Hydrochloric Acid → 2-{(E)-2-[6-Methoxy-5-(4-methyl-1H-imidazol-1-yl)pyridin-2-yl]vinyl}-8-[2-(trifluoromethyl)phenyl]-5,6,7,8-tetrahydro[1,2,4]triazolo[1,5-a]pyridine

HRID 546799Notes

Reaction equation

HRID 546799 reaction equation
N1C=CN=C1.Cl.Cl[CH2:8][CH2:9][CH2:10][CH:11]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[C:23]([F:26])([F:25])[F:24])[C:12](=[NH:16])OCC.Cl.Cl.[CH3:29][O:30][C:31]1[N:36]=[C:35](/[CH:37]=[CH:38]/[C:39]([NH:41][NH2:42])=O)[CH:34]=[CH:33][C:32]=1[N:43]1[CH:47]=[C:46]([CH3:48])[N:45]=[CH:44]1.Cl>CO>[CH3:29][O:30][C:31]1[N:36]=[C:35](/[CH:37]=[CH:38]/[C:39]2[N:16]=[C:12]3[CH:11]([C:17]4[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=4[C:23]([F:24])([F:25])[F:26])[CH2:10][CH2:9][CH2:8][N:42]3[N:41]=2)[CH:34]=[CH:33][C:32]=1[N:43]1[CH:47]=[C:46]([CH3:48])[N:45]=[CH:44]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 795ImidazoleHCID 46854983Ethyl 5-chloro-2-(2-trifluoromethylphenyl)pentanimidoate hydrochlorideHCID 46854985(2E)-3-[6-Methoxy-5-(4-methyl-1H-imidazol-1-yl)pyridin-2-yl]acrylohydrazide dihydrochloride

Product 1

HCID 252130572-{(E)-2-[6-Methoxy-5-(4-methyl-1H-imidazol-1-yl)pyridin-2-yl]vinyl}-8-[2-(trifluoromethyl)phenyl]-5,6,7,8-tetrahydro[1,2,4]triazolo[1,5-a]pyridineYield 86%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
30 °C

Procedure

Imidazole (4.75 g, 69.7 mmol) and Ethyl 5-chloro-2-(2-trifluoromethylphenyl)pentanimidoate hydrochloride (2.00 g, 5.81 mmol) were added the solution of (2E)-3-[6-Methoxy-5-(4-methyl-1H-imidazol-1-yl)pyridin-2-yl]acrylohydrazide dihydrochloride in methanol (10 mL) at 0° C. under nitrogen atmosphere. The reaction mixture was stirred at 30° C. for 40 hours. The reaction mixture was adjusted to the pH6.5 with 5N HCl aq., and extracted with ethyl acetate (22 mL). The organic layer was washed with water (4 mL), concentrated under the reduced pressure and azeotroped with 2-propanol under the reduced pressure to obtain the title compound (2.4 g, 86% yield). Traces of seed crystal of the title compound which was obtained by the method similar to this step was added to the solution of the crude title compound in 2-propanol (10 mL), and the mixture was stirred at room temperature for 13.5 hours. The suspension was stirred for 2 hours with an ice-bath cooling. The solids were collected by filtration and washed with 2-propanol and dried under the reduced pressure to obtain the title compound (1.55 g, 56% yield).

Workup

  1. extractionextracted with ethyl acetate (22 mL)
  2. washThe organic layer was washed with water (4 mL)
  3. concentrationconcentrated under the reduced pressure
  4. customazeotroped with 2-propanol under the reduced pressure

Sources & evidence

ORD record
ord-3df7487fddfb40e789c8a055180f16e1
Source dataset
uspto-grants-2011_05
Patent number
US07935815B2

Reaction notes

Loading…