Sodium Bicarbonate → n-(3-{6-Methyl-3-[(e)-3-(2-quinolinyl)-2-propenoyl]-3-azabicyclo[3.1.0]hex-6-yl}phenyl)methanesulfonamide

HRID 1826509Notes

Reaction equation

HRID 1826509 reaction equation
O.O[N:3]1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[N:24]1[C:33]2[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=2)[CH:27]=[CH:26][C:25]=1/[CH:34]=[CH:35]/[C:36]([OH:38])=O.[CH3:39][C:40]1([C:46]2[CH:47]=[C:48]([NH:52][S:53]([CH3:56])(=[O:55])=[O:54])[CH:49]=[CH:50][CH:51]=2)[CH:45]2[CH:41]1[CH2:42][NH:43][CH2:44]2.C(=O)([O-])O.[Na+]>CN(C)C=O.ClCCl.O>[NH3:3].[CH3:39][C:40]1([C:46]2[CH:47]=[C:48]([NH:52][S:53]([CH3:56])(=[O:55])=[O:54])[CH:49]=[CH:50][CH:51]=2)[CH:45]2[CH:41]1[CH2:42][N:43]([C:36](=[O:38])/[CH:35]=[CH:34]/[C:25]1[CH:26]=[CH:27][C:28]3[C:33](=[CH:32][CH:31]=[CH:30][CH:29]=3)[N:24]=1)[CH2:44]2

Participants

10

Reactant 5

HCID 516892Sodium BicarbonateHCID 7129193-(2-Quinolinyl)-2-propenoic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 22141143N-[3-(6-methyl-3-azabicyclo[3.1.0]hex-6-yl)phenyl)methanesulfonamide

Product 2

HCID 222AmmoniaHCID 22141332n-(3-{6-Methyl-3-[(e)-3-(2-quinolinyl)-2-propenoyl]-3-azabicyclo[3.1.0]hex-6-yl}phenyl)methanesulfonamideYield 70%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of 1-hydroxybenzotriazole monohydrate (112 mg, 0.73 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (153 mg, 0.80 mmol) in N,N-dimethylformamide (5 ml) was added to (E)-3-(2-quinolinyl)-2-propenoic acid (M. Hamana, K. Funakoshi and Y. Kuchino, Chem. Pharm. Bull., 1974, 22, 1806; 131 mg, 0.66 mmol). After stirring at room temperature for 15 min, the mixture was added to the hydrochloride salt of N-[3-(6-methyl-3-azabicyclo[3.1.0]hex-6-yl)phenyl]methanesulfonamide (Preparation 53, 202 mg, 0.66 mmol) and sodium hydrogen carbonate (110 mg, 1.32 mmol). The reaction mixture was stirred at room temperature for overnight and then water (10 ml) and dichloromethane (5 ml) were added. The biphasic mixture was separated by filtering through a Whatman Microfiltration Device Filter Tube, and the resulting organic extract was concentrated using a stream of nitrogen to afford 400 mg of a crude dark red oil. This was purified by chromatography using a Biotage Flash 40S™ cartridge packed with silica gel (40 g) eluting with dichloromethane:ethanol:0.880 ammonia (100:2:1) to afford the title compound as a cream solid (206 mg, 70%).

Workup

  1. stirringThe reaction mixture was stirred at room temperature for overnight
  2. customThe biphasic mixture was separated
  3. filtrationby filtering through a Whatman Microfiltration Device
  4. filtrationFilter Tube
  5. extractionthe resulting organic extract
  6. concentrationwas concentrated
  7. customto afford 400 mg of a crude dark red oil
  8. customThis was purified by chromatography
  9. washeluting with dichloromethane

Sources & evidence

ORD record
ord-ff7f3d799f964165a78974576df7c4e0
Source dataset
uspto-grants-2006_05
Patent number
US07049444B2

Reaction notes

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