1,1,1-Trimethoxy-2-chloroethane → 2-Chloromethyl-1-ethyl-6-(3-trifluoromethyl-phenyl)-1H-imidazo[4,5-c]pyridine-4-carbonitrile

HRID 2246457Notes

Reaction equation

HRID 2246457 reaction equation
[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:26][CH2:27][C:28](OC)(OC)OC.[NH2:35][C:36]1[C:37]([C:55]#[N:56])=[N:38][C:39]([C:45]2[CH:50]=[CH:49][CH:48]=[C:47]([C:51]([F:54])([F:53])[F:52])[CH:46]=2)=[CH:40][C:41]=1[NH:42][CH2:43][CH3:44]>C(#N)C>[Cl:26][CH2:27][C:28]1[N:42]([CH2:43][CH3:44])[C:41]2[CH:40]=[C:39]([C:45]3[CH:50]=[CH:49][CH:48]=[C:47]([C:51]([F:54])([F:52])[F:53])[CH:46]=3)[N:38]=[C:37]([C:55]#[N:56])[C:36]=2[N:35]=1

Participants

5

Reactant 3

HCID 1447021,1,1-Trimethoxy-2-chloroethaneHCID 2733225Ytterbium triflateHCID 685171643-Amino-4-ethylamino-6-(3-trifluoromethylphenyl)-pyridine-2-carbonitrile

Product 1

HCID 685169312-Chloromethyl-1-ethyl-6-(3-trifluoromethyl-phenyl)-1H-imidazo[4,5-c]pyridine-4-carbonitrileYield 87%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Ytterbium triflate (1.16 g, 1.8 mmol) and 2-chloro-1,1,1-trimethoxyethane (7.56 mL, 56.0 mmol) was added to a solution of 3-amino-4-ethylamino-6-(3-trifluoromethylphenyl)-pyridine-2-carbonitrile (5.73 g, 18.7 mmol) in acetonitrile (150 mL). The mixture was refluxed for 48 hours, then concentrated under reduced pressure. The residue was partitioned between ethyl acetate and water. The organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was triturated with diethyl ether, filtered off to afford the title compound (5.92 g, 87%) as a solid. 1H NMR (DMSO-d6) δ: 8.85 (s, 1H); 8.50-8.00 (m, 2H); 7.90-7.70 (m, 2H); 5.26 (s, 2H); 4,55-4.45 (m, 2H); 1.48 (t, J=7 Hz, 3H). MS m/z: 365 (M+1).

Workup

  1. temperatureThe mixture was refluxed for 48 hours
  2. concentrationconcentrated under reduced pressure
  3. customThe residue was partitioned between ethyl acetate and water
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was triturated with diethyl ether
  8. filtrationfiltered off

Sources & evidence

ORD record
ord-b7415f9f57fc40bdad8908c685e69f13
Source dataset
uspto-grants-2010_03
Patent number
US07687515B2

Reaction notes

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