1-Hydroxybenzotriazole → 1-Methyl-N-(tetrahydro-2H-pyran-4-yl)-N-[3-(trifluoromethoxy)benzyl]-1H-imidazole-4-carboxamide

HRID 467958

Reaction equation

HRID 467958 reaction equation
[F:1][C:2]([F:19])([F:18])[O:3][C:4]1[CH:5]=[C:6]([CH:15]=[CH:16][CH:17]=1)[CH2:7][NH:8][CH:9]1[CH2:14][CH2:13][O:12][CH2:11][CH2:10]1.[CH3:20][N:21]1[CH:25]=[C:24]([C:26](O)=[O:27])[N:23]=[CH:22]1.CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1>C(#N)C>[CH3:20][N:21]1[CH:25]=[C:24]([C:26]([N:8]([CH:9]2[CH2:14][CH2:13][O:12][CH2:11][CH2:10]2)[CH2:7][C:6]2[CH:15]=[CH:16][CH:17]=[C:4]([O:3][C:2]([F:18])([F:1])[F:19])[CH:5]=2)=[O:27])[N:23]=[CH:22]1

Participants

6

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 5415091-methyl-1H-imidazole-4-carboxylic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 58049381N-[3-(Trifluoromethoxy)benzyl]tetrahydro-2H-pyran-4-amine

Product 1

HCID 469166841-Methyl-N-(tetrahydro-2H-pyran-4-yl)-N-[3-(trifluoromethoxy)benzyl]-1H-imidazole-4-carboxamideYield 14.4%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of N-[3-(trifluoromethoxy)benzyl]tetrahydro-2H-pyran-4-amine (450 mg), 1-methyl-1H-imidazole-4-carboxylic acid (210 mg), EDC.HCl (320 mg), HOBt (250 mg) and acetonitrile (5 mL) was stirred at room temperature for an hour. Acetonitrile was distilled off under reduced pressure and an aqueous solution of 6 M sodium hydroxide was added. Extraction was conducted with ethyl acetate and the solvent was concentrated. The residue was purified by column chromatography (NH silica gel cartridge; ethyl acetate) to give the titled compound (90 mg).

Workup

  1. distillationAcetonitrile was distilled off under reduced pressure
  2. additionan aqueous solution of 6 M sodium hydroxide was added
  3. extractionExtraction
  4. concentrationthe solvent was concentrated
  5. customThe residue was purified by column chromatography (NH silica gel cartridge; ethyl acetate)

Sources & evidence

ORD record
ord-3e3ee17d43a4428ba849d0dfde4e66d7
Source dataset
uspto-grants-2014_01
Patent number
US08623898B2

Linked notes

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