Triethylamine → N-[(3R,6S)-6-(2,3-difluorophenyl)-1-(2-methoxyethyl)-2-oxoazepan-3-yl]-4-(2-oxo-4-phenylimidazolidin-1-yl)piperidine-1-carboxamide

HRID 1725659Notes

Reaction equation

HRID 1725659 reaction equation
C(N(CC)CC)C.[NH2:8][C@@H:9]1[CH2:15][CH2:14][C@@H:13]([C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([F:22])[C:17]=2[F:23])[CH2:12][N:11]([CH2:24][CH2:25][O:26][CH3:27])[C:10]1=[O:28].Cl[C:30](OC1C=CC([N+]([O-])=O)=CC=1)=[O:31].[C:42]1([CH:48]2[CH2:52][N:51]([CH:53]3[CH2:58][CH2:57][NH:56][CH2:55][CH2:54]3)[C:50](=[O:59])[NH:49]2)[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1>O1CCCC1>[F:23][C:17]1[C:18]([F:22])=[CH:19][CH:20]=[CH:21][C:16]=1[C@H:13]1[CH2:12][N:11]([CH2:24][CH2:25][O:26][CH3:27])[C:10](=[O:28])[C@H:9]([NH:8][C:30]([N:56]2[CH2:55][CH2:54][CH:53]([N:51]3[CH2:52][CH:48]([C:42]4[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=4)[NH:49][C:50]3=[O:59])[CH2:58][CH2:57]2)=[O:31])[CH2:15][CH2:14]1

Participants

6

Reactant 4

HCID 8471Triethylamine2×HCID 821294-Nitrophenyl chloroformateHCID 575625114-Phenyl-1-piperidin-4-yl-imidazolidin-2-oneHCID 60037873(3R,6S)-3-Amino-6-(2,3-difluorophenyl)-1-(2-methoxyethyl)azepan-2-one

Product 1

HCID 11296041N-[(3R,6S)-6-(2,3-difluorophenyl)-1-(2-methoxyethyl)-2-oxoazepan-3-yl]-4-(2-oxo-4-phenylimidazolidin-1-yl)piperidine-1-carboxamideYield 23%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Triethylamine (0.012 mL, 0.084 mmol) was added to a solution (3R,6S)-3-amino-6-(2,3-difluorophenyl)-1-(2-methoxyethyl)azepan-2-one (25 mg, 0.084 mmol) and p-nitrophenyl chloroformate (25 mg, 0.126 mmol) in tetrahydrofuran (1 mL) at 0° C. After 0.5 h, triethylamine (0.036 mL, 0.252 mmol) and 4-phenyl-1-piperidin-4-yl-imidazolidin-2-one (31 mg, 0.126 mmol) were added and the mixture was allowed to warm to ambient temperature. After 1 h, the mixture was quenched with water, extracted with dichloromethane, and washed with 1 N NaOH solution. The combined organic layer was dried over sodium sulfate, filtered, and concentrated. Purification by silica gel chromatography (0.5% methanol/dichloromethane→6% methanol/dichloromethane) gave the title compound (11 mg). MS 570.3 (M+1).

Workup

  1. waitAfter 1 h
  2. customthe mixture was quenched with water
  3. extractionextracted with dichloromethane
  4. washwashed with 1 N NaOH solution
  5. dry with materialThe combined organic layer was dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification by silica gel chromatography (0.5% methanol/dichloromethane→6% methanol/dichloromethane)

Sources & evidence

ORD record
ord-47ce62215bcb404ab2319db22b830a8a
Source dataset
uspto-grants-2009_02
Patent number
US07491713B2

Reaction notes

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