Triethylamine → (-)-2-{(E)-2-[5-methoxy-6-(4-methyl-1H-imidazol-1-yl)pyridin-3-yl]vinyl}-7-(3,4,5-trifluorophenyl)-6,7-dihydro-5H-pyrrolo[1,2-b][1,2,4]triazole

HRID 546765Notes

Reaction equation

HRID 546765 reaction equation
Cl.Cl[CH2:3][CH2:4][CH:5]([C:10]1[CH:15]=[C:14]([F:16])[C:13]([F:17])=[C:12]([F:18])[CH:11]=1)[C:6]([NH:8][NH2:9])=O.C(N(CC)CC)C.Cl.Cl.[CH3:28][O:29][C:30]1[CH:31]=[C:32](/[CH:42]=[CH:43]/[C:44](=[NH:48])OCC)[CH:33]=[N:34][C:35]=1[N:36]1[CH:40]=[C:39]([CH3:41])[N:38]=[CH:37]1>C(O)C>[CH3:28][O:29][C:30]1[CH:31]=[C:32](/[CH:42]=[CH:43]/[C:44]2[N:48]=[C:6]3[CH:5]([C:10]4[CH:15]=[C:14]([F:16])[C:13]([F:17])=[C:12]([F:18])[CH:11]=4)[CH2:4][CH2:3][N:8]3[N:9]=2)[CH:33]=[N:34][C:35]=1[N:36]1[CH:40]=[C:39]([CH3:41])[N:38]=[CH:37]1

Participants

5

Reactant 3

HCID 8471Triethylamine2×HCID 66839084ethyl (E)-3-[5-methoxy-6-(4-methyl-1H-imidazol-1-yl)pyridin-3-yl]acrylimidate dihydrochlorideHCID 668395654-Chloro-2-(3,4,5-trifluorophenyl)butyric acid hydrazide hydrochloride

Product 1

HCID 66839615(-)-2-{(E)-2-[5-methoxy-6-(4-methyl-1H-imidazol-1-yl)pyridin-3-yl]vinyl}-7-(3,4,5-trifluorophenyl)-6,7-dihydro-5H-pyrrolo[1,2-b][1,2,4]triazole

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Conditions

Temperature
80 °C

Procedure

A solution of 4-chloro-2-(3,4,5-trifluorophenyl)butyric acid hydrazide hydrochloride synthesized in Examples 253 and 254 (565 mg) and triethylamine (1.0 mL) in ethanol (10 mL) was added to a solution of ethyl (E)-3-[5-methoxy-6-(4-methyl-1H-imidazol-1-yl)pyridin-3-yl]acrylimidate dihydrochloride (500 mg) and triethylamine (0.95 mL) in ethanol (10 mL) at room temperature. The reaction solution was stirred at 80° C. for 25 hours. The reaction solution was left to cool to room temperature and then concentrated under reduced pressure. A saturated sodium bicarbonate solution was added to the resulting residue, followed by extraction with chloroform. The resulting extract was dried over magnesium sulfate and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (carrier: Chromatorex NH; elution solvent: heptane-ethyl acetate system) to obtain 154 mg of the racemic title compound. The racemic title compound (154 mg) was purified by CHIRALPAK™ IA manufactured by Daicel Chemical Industries, Ltd. (2 cm×25 cm; mobile phase: hexane:ethanol=1:1) and then separated by CHIRALPAK™ IB manufactured by Daicel Chemical Industries, Ltd. (2 cm×25 cm; mobile phase: hexane:ethanol=7:3) to obtain the title optically active compound with a retention time of 17 minutes and positive optical rotation (40 mg) and the title optically active compound with a retention time of 23 minutes and negative optical rotation (37 mg).

Workup

  1. waitThe reaction solution was left
  2. temperatureto cool to room temperature
  3. concentrationconcentrated under reduced pressure
  4. additionA saturated sodium bicarbonate solution was added to the resulting residue
  5. extractionfollowed by extraction with chloroform
  6. extractionThe resulting extract
  7. dry with materialwas dried over magnesium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by silica gel column chromatography (carrier: Chromatorex NH; elution solvent: heptane-ethyl acetate system)

Sources & evidence

ORD record
ord-c3acefa6d3a54898b723422463648c89
Source dataset
uspto-grants-2011_05
Patent number
US07935815B2

Reaction notes

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