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

HRID 2246442Notes

Reaction equation

HRID 2246442 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>[Cl:24][CH2:25][C:26]1[NH:8][C:7]2[CH:6]=[C:5]([C:9]3[CH:14]=[CH:13][C:12]([O:15][CH2:16][CH3:17])=[C:11]([C:18]([F:21])([F:19])[F:20])[CH:10]=3)[N:4]=[C:3]([C:22]#[N:23])[C:2]=2[N:1]=1

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 41.9%

Reagents, catalysts & solvents 2

HCID 2733225Ytterbium triflateCatalystHCID 6342AcetonitrileSolvent

Procedure

3,4-Diamino-6-(4-ethoxy-3-trifluoromethyl-phenyl)-pyridine-2-carbonitrile (1 g, 3.1 mmol) was dissolved in acetonitrile (20 ml) and ytterbium triflate (38 mg, 0.062 mmol) and 2-chloro-1,1,1-triethoxyethane (1.83 g, 9.3 mmol) were added. The mixture was heated to reflux overnight. Mixture was evaporated under reduced pressure, partitioned between ethyl acetate (100 ml) and water (100 ml), and organics were dried then evaporated under reduced pressure to afford a dark brown oil. Triturated with DCM (50 ml) to afford 495 mg of 2-chloromethyl-6-(4-ethoxy-3-trifluoromethyl-phenyl)-1H-imidazo[4,5-c]pyridine-4-carbonitrile as a light brown solid. 1H NMR (DMSO) δ 8.47-8.33 (m, 3H), 7.41 (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 was heated
  2. temperatureto reflux overnight
  3. customMixture was evaporated under reduced pressure
  4. custompartitioned between ethyl acetate (100 ml) and water (100 ml)
  5. customorganics were dried
  6. customthen evaporated under reduced pressure
  7. customto afford a dark brown oil
  8. customTriturated with DCM (50 ml)

Sources & evidence

ORD record
ord-d1a330c923504fc7b7d6ee996ef2d4be
Source dataset
uspto-grants-2010_03
Patent number
US07687515B2

Reaction notes

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