with materialdried over magnesium sulphate and solvent
  14. customevaporated in vacuo

Sources & evidence

ORD record
ord-cae10ccc409a4588b334cd867f291f57
Source dataset
uspto-grants-2011_02
Patent number
US07888347B2

Reaction notes

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