1-Hydroxybenzotriazole → (E)-3-[6-methoxy-5-(4-methyl-1H-imidazol-1-yl)pyridin-2-yl]-N-[2-oxo-3-(2-trifluoromethylphenyl)piperidin-1-yl]acrylamide

HRID 2369348Notes

Reaction equation

HRID 2369348 reaction equation
C1C=CC2N(O)N=NC=2C=1.C(N(C(C)C)CC)(C)C.FC(F)(F)C(O)=O.[CH3:27][O:28][C:29]1[N:34]=[C:33](/[CH:35]=[CH:36]/[C:37]([OH:39])=O)[CH:32]=[CH:31][C:30]=1[N:40]1[CH:44]=[C:43]([CH3:45])[N:42]=[CH:41]1.[NH2:46][N:47]1[CH2:52][CH2:51][CH2:50][CH:49]([C:53]2[CH:58]=[CH:57][CH:56]=[CH:55][C:54]=2[C:59]([F:62])([F:61])[F:60])[C:48]1=[O:63].C(=O)(O)[O-].[Na+]>CN(C=O)C.C(OCC)(=O)C.C(Cl)CCl>[CH3:27][O:28][C:29]1[N:34]=[C:33](/[CH:35]=[CH:36]/[C:37]([NH:46][N:47]2[CH2:52][CH2:51][CH2:50][CH:49]([C:53]3[CH:58]=[CH:57][CH:56]=[CH:55][C:54]=3[C:59]([F:60])([F:61])[F:62])[C:48]2=[O:63])=[O:39])[CH:32]=[CH:31][C:30]=1[N:40]1[CH:44]=[C:43]([CH3:45])[N:42]=[CH:41]1

Participants

9

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 666173261-Amino-3-(2-trifluoromethylphenyl)piperidin-2-oneHCID 66633905(E)-3-[6-methoxy-5-(4-methyl-1H-imidazol-1-yl)pyridin-2-yl]acrylic acid trifluoroacetate

Product 1

HCID 66617336(E)-3-[6-methoxy-5-(4-methyl-1H-imidazol-1-yl)pyridin-2-yl]-N-[2-oxo-3-(2-trifluoromethylphenyl)piperidin-1-yl]acrylamideYield 84.8%

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

EDC (834 mg), HOBT (588 mg) and IPEA (2.03 mL) were added to a suspension of (E)-3-[6-methoxy-5-(4-methyl-1H-imidazol-1-yl)pyridin-2-yl]acrylic acid trifluoroacetate (1.42 g) and 1-amino-3-(2-trifluoromethylphenyl)piperidin-2-one (750 mg) in DMF (30 mL). After stirring at room temperature for 14 hours, a saturated sodium bicarbonate solution and ethyl acetate were added to the reaction solution, and the organic layer was separated. The resulting organic layer was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (carrier: Chromatorex NH; elution solvent: ethyl acetate-methanol system) to obtain 1.23 g of the title compound. The property values of the compound are as follows.

Workup

  1. customthe organic layer was separated
  2. dry with materialThe resulting organic layer was dried over anhydrous magnesium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified by silica gel column chromatography (carrier: Chromatorex NH; elution solvent: ethyl acetate-methanol system)

Sources & evidence

ORD record
ord-32a6ecb9b1fe42e19e3efb32845787eb
Source dataset
uspto-grants-2014_04
Patent number
US08703954B2

Reaction notes

Loading…