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

HRID 899125
Notes
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Reaction equation

HRID 899125 reaction equation
[C:1]([C:3]1[CH:28]=[CH:27][C:6]([O:7][CH2:8][CH2:9][N:10]([CH2:14][CH2:15]OS(C2C=CC(C)=CC=2)(=O)=O)[C:11]([NH2:13])=[O:12])=[CH:5][CH:4]=1)#[N:2].[C:29]([O:33][C:34]([N:36]1[CH2:43][CH:42]2[O:44][CH:38]([CH2:39][NH:40][CH2:41]2)[CH2:37]1)=[O:35])([CH3:32])([CH3:31])[CH3:30].C([O-])([O-])=O.[K+].[K+].[Br-].[Li+]>C(#N)C>[C:29]([O:33][C:34]([N:36]1[CH2:37][CH:38]2[O:44][CH:42]([CH2:41][N:40]([CH2:15][CH2:14][N:10]([CH2:9][CH2:8][O:7][C:6]3[CH:5]=[CH:4][C:3]([C:1]#[N:2])=[CH:28][CH:27]=3)[C:11]([NH2:13])=[O:12])[CH2:39]2)[CH2:43]1)=[O:35])([CH3:32])([CH3:30])[CH3:31]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 82050Lithium BromideHCID 185404123-Boc-9-oxa-3,7-diazabicyclo[3.3.1]nonaneHCID 86616242Toluene-4-sulfonic acid 2-{1-[2-(4-cyanophenoxy)ethyl]ureido}ethyl ester

Product 1

HCID 690740097-(2-{1-[2-(4-Cyanophenoxy)ethyl]ureido}ethyl)-9-oxa-3,7-diazabicyclo-[3.3.1]nonane-3-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
40 °C

Procedure

A mixture of toluene-4-sulfonic acid 2-{1-[2-(4-cyanophenoxy)ethyl]-ureido}ethyl ester (15 g, 0.0372 mol, 1.0 eq.; see Preparation D above), 9-oxa-3,7-diaza-bicyclo[3.3.1]nonane-3-carboxylic acid tert-butyl ester (8.525 g, 0.0372 mol, 1.0 eq.; see WO 01/28992), fused K2CO3 (7.7 g, 0.0558 mol, 1.5 eq.) and lithium bromide (9.6 g, 0.1116 mol, 3.0 eq.) in dry acetonitrile (350 mL) was heated to 40° C. under N2 for 4 days. The reaction was cooled to rt, filtered and the filtrate was concentrated under reduced pressure. The resulting residue was purified by column chromatography over silica gel, using 3% methanol and DCM as eluent, to yield the sub-title compound as a white solid. Yield: 7 g, 40.9%.

Workup

  1. temperatureThe reaction was cooled to rt
  2. filtrationfiltered
  3. concentrationthe filtrate was concentrated under reduced pressure
  4. customThe resulting residue was purified by column chromatography over silica gel

Sources & evidence

ORD record
ord-c71c1595f5084081b31806ce941006da
Source dataset
uspto-grants-2008_04
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07354917B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes