Diisopropylethylamine → (E)-N-[3-(3,4-difluorophenyl)-2-oxopiperidin-1-yl]-3-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl]acrylamide

HRID 599629Notes

Reaction equation

HRID 599629 reaction equation
C(N(C(C)C)CC)(C)C.[NH2:10][N:11]1[CH2:16][CH2:15][CH2:14][CH:13]([C:17]2[CH:22]=[CH:21][C:20]([F:23])=[C:19]([F:24])[CH:18]=2)[C:12]1=[O:25].C1N(P(Cl)(N2C(=O)OCC2)=O)C(=O)OC1.[CH3:41][O:42][C:43]1[CH:44]=[C:45](/[CH:55]=[CH:56]/[C:57](O)=[O:58])[CH:46]=[CH:47][C:48]=1[N:49]1[CH:53]=[C:52]([CH3:54])[N:51]=[CH:50]1>C(Cl)Cl.O>[F:24][C:19]1[CH:18]=[C:17]([CH:13]2[CH2:14][CH2:15][CH2:16][N:11]([NH:10][C:57](=[O:58])/[CH:56]=[CH:55]/[C:45]3[CH:46]=[CH:47][C:48]([N:49]4[CH:53]=[C:52]([CH3:54])[N:51]=[CH:50]4)=[C:43]([O:42][CH3:41])[CH:44]=3)[C:12]2=[O:25])[CH:22]=[CH:21][C:20]=1[F:23]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 152842Bis(2-oxo-3-oxazolidinyl)phosphinic chlorideHCID 59528030(E)-3-[3-methoxy-4-(4-methylimidazol-1-yl)phenyl]acrylic acidHCID 668393321-Amino-3-(3,4-difluorophenyl)piperidin-2-one

Product 1

HCID 67067196(E)-N-[3-(3,4-difluorophenyl)-2-oxopiperidin-1-yl]-3-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl]acrylamideYield 70.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

IPEA (1.5 mL), 1-amino-3-(3,4-difluorophenyl)piperidin-2-one (420 mg) and BOPCl (0.53 g) were added to a solution of (E)-3-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl]acrylic acid (450 mg) in methylene chloride (15 mL) at room temperature, and the reaction solution was stirred at room temperature for three hours. Water was added to the reaction solution, followed by extraction with chloroform. The resulting extract was washed with a saturated sodium chloride solution. The resulting organic layer 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, then ethyl acetate-methanol system) to obtain 572 mg of the title compound. The property value of the compound is as follows.

Workup

  1. extractionfollowed by extraction with chloroform
  2. extractionThe resulting extract
  3. washwas washed with a saturated sodium chloride solution
  4. dry with materialThe resulting organic layer was dried over magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (carrier
  7. washelution solvent

Sources & evidence

ORD record
ord-b8445cc797d6416791bef629fb232412
Source dataset
uspto-grants-2011_03
Patent number
US07897632B2

Reaction notes

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