Phosgene → n-[(3r,7r)-1-(Cyclopropylmethyl)-2-oxo-7-phenylazepan-3-yl]-4-(2-oxo-4-phenyl-2,3-dihydro-1h-imidazol-1-yl)piperidine-1-carboxamide

HRID 1725657Notes

Reaction equation

HRID 1725657 reaction equation
C(N(C(C)C)CC)(C)C.[C:10](Cl)(Cl)=[O:11].[Cl-].[O:15]=[C:16]1[NH:20][C:19]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[CH:18][N:17]1[CH:27]1[CH2:32][CH2:31][NH2+:30][CH2:29][CH2:28]1.[NH2:33][C@@H:34]1[CH2:40][CH2:39][CH2:38][C@H:37]([C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)[N:36]([CH2:47][CH:48]2[CH2:50][CH2:49]2)[C:35]1=[O:51]>ClCCl>[CH:48]1([CH2:47][N:36]2[C@@H:37]([C:41]3[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=3)[CH2:38][CH2:39][CH2:40][C@@H:34]([NH:33][C:10]([N:30]3[CH2:31][CH2:32][CH:27]([N:17]4[CH:18]=[C:19]([C:21]5[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=5)[NH:20][C:16]4=[O:15])[CH2:28][CH2:29]3)=[O:11])[C:35]2=[O:51])[CH2:49][CH2:50]1

Participants

6

Reactant 4

HCID 6371PhosgeneHCID 81531Diisopropylethylamine2×HCID 58844838(3R,7R)-3-Amino-1-(cyclopropylmethyl)-7-phenylazepan-2-oneHCID 673433224-(2-oxo-4-phenyl-2,3-dihydro-1H-imidazol-1-yl)piperidinium chloride

Product 1

HCID 11466680n-[(3r,7r)-1-(Cyclopropylmethyl)-2-oxo-7-phenylazepan-3-yl]-4-(2-oxo-4-phenyl-2,3-dihydro-1h-imidazol-1-yl)piperidine-1-carboxamideYield 65.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Diisopropylethylamine (0.020 mL, 0.11 mmol) and phosgene (0.06 mL, 0.56 mmol) were added to a solution of 4-(2-oxo-4-phenyl-2,3-dihydro-1H-imidazol-1-yl)piperidinium chloride (27 mg, 0.111 mmol) in dichloromethane (1 mL) at 0° C. After 30 min, the mixture was concentrated in vacuo and azeotroped with dichloromethane (2×) to give the crude amine. Diisopropylethylamine (0.04 ml, 0.22 mmol) was added to a solution of the crude amine and (3R,7R)-3-amino-1-(cyclopropylmethyl)-7-phenylazepan-2-one (28.7 mg, 0.11 mmol) in dichloromethane (1 mL) and the mixture heated to reflux. After 15 min, the mixture was concentrated and purified by silica gel chromatography (1% methanol/dichloromethane—5% methanol/dichloromethane) gave the title compound (38 mg). MS 528.3 (M+1).

Workup

  1. concentrationthe mixture was concentrated in vacuo
  2. customazeotroped with dichloromethane (2×)
  3. customto give the crude amine
  4. temperaturethe mixture heated to reflux
  5. waitAfter 15 min
  6. concentrationthe mixture was concentrated
  7. custompurified by silica gel chromatography (1% methanol/dichloromethane—5% methanol/dichloromethane)

Sources & evidence

ORD record
ord-41494fcac4b646c5975656cafba9334e
Source dataset
uspto-grants-2009_02
Patent number
US07491713B2

Reaction notes

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