Triethylamine → N-[(3S,6R)-1-(cyclopropylmethyl)-2-oxo-6-phenylazepan-3-yl]-4-(2-oxo-4-phenyl-2,3-dihydro-1H-imidazol-1-yl)piperidine-1-carboxamide

HRID 1725653Notes

Reaction equation

HRID 1725653 reaction equation
C(N(CC)CC)C.[NH2:8][CH:9]1[CH2:15][CH2:14][CH:13]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH2:12][N:11]([CH2:22][CH:23]2[CH2:25][CH2:24]2)[C:10]1=[O:26].Cl[C:28](OC1C=CC([N+]([O-])=O)=CC=1)=[O:29].[Cl-].[O:41]=[C:42]1[NH:46][C:45]([C:47]2[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=2)=[CH:44][N:43]1[CH:53]1[CH2:58][CH2:57][NH2+:56][CH2:55][CH2:54]1>O1CCCC1>[CH:23]1([CH2:22][N:11]2[CH2:12][C@@H:13]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[CH2:14][CH2:15][C@H:9]([NH:8][C:28]([N:56]3[CH2:57][CH2:58][CH:53]([N:43]4[CH:44]=[C:45]([C:47]5[CH:48]=[CH:49][CH:50]=[CH:51][CH:52]=5)[NH:46][C:42]4=[O:41])[CH2:54][CH2:55]3)=[O:29])[C:10]2=[O:26])[CH2:25][CH2:24]1

Participants

6

Reactant 4

HCID 8471Triethylamine2×HCID 821294-Nitrophenyl chloroformateHCID 184519153-Amino-1-(cyclopropylmethyl)-6-phenylazepan-2-oneHCID 673433224-(2-oxo-4-phenyl-2,3-dihydro-1H-imidazol-1-yl)piperidinium chloride

Product 1

HCID 11455312N-[(3S,6R)-1-(cyclopropylmethyl)-2-oxo-6-phenylazepan-3-yl]-4-(2-oxo-4-phenyl-2,3-dihydro-1H-imidazol-1-yl)piperidine-1-carboxamideYield 18.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Triethylamine (0.070 mL, 0.51 mmol) was added to a solution of 3-amino-1-(cyclopropylmethyl)-6-phenylazepan-2-one (131 mg, 0.51 mmol) and p-nitrophenyl chloroformate (102 mg, 0.51 mmol) in tetrahydrofuran (5 mL) at 0° C. After 0.5 h, triethylamine (0.18 mL, 1.28 mmol) and 4-(2-oxo-4-phenyl-2,3-dihydro-1H-imidazol-1-yl)piperidinium chloride (142 mg, 0.51 mmol) were added and the mixture was allowed to warm to ambient temperature. After 2 h, the mixture was concentrated. Purification by preparative reverse phase chromatography (DeltaPak C18, 15 □, 47 mm×300 mm, 65 mL/min: 5% CH3CN to 95% CH3CN over 60 min) afforded the racemic compound. The cis and trans enantiomers were both separated using a Chiralcel AD column eluting with 30% 2-propanol/hexanes→70% propanol/hexanes (0.1% diethylamine in hexanes) to give the title compound (50 mg). MS 528.3 (M+1)

Workup

  1. waitAfter 2 h
  2. concentrationthe mixture was concentrated
  3. customPurification by preparative reverse phase chromatography (DeltaPak C18, 15 □, 47 mm×300 mm, 65 mL/min: 5% CH3CN to 95% CH3CN over 60 min)
  4. customafforded the racemic compound
  5. washeluting with 30% 2-propanol/hexanes

Sources & evidence

ORD record
ord-401c32fa9e7f4cd492d0b3ee9548474a
Source dataset
uspto-grants-2009_02
Patent number
US07491713B2

Reaction notes

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