1,8-Diazabicyclo(5.4.0)undec-7-ene → 4'-{[4-(1,4-Dioxaspiro[4.5]dec-8-yl)-5-oxo-7-propyl-2-(trifluoromethyl)-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl]methyl}biphenyl-2-carbonitrile

HRID 1688744Notes

Reaction equation

HRID 1688744 reaction equation
[O:1]1[C:5]2([CH2:10][CH2:9][CH:8]([NH:11][C:12]3[N:16]=[C:15]([C:17]([F:20])([F:19])[F:18])[NH:14][N:13]=3)[CH2:7][CH2:6]2)[O:4][CH2:3][CH2:2]1.[C:21]([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=1[C:29]1[CH:34]=[CH:33][C:32]([CH2:35][CH:36]([C:42](=O)[CH2:43][CH2:44][CH3:45])[C:37](OCC)=[O:38])=[CH:31][CH:30]=1)#[N:22].N12CCCN=C1CCCCC2>C(N(CC)C1C=CC=CC=1)C.C(OCC)(=O)C>[O:1]1[C:5]2([CH2:10][CH2:9][CH:8]([N:11]3[C:37](=[O:38])[C:36]([CH2:35][C:32]4[CH:33]=[CH:34][C:29]([C:24]5[C:23]([C:21]#[N:22])=[CH:28][CH:27]=[CH:26][CH:25]=5)=[CH:30][CH:31]=4)=[C:42]([CH2:43][CH2:44][CH3:45])[N:13]4[N:14]=[C:15]([C:17]([F:20])([F:18])[F:19])[N:16]=[C:12]34)[CH2:7][CH2:6]2)[O:4][CH2:3][CH2:2]1

Participants

6

Reactant 3

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 10020734Ethyl 2-[(2'-cyanobiphenyl-4-yl)methyl]-3-oxohexanoateHCID 67008537N-(1,4-dioxaspiro[4.5]dec-8-yl)-5-(trifluoromethyl)-1H-1,2,4-triazol-3-amine

Product 1

HCID 670096644'-{[4-(1,4-Dioxaspiro[4.5]dec-8-yl)-5-oxo-7-propyl-2-(trifluoromethyl)-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl]methyl}biphenyl-2-carbonitrileYield 41%

Reagents, catalysts & solvents 2

HCID 7061N,N-DiethylanilineSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of N-(1,4-dioxaspiro[4.5]dec-8-yl)-5-(trifluoromethyl)-1H-1,2,4-triazol-3-amine (9.87 g), ethyl 2-[(2′-cyanobiphenyl-4-yl)methyl]-3-oxohexanoate (23.59 g) and 1,8-diazabicyclo[5.4.0]undec-7-ene (5.05 mL) in N,N-diethylaniline (50 mL) was stirred at 180° C. for 16 hr. The reaction mixture was diluted with ethyl acetate, and the mixture was washed with 1 N hydrochloric acid and then with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel chromatography [eluent: hexane/ethyl acetate=80/20→60/40 (volume ratio)], and crystallized from diisopropyl ether to give the title compound as a colorless solid (7.91 g, 41%).

Workup

  1. washthe mixture was washed with 1 N hydrochloric acid
  2. dry with materialwith saturated brine, and dried over anhydrous magnesium sulfate
  3. customThe solvent was evaporated under reduced pressure
  4. customthe residue was purified by silica gel chromatography [eluent: hexane/ethyl acetate=80/20→60/40 (volume ratio)]
  5. customcrystallized from diisopropyl ether

Sources & evidence

ORD record
ord-1f2d39f4790f47d2b912c41a82afe8be
Source dataset
uspto-grants-2012_04
Patent number
US08148383B2

Reaction notes

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