Methanol → HCID 90115698, compound

HRID 1844215Notes

Reaction equation

HRID 1844215 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][CH3:33].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][OH:23])[CH2:20][O:21][CH2:32][CH3:33])=[O:17])=[C:13]([CH3:15])[N:14]=2)[CH:9]=[CH:10][CH:11]=1

Participants

7

Reactant 4

HCID 887MethanolHCID 6340Iodoethane2×HCID 24758Sodium hydride2×HCID 90090900HCID 90090900, compound

Product 1

HCID 90115698HCID 90115698, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

At 0° C., 750 mg (1.92 mmol) of 8-[(2,6-difluorobenzyl)oxy]-N-(1,3-dihydroxy-propan-2-yl)-2-methylimidazo[1,2-a]pyridine-3-carboxamide were initially charged in 19 ml of DMF, 52 mg (2.11 mmol) of sodium hydride (95%) were added and the mixture was stirred at 0° C. for 30 min. A solution of 239 mg (1.53 mmol) of iodoethane in 2 ml of DMF was then slowly added dropwise at 0° C., and the mixture was stirred at RT overnight. At room temperature, another 9.4 mg (0.38 mmol) of sodium hydride (95%) were added, the mixture was stirred for 30 min and another 59.8 mg (0.38 mmol) of iodoethane 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 dichloromethane:methanol=40:1, 20:1). This gave 280 mg of the target compound (33% of theory, purity 96%).

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. extractionextracted twice with ethyl acetate
  5. washThe combined organic phases were washed with aqueous saturated sodium chloride solution
  6. dry with materialdried over sodium sulphate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by silica gel chromatography (mobile phase dichloromethane:methanol=40:1, 20:1)

Sources & evidence

ORD record
ord-24989c68a009417ea9be8937b5d2703f
Source dataset
uspto-grants-2015_02
Patent number
US08946215B2

Reaction notes

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