Isobutyl iodide → HCID 90115225, compound

HRID 1844217Notes

Reaction equation

HRID 1844217 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.I[CH2:30][CH:31]([CH3:33])[CH3:32]>C1(C)C=CC=CC=1.[I-].C([N+](CCCC)(CCCC)CCCC)CCC.[Ag-]=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][CH2:30][CH:31]([CH3:33])[CH3:32])[CH2:20][OH:21])=[O:17])=[C:13]([CH3:15])[N:14]=2)[CH:9]=[CH:10][CH:11]=1

Participants

6

Reactant 2

HCID 10556Isobutyl iodideHCID 90090900HCID 90090900, compound

Product 1

HCID 90115225HCID 90115225, compound

Reagents, catalysts & solvents 3

HCID 67553Tetrabutylammonium IodideCatalystHCID 178418778HCID 178418778, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
40 °C

Procedure

250 mg (0.64 mmol) of 8-[(2,6-difluorobenzyl)oxy]-N-(1,3-dihydroxy-propan-2-yl)-2-methylimidazo[1,2-a]pyridine-3-carboxamide and 4.94 g (26.83 mmol) of 1-iodo-2-methylpropane were initially charged in dry toluene, 1.87 g (7.66 mmol) of silver(I) oxide and 118 mg (0.32 mmol) of tetra-n-butylammonium iodide were added and the mixture was stirred at 40° C. overnight. The reaction mixture was filtered through Celite, the filter cake was washed thoroughly, the filtrate was concentrated and the residue was purified by preparative HPLC (RP18 column, mobile phase: acetonitrile/water gradient with addition of 0.1% TFA). The crude product was then purified by preparative thick-layer chromatography (mobile phase: dichloromethane:methanol=20:1). This gave 13 mg of the target compound (4.5% of theory, purity 100%).

Workup

  1. filtrationThe reaction mixture was filtered through Celite
  2. washthe filter cake was washed thoroughly
  3. concentrationthe filtrate was concentrated
  4. customthe residue was purified by preparative HPLC (RP18 column, mobile phase: acetonitrile/water gradient with addition of 0.1% TFA)
  5. customThe crude product was then purified by preparative thick-layer chromatography (mobile phase: dichloromethane:methanol=20:1)

Sources & evidence

ORD record
ord-9d463102bd1b4201b59ef76556179627
Source dataset
uspto-grants-2015_02
Patent number
US08946215B2

Reaction notes

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