Triethylamine → N-[(3R,6S)-1-(2-Methoxyethyl)-2-oxo-6-phenylazepan-3-yl]-4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxamide

HRID 501151

Reaction equation

HRID 501151 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]=[CH:18][CH:17]=2)[CH2:12][N:11]([CH2:22][CH2:23][O:24][CH3:25])[C:10]1=[O:26].Cl[C:28](OC1C=CC([N+]([O-])=O)=CC=1)=[O:29].Cl.Cl.[O:42]=[C:43]1[NH:51][C:46]2=[N:47][CH:48]=[CH:49][CH:50]=[C:45]2[N:44]1[CH:52]1[CH2:57][CH2:56][NH:55][CH2:54][CH2:53]1.C(N(C(C)C)CC)(C)C.C(=O)([O-])[O-].[Na+].[Na+]>O1CCCC1.ClCCl>[CH3:25][O:24][CH2:23][CH2:22][N:11]1[CH2:12][C@H:13]([C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH2:14][CH2:15][C@@H:9]([NH:8][C:28]([N:55]2[CH2:56][CH2:57][CH:52]([N:44]3[C:45]4[C:46](=[N:47][CH:48]=[CH:49][CH:50]=4)[NH:51][C:43]3=[O:42])[CH2:53][CH2:54]2)=[O:29])[C:10]1=[O:26]

Participants

9

Reactant 6

HCID 8471TriethylamineHCID 10340Sodium CarbonateHCID 81531DiisopropylethylamineHCID 821294-Nitrophenyl chloroformateHCID 222931811-(piperidin-4-yl)-1H,2H,3H-imidazo[4,5-b]pyridin-2-one dihydrochlorideHCID 60037849(3R,6S)-3-Amino-1-(2-methoxyethyl)-6-phenylazepan-2-one

Product 1

HCID 11272121N-[(3R,6S)-1-(2-Methoxyethyl)-2-oxo-6-phenylazepan-3-yl]-4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxamideYield 83%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

Triethylamine (0.015 mL, 0.107 mmol) was added to a solution of (3R,6S)-3-amino-1-(2-methoxyethyl)-6-phenylazepan-2-one (28 mg, 0.107 mmol) and 4-nitrophenyl chloroformate (22 mg, 0.107 mmol) in tetrahydrofuran (2 mL) at 0° C. After 30 min, 2-oxo-1-(4-piperidinyl)-2,3-dihydro-1H-imidazo[4,5-b]pyridine dihydrochloride (37 mg, 0.128 mmol), diisopropylethylamine (0.074 mL, 0.427 mmol) and dichloromethane (2.5 mL) were added and the mixture allowed to warm to ambient temperature. After 18 h, saturated aqueous sodium carbonate was added and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium carbonate (3×), saturated brine, dried over magnesium sulfate, filtered and concentrated. Purification by silica gel chromatography (100% dichloromethane→93% dichloromethane/methanol) gave the title compound (45 mg). MS 507.2737 (M+1).

Workup

  1. waitAfter 18 h
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe organic layer was washed with saturated aqueous sodium carbonate (3×), saturated brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification by silica gel chromatography (100% dichloromethane→93% dichloromethane/methanol)

Sources & evidence

ORD record
ord-412a817b008a4fd5854ecb0ff13b9d52
Source dataset
uspto-grants-2010_08
Patent number
US07772224B2

Linked notes

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