Methanol → 3'-Fluoro-4'-{[5-oxo-4-(4-oxocyclohexyl)-7-propyl-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl]methyl}biphenyl-2-carbonitrile

HRID 1688590Notes

Reaction equation

HRID 1688590 reaction equation
O1[C:5]2([CH2:10][CH2:9][CH:8]([N:11]3[C:16](=[O:17])[C:15]([CH2:18][C:19]4[CH:24]=[CH:23][C:22]([C:25]5[C:26]([C:31]#[N:32])=[CH:27][CH:28]=[CH:29][CH:30]=5)=[CH:21][C:20]=4[F:33])=[C:14]([CH2:34][CH2:35][CH3:36])[N:13]4[N:37]=[CH:38][N:39]=[C:12]34)[CH2:7][CH2:6]2)[O:4]CC1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.CO.O1CCCC1>C(OCC)(=O)C>[F:33][C:20]1[CH:21]=[C:22]([C:25]2[C:26]([C:31]#[N:32])=[CH:27][CH:28]=[CH:29][CH:30]=2)[CH:23]=[CH:24][C:19]=1[CH2:18][C:15]1[C:16](=[O:17])[N:11]([CH:8]2[CH2:7][CH2:6][C:5](=[O:4])[CH2:10][CH2:9]2)[C:12]2[N:13]([N:37]=[CH:38][N:39]=2)[C:14]=1[CH2:34][CH2:35][CH3:36]

Participants

6

Reactant 4

HCID 887MethanolHCID 8028TetrahydrofuranHCID 521998p-Toluenesulfonic acid monohydrateHCID 670090304'-{[4-(1,4-Dioxaspiro[4.5]dec-8-yl)-5-oxo-7-propyl-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl]methyl}-3'-fluorobiphenyl-2-carbonitrile

Product 1

HCID 670088843'-Fluoro-4'-{[5-oxo-4-(4-oxocyclohexyl)-7-propyl-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl]methyl}biphenyl-2-carbonitrileYield 76%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of 4′-{[4-(1,4-dioxaspiro[4.5]dec-8-yl)-5-oxo-7-propyl-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl]methyl}-3′-fluorobiphenyl-2-carbonitrile (3.1 g), p-toluenesulfonic acid monohydrate (0.1 g), methanol (50 mL) and tetrahydrofuran (50 mL) was stirred at 60° C. for 16 hr. The reaction mixture was diluted with ethyl acetate, washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was dissolved in acetone (20 mL), 1 N hydrochloric acid (20 mL) was added, and the mixture was stirred at room temperature for 2 hr. The reaction mixture was diluted with ethyl acetate, 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 colorless solid (2.1 g, 76%).

Workup

  1. washwashed with saturated brine
  2. dry with materialdried over anhydrous magnesium sulfate
  3. customThe solvent was evaporated under reduced pressure
  4. dissolutionThe obtained residue was dissolved in acetone (20 mL)
  5. addition1 N hydrochloric acid (20 mL) was added
  6. stirringthe mixture was stirred at room temperature for 2 hr
  7. additionThe reaction mixture was diluted with ethyl acetate
  8. washwashed with saturated brine
  9. dry with materialdried over anhydrous magnesium sulfate
  10. customThe solvent was evaporated under reduced pressure
  11. customthe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-ba9cd39e8cd64f288708b62c355be2a4
Source dataset
uspto-grants-2012_04
Patent number
US08148383B2

Reaction notes

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