Water → N-[(3R,6S)-6-(2,3-Difluorophenyl)-2-thioxo-1-(2,2,2-trifluoroethyl)azepan-3-yl]-4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxamide

HRID 14397

Reaction equation

HRID 14397 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][C:25]([F:28])([F:27])[F:26])[C:10]1=[S:29].[O:30]=[C:31]1[NH:39][C:34]2=[N:35][CH:36]=[CH:37][CH:38]=[C:33]2[N:32]1[CH:40]1[CH2:45][CH2:44][N:43]([C:46](Cl)=[O:47])[CH2:42][CH2:41]1.O>ClCCl>[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][C:25]([F:27])([F:28])[F:26])[C:10](=[S:29])[C@H:9]([NH:8][C:46]([N:43]2[CH2:42][CH2:41][CH:40]([N:32]3[C:33]4[C:34](=[N:35][CH:36]=[CH:37][CH:38]=4)[NH:39][C:31]3=[O:30])[CH2:45][CH2:44]2)=[O:47])[CH2:15][CH2:14]1

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 222932214-(2-Oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carbonyl chlorideHCID 86616757(3R,6S)-3-Amino-6-(2,3-difluorophenyl)-1-(2,2,2-trifluoroethyl)azepane-2-thione

Product 1

HCID 86616758N-[(3R,6S)-6-(2,3-Difluorophenyl)-2-thioxo-1-(2,2,2-trifluoroethyl)azepan-3-yl]-4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxamideYield 55.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Triethylamine (100 μL, 0.720 mmol) was added to a solution of the bis hydrochloride salt of (3R,6S)-3-amino-6-(2,3-difluorophenyl)-1-(2,2,2-trifluoroethyl)azepane-2-thione (90 mg, 0.240 mmol) and 4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carbonyl chloride (74 mg, 0.264 mmol) in dichloromethane (10 mL) and the mixture heated to reflux. After 18 h, the reaction was allowed to cool to ambient temperature, water was added and the mixture was extracted with dichloromethane (3×). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated. Purification by silica gel chromatography (100% dichloromethane→95% dichloromethane/methanol) gave the title compound (78 mg). MS 583.2 (M+1).

Workup

  1. temperaturethe mixture heated to reflux
  2. extractionthe mixture was extracted with dichloromethane (3×)
  3. dry with materialThe combined organic extracts were dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification by silica gel chromatography (100% dichloromethane→95% dichloromethane/methanol)

Sources & evidence

ORD record
ord-aa1b893dcf154e85b3ad2cfec0553e85
Source dataset
uspto-grants-2010_06
Patent number
US07732438B2

Linked notes

Loading…