Diethyl Ether → Ammonia

HRID 1826383Notes

Reaction equation

HRID 1826383 reaction equation
Cl.[CH3:2][C:3]1([C:9]2[CH:10]=[C:11]([NH:15][S:16]([CH3:19])(=[O:18])=[O:17])[CH:12]=[CH:13][CH:14]=2)[CH:8]2[CH:4]1[CH2:5][NH:6][CH2:7]2.C(=O)([O-])O.[Na+].CS(O[CH2:30][CH2:31][C:32]1[CH:37]=[CH:36][C:35]([NH:38][S:39]([CH3:42])(=[O:41])=[O:40])=[CH:34][CH:33]=1)(=O)=O.C(OCC)C>COCCOC.O>[NH3:6].[CH3:2][C:3]1([C:9]2[CH:10]=[C:11]([NH:15][S:16]([CH3:19])(=[O:18])=[O:17])[CH:12]=[CH:13][CH:14]=2)[CH:8]2[CH:4]1[CH2:5][N:6]([CH2:30][CH2:31][C:32]1[CH:33]=[CH:34][C:35]([NH:38][S:39]([CH3:42])(=[O:40])=[O:41])=[CH:36][CH:37]=1)[CH2:7]2

Participants

8

Reactant 4

HCID 3283Diethyl EtherHCID 516892Sodium BicarbonateHCID 149859624-Methanesulphonamidophenethyl mesylateHCID 22141325N-[3-(6-methyl-3-azabicyclo[3.1.0]hex-6-yl)phenyl]methanesulfonamide hydrochloride salt

Product 2

HCID 222AmmoniaHCID 22141375N-[3-(6-methyl-3-{4-[(methylsulfonyl)amino]phenethyl}-3-azabicyclo[3.1.0]hex-6-yl)phenyl]methanesulfonamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of N-[3-(6-methyl-3-azabicyclo[3.1.0]hex-6-yl)phenyl]methanesulfonamide hydrochloride salt (Preparation 53, 100 mg, 0.33 mmol) in ethylene glycol dimethyl ether (10 ml) was added sodium hydrogen carbonate (1.5 g, 18 mmol) and 4-[(methylsulfonyl)amino]phenethyl methanesulfonate (P. E. Cross, J. E. Arrowsmith, G. N. Thomas, R. P. Dickinson, DD 281 599 A5, 97 mg, 0.33 mmol) and the reaction mixture was heated at 60° C. for 20 h. After cooling, diethyl ether (15 ml) and water (15 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 (2×10 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 (10 g) eluting with dichloromethane:ethanol:0.88 ammonia solution (200:8:1) to afford the title compound as an oil. The oil was further purified by preparative HPLC (condition 9) to give the title compound as a colourless glass (11 mg, 7%).

Workup

  1. temperatureAfter cooling
  2. customThe phases were separated
  3. extractionthe aqueous layer was further extracted with diethyl ether (2×10 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-994e2a07e6a34ca596f47d06d4b0865b
Source dataset
uspto-grants-2006_05
Patent number
US07049444B2

Reaction notes

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