N,N-Diethylaniline → 4'-{[7-Butyl-4-(1,4-dioxaspiro[4.5]dec-8-yl)-5-oxo-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl]methyl}-3'-fluorobiphenyl-2-carbonitrile

HRID 1688848Notes

Reaction equation

HRID 1688848 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[CH:14]=[CH:13][C:12]([CH2:15][CH:16]([C:21](=O)[CH2:22][CH2:23][CH2:24][CH3:25])[C:17](OC)=[O:18])=[C:11]([F:27])[CH:10]=1)#[N:2].[O:28]1[C:32]2([CH2:37][CH2:36][CH:35]([NH:38][C:39]3[NH:43][CH:42]=[N:41][N:40]=3)[CH2:34][CH2:33]2)[O:31][CH2:30][CH2:29]1.N12CCCN=C1CCCCC2.C(N(CC)C1C=CC=CC=1)C>Cl>[CH2:22]([C:21]1[N:40]2[N:41]=[CH:42][N:43]=[C:39]2[N:38]([CH:35]2[CH2:34][CH2:33][C:32]3([O:28][CH2:29][CH2:30][O:31]3)[CH2:37][CH2:36]2)[C:17](=[O:18])[C:16]=1[CH2:15][C:12]1[CH:13]=[CH:14][C:9]([C:4]2[C:3]([C:1]#[N:2])=[CH:8][CH:7]=[CH:6][CH:5]=2)=[CH:10][C:11]=1[F:27])[CH2:23][CH2:24][CH3:25]

Participants

6

Reactant 4

HCID 7061N,N-DiethylanilineHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 57460325Methyl 2-[(2'-cyano-3-fluorobiphenyl-4-yl)methyl]-3-oxoheptanoateHCID 178420920N-(1,4-dioxaspiro[4.5]dec-8-yl)-4H-1,2,4-triazol-3-amine

Product 1

HCID 670091284'-{[7-Butyl-4-(1,4-dioxaspiro[4.5]dec-8-yl)-5-oxo-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl]methyl}-3'-fluorobiphenyl-2-carbonitrileYield 60%

Reagents, catalysts & solvents 1

HCID 313Hydrochloric AcidSolvent

Conditions

Temperature
180 °C

Procedure

A mixture of methyl 2-[(2′-cyano-3-fluorobiphenyl-4-yl)methyl]-3-oxoheptanoate (6.55 g), N-(1,4-dioxaspiro[4.5]dec-8-yl)-4H-1,2,4-triazol-3-amine (2.00 g), 1,8-diazabicyclo[5.4.0]undec-7-ene (0.5 mL) and N,N-diethylaniline (20 mL) was stirred at 180° C. overnight, allowed to cool, and poured into 1 M hydrochloric acid (100 mL), and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography to give the title compound as a pale-yellow oil (2.88 g, 60%).

Workup

  1. temperatureto cool
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe ethyl acetate layer was washed with saturated brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customThe solvent was evaporated under reduced pressure
  6. customthe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-599bf03e407e490295cb02d5cf5e3c7c
Source dataset
uspto-grants-2012_04
Patent number
US08148383B2

Reaction notes

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