Water → 4-Cyano-N-(2-{7-[2-(4-difluoromethoxy-phenyl)-ethyl]-9-oxa-3,7-diaza-bicyclo[3.3.1]non-3-yl}-ethyl)-N-methyl-benzenesulfonamide

HRID 1992400Notes

Reaction equation

HRID 1992400 reaction equation
Cl.Cl.[C:3]([C:5]1[CH:10]=[CH:9][C:8]([S:11]([N:14]([CH3:26])[CH2:15][CH2:16][N:17]2[CH2:24][CH:23]3[O:25][CH:19]([CH2:20][NH:21][CH2:22]3)[CH2:18]2)(=[O:13])=[O:12])=[CH:7][CH:6]=1)#[N:4].[F:27][CH:28]([F:43])[O:29][C:30]1[CH:35]=[CH:34][C:33]([CH2:36][CH2:37]OS(C)(=O)=O)=[CH:32][CH:31]=1.C(=O)([O-])[O-].[K+].[K+].O>C(#N)C>[C:3]([C:5]1[CH:10]=[CH:9][C:8]([S:11]([N:14]([CH2:15][CH2:16][N:17]2[CH2:24][CH:23]3[O:25][CH:19]([CH2:20][N:21]([CH2:37][CH2:36][C:33]4[CH:32]=[CH:31][C:30]([O:29][CH:28]([F:27])[F:43])=[CH:35][CH:34]=4)[CH2:22]3)[CH2:18]2)[CH3:26])(=[O:13])=[O:12])=[CH:7][CH:6]=1)#[N:4]

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 54016432Benzeneethanol, 4-(difluoromethoxy)-, 1-methanesulfonateHCID 685209314-cyano-N-methyl-N-[2-(9-oxa-3,7-diaza-bicyclo[3.3.1]non-3-yl)-ethyl]-benzenesulfonamide dihydrochloride

Product 1

HCID 685199424-Cyano-N-(2-{7-[2-(4-difluoromethoxy-phenyl)-ethyl]-9-oxa-3,7-diaza-bicyclo[3.3.1]non-3-yl}-ethyl)-N-methyl-benzenesulfonamideYield 57%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of 4-cyano-N-methyl-N-[2-(9-oxa-3,7-diaza-bicyclo[3.3.1]non-3-yl)-ethyl]-benzenesulfonamide dihydrochloride (0.169 g, 0.40 mmol, prep. I above), methanesulfonic acid 2-(4-difluoromethoxy-phenyl)-ethyl ester (0.107 g, 0.40 mmol, prep W above ), potassium carbonate (0.177 g, 1.28 mmol), and water (0.1 mL) in acetonitrile (4 mL) was heated in an oil bath (60° C.) for 20 h. Solid material was filtered off and the filtrate was loaded onto a cation-exchange column (SCX-2, Isolute™, 2 g/15 mL). The column was washed with a solution of methylene chloride/acetonitrile/methanol (2:1:1, 40 mL) and eluted with 20% methanol saturated with ammonia in methylene chloride (30 mL). The filtrate was concentrated in vacuo and the crude product was purified by chromatography on silica gel using methanol saturated with ammonia in dichloromethane eluent. Concentration in vacuo afforded 118 mg (57%) of the title compound as a solid white material.

Workup

  1. filtrationSolid material was filtered off
  2. washThe column was washed with a solution of methylene chloride/acetonitrile/methanol (2:1:1, 40 mL)
  3. washeluted with 20% methanol saturated with ammonia in methylene chloride (30 mL)
  4. concentrationThe filtrate was concentrated in vacuo
  5. customthe crude product was purified by chromatography on silica gel
  6. concentrationConcentration in vacuo

Sources & evidence

ORD record
ord-d0b7488a0a4a46ada222435267af83c7
Source dataset
uspto-grants-2010_01
Patent number
US07648985B2

Reaction notes

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