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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 899152
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HRID 899152 반응식
[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]
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참가 물질

6

반응물 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

생성물 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 ester수율 60.1%

시약·촉매·용매 2

HCID 962
Water
용매
HCID 6342Acetonitrile용매

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온도
45 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-e442157e8ce74073ab671e05c8bde9ef
출처 데이터셋
uspto-grants-2008_04
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07354917B2

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