Triethylamine → N-((6S,9R)-3-cyclopropyl-6-(2,3-difluorophenyl)-6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[4,3-a]azepin-9-yl)-4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxamide

HRID 1664927Notes

Reaction equation

HRID 1664927 reaction equation
C(N(CC)CC)C.[F:8][C:9]1[C:14]([F:15])=[CH:13][CH:12]=[CH:11][C:10]=1[C@H:16]1[CH2:22][NH:21][C:20](=[N:23][NH2:24])[C@H:19]([NH:25][C:26]([N:28]2[CH2:33][CH2:32][CH:31]([N:34]3[C:42]4[C:37](=[N:38][CH:39]=[CH:40][CH:41]=4)[NH:36][C:35]3=[O:43])[CH2:30][CH2:29]2)=[O:27])[CH2:18][CH2:17]1.[CH:44]1([C:47](Cl)=O)[CH2:46][CH2:45]1>ClCCl>[CH:44]1([C:47]2[N:21]3[CH2:22][C@H:16]([C:10]4[CH:11]=[CH:12][CH:13]=[C:14]([F:15])[C:9]=4[F:8])[CH2:17][CH2:18][C@@H:19]([NH:25][C:26]([N:28]4[CH2:29][CH2:30][CH:31]([N:34]5[C:42]6[C:37](=[N:38][CH:39]=[CH:40][CH:41]=6)[NH:36][C:35]5=[O:43])[CH2:32][CH2:33]4)=[O:27])[C:20]3=[N:23][N:24]=2)[CH2:46][CH2:45]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 77637Cyclopropanecarbonyl chlorideHCID 178514346HCID 178514346, compound

Product 1

HCID 54582783N-((6S,9R)-3-cyclopropyl-6-(2,3-difluorophenyl)-6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[4,3-a]azepin-9-yl)-4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxamideYield 88.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
45 °C

Procedure

Triethylamine (20 μL, 0.142 mmol) was added to a solution of N-[(3R,6S)-6-(2,3-difluorophenyl)-2-hydrazonoazepan-3-yl]-4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxamide (59 mg, 0.118 mmol) and cyclopropanecarbonyl chloride (11 μL, 0.124 mmol) in dichloromethane (1 mL) and the mixture heated to 45° C. After 20 h, the reaction was concentrated. Saturated aqueous sodium bicarbonate 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/(10% ammonium hydroxide/methanol)] gave the title compound (57 mg). MS 549.2524 (M+1).

Workup

  1. concentrationthe reaction was concentrated
  2. additionSaturated aqueous sodium bicarbonate was added
  3. extractionthe mixture was extracted with dichloromethane (3×)
  4. dry with materialThe combined organic extracts were dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification by silica gel chromatography [100% dichloromethane→95% dichloromethane/(10% ammonium hydroxide/methanol)]

Sources & evidence

ORD record
ord-4bdf4fa224e54fc9a2c050d4986f4405
Source dataset
uspto-grants-2011_10
Patent number
US08039460B2

Reaction notes

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