Methyl iodide → HCID 178459020, compound

HRID 81239Notes

Reaction equation

HRID 81239 reaction equation
[Si]([O:8][CH2:9][C:10]([C:12]1[N:29]([CH2:30][C@H:31]2[CH2:36][CH2:35][C@H:34]([CH3:37])[CH2:33][CH2:32]2)[C:15]2[C:16]([C:22]3[CH:23]=[N:24][CH:25]=[C:26]([Cl:28])[CH:27]=3)=[N:17][C:18]([C:20]#[N:21])=[CH:19][C:14]=2[N:13]=1)=[CH2:11])(C(C)(C)C)(C)C.[F-].[CH2:39]([N+](CCCC)(CCCC)CCCC)CCC.[H-].[Na+].CI>C1COCC1>[Cl:28][C:26]1[CH:27]=[C:22]([C:16]2[C:15]3[N:29]([CH2:30][C@H:31]4[CH2:36][CH2:35][C@H:34]([CH3:37])[CH2:33][CH2:32]4)[C:12]([C:10]([CH2:9][O:8][CH3:39])=[CH2:11])=[N:13][C:14]=3[CH:19]=[C:18]([C:20]#[N:21])[N:17]=2)[CH:23]=[N:24][CH:25]=1

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 2724141Tetrabutylammonium FluorideHCID 178460611HCID 178460611, compound2×

Product 1

HCID 178459020HCID 178459020, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Steps 5 & 6: A stirred solution of 2-(3-{[tert-butyl(dimethyl)silyl]oxy}prop-1-en-2-yl)-4-(5-chloropyridin-3-yl)-3-[(trans-4-methylcyclohexyl)methyl]-3H-imidazo[4,5-c]pyridine-6-carbonitrile (1.2 g, 2.24 mmol) in THF (20 mL) was cooled to 0° C. Tetrabutylammonium fluoride (3.36 mL, 3.36 mmol, 1M solution in THF) was added dropwise over a period of 5 minutes, and the reaction mixture was warmed to room temperature and stirred for 1 h. The reaction mixture was quenched with water (10 mL) and extracted with ethyl acetate (15 mL). The organic phase was separated, washed with brine solution (10 mL), dried over anhydrous Na2SO4, filtered, and concentrated. The crude 4-(5-chloropyridin-3-yl)-2-(3-hydroxyprop-1-en-2-yl)-3-[(trans-4-methylcyclohexyl)methyl]-3H-imidazo[4,5-c]pyridine-6-carbonitrile (0.9 g, 2.14 mmol) was dissolved in dry THF (10 mL) and cooled to 0° C. NaH (0.123 g, 3.12 mmol, 60% in mineral oil) was added in several portions and stirred for 15 minutes. Methyl iodide (0.16 mL, 2.57 mmol) was added dropwise over a period of 5 minutes, and the reaction mixture was slowly warmed to room temperature and stirred for 1 h. The reaction mixture was quenched with ice and extracted with ethyl acetate (100 mL). The organic layer was separated, washed with brine (20 mL), dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography using 15% ethyl acetate/petroleum ether as eluent to yield 4-(5-chloropyridin-3-yl)-2-(3-methoxyprop-1-en-2-yl)-3-[(trans-4-methylcyclohexyl)methyl]-3H-imidazo[4,5-c]pyridine-6-carbonitrile. MS ES/APCl calcd. for C24H26ClN5O [M+H]+ 436. found 436

Workup

  1. customThe reaction mixture was quenched with water (10 mL)
  2. extractionextracted with ethyl acetate (15 mL)
  3. customThe organic phase was separated
  4. washwashed with brine solution (10 mL)
  5. dry with materialdried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. temperaturecooled to 0° C
  9. stirringstirred for 15 minutes
  10. temperaturethe reaction mixture was slowly warmed to room temperature
  11. stirringstirred for 1 h
  12. customThe reaction mixture was quenched with ice
  13. extractionextracted with ethyl acetate (100 mL)
  14. customThe organic layer was separated
  15. washwashed with brine (20 mL)
  16. dry with materialdried over anhydrous Na2SO4
  17. filtrationfiltered
  18. concentrationconcentrated under reduced pressure
  19. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-769df5dae6834c9fb86b94fde65bd7fe
Source dataset
uspto-grants-2014_09
Patent number
US08846657B2

Reaction notes

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