Triethylamine → 4-{[(4-fluoro-7-methoxy-2,3-dihydrobenzofuran-5-yl)-(5-oxo-1-pyrimidin-2-yl-4,5-dihydro-1H-[1,2,4]triazol-3-yl)methyl]amino}benzonitrile

HRID 1161513Notes

Reaction equation

HRID 1161513 reaction equation
[NH:1]([C:3]1[N:8]=[CH:7][CH:6]=[CH:5][N:4]=1)[NH2:2].C(N(CC)CC)C.C[O:17][C:18](=O)[N:19]=[C:20](SC)[C:21](=[N:34][C:35]1[CH:40]=[CH:39][C:38]([C:41]#[N:42])=[CH:37][CH:36]=1)[C:22]1[CH:23]=[C:24]([O:32][CH3:33])[C:25]2[O:29][CH2:28][CH2:27][C:26]=2[C:30]=1[F:31]>CN(C=O)C>[F:31][C:30]1[C:26]2[CH2:27][CH2:28][O:29][C:25]=2[C:24]([O:32][CH3:33])=[CH:23][C:22]=1[CH:21]([NH:34][C:35]1[CH:36]=[CH:37][C:38]([C:41]#[N:42])=[CH:39][CH:40]=1)[C:20]1[NH:19][C:18](=[O:17])[N:1]([C:3]2[N:8]=[CH:7][CH:6]=[CH:5][N:4]=2)[N:2]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 3465582-HydrazinylpyrimidineHCID 72312842[2-(4-Cyanophenylimino)-2-(4-fluoro-7-methoxy-2,3-dihydrobenzofuran-5-yl)-1-methylsulfanylethylidene]carbamic acid methyl ester

Product 1

HCID 1363892714-{[(4-fluoro-7-methoxy-2,3-dihydrobenzofuran-5-yl)-(5-oxo-1-pyrimidin-2-yl-4,5-dihydro-1H-[1,2,4]triazol-3-yl)methyl]amino}benzonitrileYield 68.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
85 °C

Procedure

After adding 144 mg of 2-hydrazinopyrimidine and 900 μl of triethylamine to a solution of 624 mg of [2-(4-cyanophenylimino)-2-(4-fluoro-7-methoxy-2,3-dihydrobenzofuran-5-yl)-1-methylsulfanylethylidene]carbamic acid methyl ester in 12 ml of DMF, the mixture was stirred overnight at 85° C. under a nitrogen atmosphere. The reaction mixture was concentrated, and the residue was dissolved in 6.6 ml of a methanol:acetic acid=10:1 mixed solvent. After adding 1 g of sodium cyanotrihydroborate to the solution, the mixture was stirred at room temperature for 1 hour. Ethyl acetate was added to the reaction mixture. The organic layer was washed with dilute hydrochloric acid and saturated brine and then dried over anhydrous magnesium sulfate. The desiccating agent was filtered off and the filtrate was concentrated under reduced pressure. The residue was purified by NAM silica gel column chromatography (methanol-ethyl acetate) to give 4-{[(4-fluoro-7-methoxy-2,3-dihydrobenzofuran-5-yl)-(5-oxo-1-pyrimidin-2-yl-4,5-dihydro-1H-[1,2,4]triazol-3-yl)methyl]amino}benzonitrile (414 mg) as a light yellow solid.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. dissolutionthe residue was dissolved in 6.6 ml of a methanol
  3. additionAfter adding 1 g of sodium cyanotrihydroborate to the solution
  4. stirringthe mixture was stirred at room temperature for 1 hour
  5. additionEthyl acetate was added to the reaction mixture
  6. washThe organic layer was washed with dilute hydrochloric acid and saturated brine
  7. dry with materialdried over anhydrous magnesium sulfate
  8. filtrationThe desiccating agent was filtered off
  9. concentrationthe filtrate was concentrated under reduced pressure
  10. customThe residue was purified by NAM silica gel column chromatography (methanol-ethyl acetate)

Sources & evidence

ORD record
ord-d0c142ed01ee4f5695052dacdbea08f3
Source dataset
uspto-grants-2010_10
Patent number
US07816522B2

Reaction notes

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