Methyl iodide → HCID 59497534, compound

HRID 1747480Notes

Reaction equation

HRID 1747480 reaction equation
C([O:3][C:4](=[O:31])[CH2:5][CH:6]([N:10]1[C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=2[N:12]([CH2:19][C:20]2[CH:28]=[C:27]([Cl:29])[CH:26]=[C:25]3[C:21]=2[CH:22]=[CH:23][NH:24]3)[C:11]1=[O:30])[CH2:7][CH2:8][CH3:9])C.[C:32]([O-])([O-])=O.[K+].[K+].CI>C(#N)C.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC>[Cl:29][C:27]1[CH:26]=[C:25]2[C:21]([CH:22]=[CH:23][N:24]2[CH3:32])=[C:20]([CH2:19][N:12]2[C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[N:10]([CH:6]([CH2:7][CH2:8][CH3:9])[CH2:5][C:4]([OH:3])=[O:31])[C:11]2=[O:30])[CH:28]=1

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 59497483HCID 59497483, compound

Product 1

HCID 59497534HCID 59497534, compoundYield 9%

Reagents, catalysts & solvents 2

HCID 74236Tetrabutylammonium BromideCatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
65 °C

Procedure

3-[3-(6-Chloro-1H-indol-4-ylmethyl)-2-oxo-2,3-dihydro-benzimidazol-1-yl]-hexanoic acid ethyl ester (300 mg, 0.68 mmol), prepared as described in example 72 using the appropriate reagents, was dissolved in acetonitrile (5 mL) and treated with K2CO3 (700 mg, 5.1 mmol), methyl iodide (0.31 mL, 5 mmol) and tetrabutylammonium bromide (161 mg, 0.5 mmol). The resulting mixture was heated at 65° C. for 60 h, filtered, and the solution was treated directly with Amberlyst® A26 (OH— form) (1.5 g, 2 mmol). This mixture was agitated for 18 h, filtered and the resin was washed with several portions of methanol. The product was eluted from the resin with 20% formic acid in methanol (2×2 mL). The eluant was concentrated and the residue was purified by preparative HPLC to provide 26 mg (9%) of the title compound. LCMS (ESMS): m/z 426 (M+H).

Workup

  1. filtrationfiltered
  2. additionthe solution was treated directly with Amberlyst® A26 (OH— form) (1.5 g, 2 mmol)
  3. filtrationfiltered
  4. washthe resin was washed with several portions of methanol
  5. washThe product was eluted from the resin with 20% formic acid in methanol (2×2 mL)
  6. concentrationThe eluant was concentrated
  7. customthe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-706f3fdbd0984bc3a88d5a63e8b82a03
Source dataset
uspto-grants-2015_10
Patent number
US09150556B2

Reaction notes

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