Methanol → HCID 90115652, compound

HRID 1624136Notes

Reaction equation

HRID 1624136 reaction equation
[F:1][C:2]1[CH:27]=[CH:26][CH:25]=[C:24]([F:28])[C:3]=1[CH2:4][O:5][C:6]1[C:7]2[N:8]([C:12]([C:16]([NH:18][CH:19]([CH2:22][OH:23])[CH2:20][OH:21])=[O:17])=[C:13]([CH3:15])[N:14]=2)[CH:9]=[CH:10][CH:11]=1.[H-].[Na+].I[CH2:32][CH2:33][CH3:34].CO>CN(C=O)C.O>[F:1][C:2]1[CH:27]=[CH:26][CH:25]=[C:24]([F:28])[C:3]=1[CH2:4][O:5][C:6]1[C:7]2[N:8]([C:12]([C:16]([NH:18][CH:19]([CH2:22][O:23][CH2:32][CH2:33][CH3:34])[CH2:20][OH:21])=[O:17])=[C:13]([CH3:15])[N:14]=2)[CH:9]=[CH:10][CH:11]=1

Participants

7

Reactant 4

HCID 887MethanolHCID 24758Sodium hydride3×HCID 336431-Iodopropane3×HCID 90090900HCID 90090900, compound

Product 1

HCID 90115652HCID 90115652, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

At 0° C., 100 mg (0.26 mmol) of 8-[(2,6-difluorobenzyl)oxy]-N-(1,3-dihydroxypropan-2-yl)-2-methylimidazo[1,2-a]pyridine-3-carboxamide were initially charged in 2.4 ml of DMF, 7.1 mg (0.28 mmol) of sodium hydride (95%) were added and the mixture was stirred at 0° C. for 30 min. At 0° C., a solution of 35 mg (0.20 mmol) of iodopropane in 0.4 ml of DMF was then slowly added dropwise, and the mixture was stirred at RT overnight. Another 1.6 mg (0.064 mmol) of sodium hydride (95%) were added at room temperature, the mixture was stirred for 30 min, another 10.6 mg (0.064 mmol) of iodopropane were then added dropwise and the mixture was stirred at room temperature overnight. At RT, another 1.6 mg (0.064 mmol) of sodium hydride (95%) were then added, the mixture was stirred for 30 min and 10.6 mg (0.064 mmol) of iodopropane were then added dropwise, and the mixture was stirred at room temperature overnight. A little methanol was added, and the reaction mixture was poured into 20 ml of water and extracted twice with ethyl acetate. The combined organic phases were washed with aqueous saturated sodium chloride solution, dried over sodium sulphate, filtered and concentrated. The residue was purified by silica gel chromatography (mobile phase: cyclohexane:ethyl acetate=7:3, then dichloromethane:methanol=40:1). The crude product obtained was re-purified by preparative thick-layer chromatography (dichloromethane:methanol=20:1). This gave 44 mg of the target compound (38% of theory, purity 95%).

Workup

  1. stirringthe mixture was stirred at RT overnight
  2. stirringthe mixture was stirred for 30 min
  3. stirringthe mixture was stirred at room temperature overnight
  4. stirringthe mixture was stirred for 30 min
  5. stirringthe mixture was stirred at room temperature overnight
  6. extractionextracted twice with ethyl acetate
  7. washThe combined organic phases were washed with aqueous saturated sodium chloride solution
  8. dry with materialdried over sodium sulphate
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe residue was purified by silica gel chromatography (mobile phase

Sources & evidence

ORD record
ord-d48006b6889e4cfb8dd0ec09456bad7f
Source dataset
uspto-grants-2014_07
Patent number
US08778964B2

Reaction notes

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