Triethyl phosphonoacetate → ethyl (4-{6-[(2'-cyanobiphenyl-4-yl)methyl]-5-oxo-7-propyl[1,2,4]triazolo[1,5-a]pyrimidin-4(5H)-yl}cyclohexylidene)acetate

HRID 1412289Notes

Reaction equation

HRID 1412289 reaction equation
[CH2:1]([O:3][C:4](=[O:14])[CH2:5]P(OCC)(OCC)=O)[CH3:2].[H-].[Na+].[O:17]=[C:18]1[C:23]([CH2:24][C:25]2[CH:30]=[CH:29][C:28]([C:31]3[C:32]([C:37]#[N:38])=[CH:33][CH:34]=[CH:35][CH:36]=3)=[CH:27][CH:26]=2)=[C:22]([CH2:39][CH2:40][CH3:41])[N:21]2[N:42]=[CH:43][N:44]=[C:20]2[N:19]1[CH:45]1[CH2:50][CH2:49][C:48](=O)[CH2:47][CH2:46]1>O1CCCC1>[CH2:1]([O:3][C:4](=[O:14])[CH:5]=[C:48]1[CH2:47][CH2:46][CH:45]([N:19]2[C:18](=[O:17])[C:23]([CH2:24][C:25]3[CH:30]=[CH:29][C:28]([C:31]4[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=4[C:37]#[N:38])=[CH:27][CH:26]=3)=[C:22]([CH2:39][CH2:40][CH3:41])[N:21]3[N:42]=[CH:43][N:44]=[C:20]23)[CH2:50][CH2:49]1)[CH3:2]

Participants

5

Reactant 3

HCID 13345Triethyl phosphonoacetateHCID 24758Sodium hydrideHCID 670088534'-{[5-Oxo-4-(4-oxocyclohexyl)-7-propyl-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl]methyl}biphenyl-2-carbonitrile

Product 1

HCID 86644029ethyl (4-{6-[(2'-cyanobiphenyl-4-yl)methyl]-5-oxo-7-propyl[1,2,4]triazolo[1,5-a]pyrimidin-4(5H)-yl}cyclohexylidene)acetateYield 86%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution (10 mL) of ethyl(diethoxyphosphoryl)acetate (1.2 g) in tetrahydrofuran was added sodium hydride (0.21 g), and the mixture was stirred at room temperature for 1 hr. A solution (10 mL) of 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 (2 g) in tetrahydrofuran was added to the reaction mixture, and the mixture was stirred at room temperature for 3 hr. The reaction mixture was extracted with 1 N hydrochloric acid and ethyl acetate, and the obtained 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 colorless solid (1.9 g, 86%). 1H NMR (300 MHz, CHLOROFORM-d) δ1.06 (t, J=7.4 Hz, 3H), 1.28 (t, J=7.2 Hz, 3H), 1.66-1.80 (m, 2H), 1.87-1.98 (m, 2H), 1.99-2.12 (m, 2H), 2.33-2.51 (m, 2H), 2.65-2.89 (m, 2H), 2.98-3.08 (m, 2H), 4.02 (s, 2H), 4.07-4.19 (m, 2H), 5.23-5.38 (m, 1H), 5.71 (s, 1H), 7.35-7.52 (m, 6H), 7.58-7.67 (m, 1H), 7.75 (d, J=7.6 Hz, 1H), 7.90 (s, 1H)

Workup

  1. stirringthe mixture was stirred at room temperature for 3 hr
  2. extractionThe reaction mixture was extracted with 1 N hydrochloric acid and ethyl acetate
  3. washthe obtained 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-88a24f0822964c8ca6fd01d311ef3e4b
Source dataset
uspto-grants-2014_12
Patent number
US08921379B2

Reaction notes

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