2-Chloro-1,1,1-triethoxyethane → 2-chloromethyl-6-(4-ethoxy-3-trifluoromethyl-phenyl)-1H-imidazo[4,5-c]pyridine-4-carbonitrile

HRID 2246434Notes

Reaction equation

HRID 2246434 reaction equation
[NH2:1][C:2]1[C:3]([C:22]#[N:23])=[N:4][C:5]([C:9]2[CH:14]=[CH:13][C:12]([O:15][CH2:16][CH3:17])=[C:11]([C:18]([F:21])([F:20])[F:19])[CH:10]=2)=[CH:6][C:7]=1[NH2:8].[Cl:24][CH2:25][C:26](OCC)(OCC)OCC>C(#N)C.[O-]S(C(F)(F)F)(=O)=O.[Yb+3].[O-]S(C(F)(F)F)(=O)=O.[O-]S(C(F)(F)F)(=O)=O>[CH2:16]([O:15][C:12]1[CH:13]=[CH:14][C:9]([C:5]2[N:4]=[C:3]([C:22]#[N:23])[C:2]3[N:1]=[C:26]([CH2:25][Cl:24])[NH:8][C:7]=3[CH:6]=2)=[CH:10][C:11]=1[C:18]([F:21])([F:19])[F:20])[CH3:17]

Participants

5

Reactant 2

HCID 3059222-Chloro-1,1,1-triethoxyethaneHCID 589381183,4-Diamino-6-(4-ethoxy-3-trifluoromethyl-phenyl)-pyridine-2-carbonitrile

Product 1

HCID 589381142-chloromethyl-6-(4-ethoxy-3-trifluoromethyl-phenyl)-1H-imidazo[4,5-c]pyridine-4-carbonitrileYield 54.5%

Reagents, catalysts & solvents 2

HCID 2733225Ytterbium triflateCatalystHCID 6342AcetonitrileSolvent

Procedure

To a solution of 3,4-diamino-6-(4-ethoxy-3-trifluoromethyl-phenyl)-pyridine-2-carbonitrile (1.86 g, 5.78 mmol) and 2-chloro-1,1,1-triethoxyethane (3.41 g, 17.3 mmol) in acetonitrile (40 ml) was added ytterbium triflate (180 mg, 5 mol %) and the mixture heated to reflux overnight. The mixture was concentrated under reduced pressure before partitioning between ethyl acetate and water. The organic layer was dried over sodium sulfate and concentrated before addition of diethylether. The precipitate was filtered and dried under a stream of air to afford 6-(4-ethoxy-3-trifluoromethyl-phenyl)-2-(chloromethyl)-1H-imidazo[4,5,c]pyridine-4-carbonitrile (1.2 g). 1H NMR (DMSO): δ 8.42 (s, 1H) 8.38 (d, 1H) 8.34 (s, 1H) 7.40 (d, 1H) 5.05 (s, 2H) 4.26 (q, 2H) 1.38 (t, 3H). MS m/z 381.1 (M+1)

Workup

  1. temperaturethe mixture heated
  2. temperatureto reflux overnight
  3. concentrationThe mixture was concentrated under reduced pressure
  4. custombefore partitioning between ethyl acetate and water
  5. dry with materialThe organic layer was dried over sodium sulfate
  6. concentrationconcentrated before addition of diethylether
  7. filtrationThe precipitate was filtered
  8. customdried under a stream of air

Sources & evidence

ORD record
ord-6f06db11150c47f4a8e4e89fe045d39d
Source dataset
uspto-grants-2010_03
Patent number
US07687515B2

Reaction notes

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