Triethylamine → N-[(3R,6S)-6-(2,3-difluorophenyl)-7-(hydroxymethyl)-2-oxoazepan-3-yl]-4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxamide

HRID 271961Notes

Reaction equation

HRID 271961 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])[CH:12]([CH2:24][OH:25])[NH:11][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>O1CCCC1.C(Cl)(Cl)Cl>[F:23][C:17]1[C:18]([F:22])=[CH:19][CH:20]=[CH:21][C:16]=1[C@H:13]1[CH:12]([CH2:24][OH:25])[NH:11][C:10](=[O:26])[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])[CH2:15][CH2:14]1

Participants

7

Reactant 4

HCID 8471Triethylamine2×HCID 821294-Nitrophenyl chloroformateHCID 222931811-(piperidin-4-yl)-1H,2H,3H-imidazo[4,5-b]pyridin-2-one dihydrochlorideHCID 66939139HCID 66939139, compound

Product 1

HCID 60037851N-[(3R,6S)-6-(2,3-difluorophenyl)-7-(hydroxymethyl)-2-oxoazepan-3-yl]-4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxamideYield 15.7%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 8028TetrahydrofuranSolvent

Procedure

Triethylamine (0.68 mL, 0.49 mmol) was added to a solution of (3R,6S)-3-amino-6-(2,3-difluorophenyl)-7-(hydroxymethyl)azepan-2-one (57 mg, 0.21 mmol) and 4-nitrophenyl chloroformate (47 mg, 0.23 mmol) in tetrahydrofuran (10 mL) at 0° C. After 30 min, 2-oxo-1-(4-piperidinyl)-2,3-dihydro-1H-imidazo[4,5-b]pyridine dihydrochloride (98 mg, 0.34 mmol), triethylamine (0.84 mmol) and chloroform (10 mL) were added and the mixture allowed to warm to ambient temperature. The reaction was stirred overnight, concentrated, diluted with saturated aqueous sodium bicarbonate and extracted with dichloromethane (2×). The organic layer was washed with water, saturated brine, dried over magnesium sulfate, filtered and concentrated. Purification by silica gel chromatography (1%→12% methanol/dichloromethane) gave the title compound (17 mg). MS 515.2203 (M+1).

Workup

  1. concentrationconcentrated
  2. additiondiluted with saturated aqueous sodium bicarbonate
  3. extractionextracted with dichloromethane (2×)
  4. washThe organic layer was washed with water, saturated brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification by silica gel chromatography (1%→12% methanol/dichloromethane)

Sources & evidence

ORD record
ord-1f12bf2755354718803a873a7f1701be
Source dataset
uspto-grants-2008_11
Patent number
US07452903B2

Reaction notes

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