Triethylamine → Methyl 3-{4-[(4-chloro-5-ethyl-1H-imidazole-2-carbonyl)amino]piperidin-1-yl}benzoate

HRID 43826Notes

Reaction equation

HRID 43826 reaction equation
[NH2:1][CH:2]1[CH2:7][CH2:6][N:5]([C:8]2[CH:9]=[C:10]([CH:15]=[CH:16][CH:17]=2)[C:11]([O:13][CH3:14])=[O:12])[CH2:4][CH2:3]1.[Cl:18][C:19]1[N:20]=[C:21]([C:26](O)=[O:27])[NH:22][C:23]=1[CH2:24][CH3:25].ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.C(N(CC)CC)C>CN(C)C(=O)C.ClCCl.O.C(O)(C(F)(F)F)=O.C(OCC)(=O)C>[Cl:18][C:19]1[N:20]=[C:21]([C:26]([NH:1][CH:2]2[CH2:7][CH2:6][N:5]([C:8]3[CH:9]=[C:10]([CH:15]=[CH:16][CH:17]=3)[C:11]([O:13][CH3:14])=[O:12])[CH2:4][CH2:3]2)=[O:27])[NH:22][C:23]=1[CH2:24][CH3:25]

Participants

9

Reactant 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 67339058Methyl 3-(4-aminopiperidin-1-yl)benzoateHCID 675489294-chloro-5-ethyl-1H-imidazole-2-carboxylic acid

Product 1

HCID 67549845Methyl 3-{4-[(4-chloro-5-ethyl-1H-imidazole-2-carbonyl)amino]piperidin-1-yl}benzoateYield 41%

Reagents, catalysts & solvents 3

HCID 8857Ethyl AcetateSolventHCID 22392675Trifluoroacetic acid waterSolventHCID 85741463dichloromethane N,N-dimethylacetamideSolvent

Procedure

10% palladium-carbon (wet, 200 mg) was added to a mixed solution of methyl 3-(4-benzyloxycarbonylaminopiperidin-1-yl)benzoate obtained in Example (192c) (120 mg, 0.345 mmol) in tetrahydrofuran/methanol=1/1 (10 mL), and the mixture was catalytically hydrogenated at room temperature for three hours. The catalyst was filtered off, and the filtrate was evaporated under reduced pressure to obtain methyl 3-(4-aminopiperidin-1-yl)benzoate as a colorless oily substance. The resulting amine was dissolved in a mixed solution of N,N-dimethylacetamide/dichloromethane=1/1 (8 mL). 4-Chloro-5-ethyl-1H-imidazole-2-carboxylic acid (described in Example 1d, 190 mg, 1.1 mmol), 1-hydroxybenzotriazole (220 mg, 1.63 mmol), 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (312 mg, 1.63 mmol) and triethylamine (227 μL, 1.63 mmol) were added, and the mixture was stirred at room temperature overnight. The reaction solution was diluted with ethyl acetate, washed with brine, and then dried over magnesium sulfate. The solvent was evaporated under reduced pressure. The resulting residue was purified by silica gel column chromatography (elution solvent: hexane/ethyl acetate=1/1) to obtain 88 mg of the title compound as a colorless solid (41%).

Workup

  1. washwashed with brine
  2. dry with materialdried over magnesium sulfate
  3. customThe solvent was evaporated under reduced pressure
  4. customThe resulting residue was purified by silica gel column chromatography (elution solvent: hexane/ethyl acetate=1/1)

Sources & evidence

ORD record
ord-32dea51ddcf247b091beab7a865e1fdc
Source dataset
uspto-grants-2013_09
Patent number
US08536197B2

Reaction notes

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