Dimethylformamide → HCID 72703918, compound

HRID 1484521Notes

Reaction equation

HRID 1484521 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][C:20]=1[CH3:32]>>[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][C:20]=3[CH3:32])=[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 727043324-(6-fluoro-5-methyl-3-pyridyl)-3-methyl-1H-1,2,4-triazol-5-one2×

Product 1

HCID 72703918HCID 72703918, compoundYield 11%

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, 0.365 mmol) and then 4-(6-fluoro-5-methyl-3-pyridyl)-3-methyl-1H-1,2,4-triazol-5-one (Intermediate 9, 38.0 mg, 0.18 mmol) were added and the reaction mixture was stirred for 16 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 (7 mg) as a 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-dff820d112e242dd850f6de74acf3000
Source dataset
uspto-grants-2016_08
Patent number
US09422252B2

Reaction notes

Loading…