Potassium Carbonate → 7-(2-{1-[2-(4-Cyanophenoxy)ethyl]-3-methylureido}ethyl)-9-oxa-3,7-diaza-bicyclo[3.3.1]nonane-3-carboxylic acid tert-butyl ester

HRID 899152Notes

Reaction equation

HRID 899152 reaction equation
[C:1]([C:3]1[CH:29]=[CH:28][C:6]([O:7][CH2:8][CH2:9][N:10]([CH2:15][CH2:16]OS(C2C=CC(C)=CC=2)(=O)=O)[C:11]([NH:13][CH3:14])=[O:12])=[CH:5][CH:4]=1)#[N:2].[C:30]([O:34][C:35]([N:37]1[CH2:44][CH:43]2[O:45][CH:39]([CH2:40][NH:41][CH2:42]2)[CH2:38]1)=[O:36])([CH3:33])([CH3:32])[CH3:31].C(=O)([O-])[O-].[K+].[K+]>C(#N)C.O>[C:30]([O:34][C:35]([N:37]1[CH2:38][CH:39]2[O:45][CH:43]([CH2:42][N:41]([CH2:16][CH2:15][N:10]([CH2:9][CH2:8][O:7][C:6]3[CH:5]=[CH:4][C:3]([C:1]#[N:2])=[CH:29][CH:28]=3)[C:11]([NH:13][CH3:14])=[O:12])[CH2:40]2)[CH2:44]1)=[O:36])([CH3:33])([CH3:31])[CH3:32]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 185404123-Boc-9-oxa-3,7-diazabicyclo[3.3.1]nonaneHCID 86616243Toluene-4-sulfonic acid 2-{1-[2-(4-cyanophenoxy)ethyl]-3-methylureido}ethyl ester

Product 1

HCID 690680227-(2-{1-[2-(4-Cyanophenoxy)ethyl]-3-methylureido}ethyl)-9-oxa-3,7-diaza-bicyclo[3.3.1]nonane-3-carboxylic acid tert-butyl esterYield 60.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
45 °C

Procedure

A mixture of toluene-4-sulfonic acid 2-{1-[2-(4-cyanophenoxy)ethyl]-3-methylureido}ethyl ester (1.35 g, 3.233 mmol; see Preparation I above), 9-oxa-3,7-diaza-bicyclo[3.3.1]nonane-3-carboxylic acid tert-butyl ester (1.48 g, 6.466 mmol; see WO 01/28992) and potassium carbonate (1.34 g, 9.7 mmol) in dry acetonitrile (15 mL) was stirred at 45° C. for 24 h. The reaction mixture was diluted with 20 mL water and extracted with ethyl acetate. The organic layer was washed with water, brine and dried over sodium sulfate. Solvent evaporation under reduced pressure followed by column chromatography over silica gel (using 2-2.5% methanol in dichloromethane) and further purification by preparative HPLC yielded 920 mg of the title compound as a white solid.

Workup

  1. extractionextracted with ethyl acetate
  2. washThe organic layer was washed with water, brine
  3. dry with materialdried over sodium sulfate
  4. customSolvent evaporation under reduced pressure
  5. customfollowed by column chromatography over silica gel (using 2-2.5% methanol in dichloromethane) and further purification by preparative HPLC

Sources & evidence

ORD record
ord-e442157e8ce74073ab671e05c8bde9ef
Source dataset
uspto-grants-2008_04
Patent number
US07354917B2

Reaction notes

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