2-Methoxyethylamine → 4-{[4-(2-methoxy-ethylcarbamoyl)-1H-benzimidazol-2-ylamino)-methyl}-piperidine-1-carboxylic acid tert-butyl ester

HRID 2110003Notes

Reaction equation

HRID 2110003 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][NH:15][C:16]2[NH:20][C:19]3[CH:21]=[CH:22][CH:23]=[C:24]([C:25]([OH:27])=O)[C:18]=3[N:17]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].O.ON1C2C=CC=CC=2N=N1.[CH3:39][O:40][CH2:41][CH2:42][NH2:43].Cl.C(N=C=NCCCN(C)C)C>C(OCC)(=O)C.O.O1CCCC1.CN(C)C=O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][NH:15][C:16]2[NH:20][C:19]3[CH:21]=[CH:22][CH:23]=[C:24]([C:25](=[O:27])[NH:43][CH2:42][CH2:41][O:40][CH3:39])[C:18]=3[N:17]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

9

Reactant 4

HCID 80182-MethoxyethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 690661932-[(1-tert-butoxycarbonyl-piperidin-4-ylmethyl)-amino]-1H-benzimidazole-4-carboxylic acid

Product 1

HCID 690661524-{[4-(2-methoxy-ethylcarbamoyl)-1H-benzimidazol-2-ylamino)-methyl}-piperidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

After suspending 2-[(1-tert-butoxycarbonyl-piperidin-4-ylmethyl)-amino]-1H-benzimidazole-4-carboxylic acid (1.20 g, 3.20 mmol) in a mixed solvent of dimethylformamide and tetrahydrofuran (1:1, 20 ml), 1-hydroxybenzotriazole monohydrate (737 mg, 4.81 mmol) and 2-methoxyethylamine (0.42 ml, 4.8 mmol) were added. 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (1.90 g, 6.40 mmol) was further added, and then the mixture was stirred at room temperature for 4 hours. Water (100 ml) was added to the reaction mixture, extraction was preferred with ethyl acetate (150 ml×3 times), and the organic layer was washed with saturated brine (100 ml) and then dried over anhydrous magnesium sulfate. The residue obtained by concentrating this under reduced pressure was purified by silica gel column chromatography (ethyl acetate/methanol=30/1) to obtain 4-{[4-(2-methoxy-ethylcarbamoyl)-1H-benzimidazol-2-ylamino)-methyl}-piperidine-1-carboxylic acid tert-butyl ester. The compound was identified by LC-MS.

Workup

  1. additionwere added
  2. washthe organic layer was washed with saturated brine (100 ml)
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customThe residue obtained
  5. concentrationby concentrating this under reduced pressure
  6. customwas purified by silica gel column chromatography (ethyl acetate/methanol=30/1)

Sources & evidence

ORD record
ord-47fe38262ad748449b88236ca533c0f4
Source dataset
uspto-grants-2009_04
Patent number
US07517875B2

Reaction notes

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