Sodium Iodide → n-Cyclohexyl-2-(6-methyl-6-{3-[(methylsufonyl)amino]phenyl}-3-azabicyclo[3.1.0]hex-3-yl)acetamide

HRID 428869Notes

Reaction equation

HRID 428869 reaction equation
[CH3:1][C:2]1([C:8]2[CH:9]=[C:10]([NH:14][S:15]([CH3:18])(=[O:17])=[O:16])[CH:11]=[CH:12][CH:13]=2)[CH:7]2[CH:3]1[CH2:4][NH:5][CH2:6]2.C(=O)([O-])O.[Na+].Cl[CH2:25][C:26]([NH:28][CH:29]1[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]1)=[O:27].[I-].[Na+]>CN(C)C=O.O.C(OCC)C>[NH3:5].[CH:29]1([NH:28][C:26](=[O:27])[CH2:25][N:5]2[CH2:6][CH:7]3[CH:3]([C:2]3([CH3:1])[C:8]3[CH:13]=[CH:12][CH:11]=[C:10]([NH:14][S:15]([CH3:18])(=[O:17])=[O:16])[CH:9]=3)[CH2:4]2)[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]1

Participants

9

Reactant 4

HCID 5238Sodium IodideHCID 2223652-Chloro-N-cyclohexylacetamideHCID 516892Sodium BicarbonateHCID 22141143N-[3-(6-methyl-3-azabicyclo[3.1.0]hex-6-yl)phenyl)methanesulfonamide

Product 2

HCID 222AmmoniaHCID 22141352n-Cyclohexyl-2-(6-methyl-6-{3-[(methylsufonyl)amino]phenyl}-3-azabicyclo[3.1.0]hex-3-yl)acetamideYield 57.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of the hydrochloride salt of N-[3-(6-methyl-3-azabicyclo[3.1.0]hex-6-yl)phenyl]methanesulfonamide (Preparation 53, 57 mg, 0.19 mmol) in N,N-dimethylformamide (2 ml) was added sodium hydrogen carbonate (630 mg, 7.52 mmol), 2-chloro-N-cyclohexylacetamide (36 mg, 0.2 mmol) and sodium iodide (catalytic) and the reaction was heated at 50° C. for 20 h. After cooling diethyl ether (5 ml) and water (7 ml) were added and the reaction mixture was stirred vigorously for 5 min. The phases were separated and the aqueous layer was further extracted with diethyl ether (2×5 ml). The combined organic extracts were dried (Na2SO4), filtered and concentrated in vacuo. The residual oil was purified by flash column chromatography using a Sep-Pak™ cartridge packed with silica gel (5 g) eluting with dichloromethane:ethanol:0.88 ammonia solution (200:8:1) to afford the title compound as an oil (22 mg, 28%).

Workup

  1. additionwere added
  2. customThe phases were separated
  3. extractionthe aqueous layer was further extracted with diethyl ether (2×5 ml)
  4. dry with materialThe combined organic extracts were dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residual oil was purified by flash column chromatography
  8. washeluting with dichloromethane

Sources & evidence

ORD record
ord-a6d729ad0be44e8b813b00505099e9be
Source dataset
uspto-grants-2001_11
Patent number
US06313312B1

Reaction notes

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