Dimethylformamide → 4-{6-[(3,3-dimethyl-2,3-dihydro-1-benzofuran-4-yl)oxy]pyridin-3-yl}-5-methyl-2,4-dihydro-3H-1,2,4-triazol-3-one

HRID 1484519Notes

Reaction equation

HRID 1484519 reaction equation
[CH3:1][C:2]1([CH3:12])[C:6]2=[C:7]([OH:11])[CH:8]=[CH:9][CH:10]=[C:5]2[O:4][CH2:3]1.CN(C=O)C.F[C:19]1[N:24]=[CH:23][C:22]([N:25]2[C:29](=[O:30])[NH:28][N:27]=[C:26]2[CH3:31])=[CH:21][CH:20]=1>>[CH3:1][C:2]1([CH3:12])[C:6]2[C:7]([O:11][C:19]3[N:24]=[CH:23][C:22]([N:25]4[C:26]([CH3:31])=[N:27][NH:28][C:29]4=[O:30])=[CH:21][CH:20]=3)=[CH:8][CH:9]=[CH:10][C:5]=2[O:4][CH2:3]1

Participants

4

Reactant 3

HCID 6228DimethylformamideHCID 574112993,3-Dimethyl-2,3-dihydro-1-benzofuran-4-ol2×HCID 727043314-(6-fluoro-3-pyridyl)-3-methyl-1H-1,2,4-triazol-5-one2×

Product 1

HCID 727037204-{6-[(3,3-dimethyl-2,3-dihydro-1-benzofuran-4-yl)oxy]pyridin-3-yl}-5-methyl-2,4-dihydro-3H-1,2,4-triazol-3-oneYield 27.7%

Conditions

Temperature
110 °C

Procedure

To a solution of 3,3-dimethyl-2H-benzofuran-4-ol (WO2012/076877 Intermediate 50, 30 mg, 0.18 mmol) in dry DMF (0.5 mL) dipotassium carbonate (50.5 mg, 0.36 mmol) and then 4-(6-fluoro-3-pyridyl)-3-methyl-1H-1,2,4-triazol-5-one (Intermediate 8, 24.8 mg, 0.128 mmol) were added and the reaction mixture was stirred for 8 hours at 110° C. The reaction was quenched with water (1 ml), diluted with brine (5 ml) and extracted with ethyl acetate (2×10 ml). The organic layer was dried (Na2SO4), filtered and evaporated and the residue was purified by flash chromatography (Biotage system) on silica gel using a SNAP 10 g as column and dichloromethane/methanol from 99.5:0.5 to 95:5 as eluent affording the title compound (12 mg) as yellow pale solid.

Workup

  1. customThe reaction was quenched with water (1 ml)
  2. additiondiluted with brine (5 ml)
  3. extractionextracted with ethyl acetate (2×10 ml)
  4. dry with materialThe organic layer was dried (Na2SO4)
  5. filtrationfiltered
  6. customevaporated
  7. customthe residue was purified by flash chromatography (Biotage system) on silica gel using a SNAP 10 g as column and dichloromethane/methanol from 99.5:0.5 to 95:5 as eluent

Sources & evidence

ORD record
ord-eb3b529c9a7745c9b06ebcd13af443d0
Source dataset
uspto-grants-2016_08
Patent number
US09422252B2

Reaction notes

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