Potassium Iodide → Ammonia

HRID 1433264Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1433264
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C@@H:15]([O:18][Si:19]([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:21])[CH3:20])[CH2:16]Br)=[CH:11][C:10]=1[NH:26][CH:27]=[O:28])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.Cl.[NH2:31][CH2:32][CH2:33][C:34]1[CH:67]=[CH:66][C:37]([O:38][CH2:39][CH2:40][CH2:41][CH2:42][C:43]2[CH:48]=[CH:47][C:46]([OH:49])=[C:45]([C@@H:50]([C:60]3[CH:65]=[CH:64][CH:63]=[CH:62][CH:61]=3)[CH2:51][CH2:52][N:53]([CH:57]([CH3:59])[CH3:58])[CH:54]([CH3:56])[CH3:55])[CH:44]=2)=[CH:36][CH:35]=1.C(=O)([O-])O.[Na+].[I-].[K+].C(#N)CC.NCCC1C=CC(OCCCCC2C=CC(O)=C([C@@H](C3C=CC=CC=3)CCN(C(C)C)C(C)C)C=2)=CC=1>C(OCC)(=O)C>[NH3:26].[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C@@H:15]([O:18][Si:19]([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:21])[CH3:20])[CH2:16][NH:31][CH2:32][CH2:33][C:34]2[CH:35]=[CH:36][C:37]([O:38][CH2:39][CH2:40][CH2:41][CH2:42][C:43]3[CH:48]=[CH:47][C:46]([OH:49])=[C:45]([C@@H:50]([C:60]4[CH:61]=[CH:62][CH:63]=[CH:64][CH:65]=4)[CH2:51][CH2:52][N:53]([CH:54]([CH3:56])[CH3:55])[CH:57]([CH3:58])[CH3:59])[CH:44]=3)=[CH:66][CH:67]=2)=[CH:11][C:10]=1[NH:26][CH:27]=[O:28])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Komponenten

9

Edukt 6

HCID 4875Potassium IodideHCID 7854PropionitrileHCID 516892Sodium Bicarbonate2×HCID 574610672-bromo-(R)-1-tert-butyldimethylsiloxy-1-(3-formamido-4-benzyloxyphenyl)ethaneHCID 579331944-{4-[4-(2-aminoethyl)phenoxy]butyl}-2-[(1R)-3-(diisopropylamino)-1-phenylpropyl]phenolHCID 866164804-{4-[4-(2-Aminoethyl)phenoxy]butyl}-2-[(1R)-3-(diisopropylamino)-1-phenylpropyl]phenol bis hydrochloride salt

Produkt 2

HCID 222AmmoniaHCID 57933207N-{2-(benzyloxy)-5-[(1R)-1-{[tert-butyl(dimethyl)silyl]oxy}-2-({2-[4-(4-{3-[(1R)-3-(diisopropylamino)-1-phenylpropyl]-4-hydroxyphenyl}butoxy)phenyl]ethyl}amino)ethyl]phenyl}formamide

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

N-{2-(benzyloxy)-5-[(1R)-2-bromo-1-{[tert-butyl(dimethyl)silyl]oxy}ethyl]phenyl}formamide (Prepared according to US2005/215590, 500 mg, 1.1 mmol), 4-{4-[4-(2-aminoethyl)phenoxy]butyl}-2-[(1R)-3-(diisopropylamino)-1-phenylpropyl]phenol bis hydrochloride salt (Preparation 13, 745 mg, 1.3 mmol), sodium hydrogen carbonate (550 mg, 6.5 mmol) and potassium iodide (50 mg, 0.30 mmol) were added to propionitrile (8 ml) and heated to 90° C. and left to stir overnight. Further 4-{4-[4-(2-aminoethyl)phenoxy]butyl}-2-[(1R)-3-(diisopropylamino)-1-phenylpropyl]phenol (Preparation 13, 50 mg, 0.087 mmol) was then added and mixture stirred at 90° C. for further 24 hours. After cooling, ethyl acetate and saturated aqueous sodium hydrogen carbonate were added, organics separated and washed with more saturated aqueous sodium hydrogen carbonate, then brine and then dried (magnesium sulphate) and solvent removed in vacuo. The residue was purified by column chromatography on silica gel eluting with dichloromethane:methanol:880 ammonia (96:4:0.4 to 92:8:0.8 by volume) to furnish the title compound as an oil, 400 mg.

Aufarbeitung

  1. waitleft
  2. stirringmixture stirred at 90° C. for further 24 hours
  3. temperatureAfter cooling
  4. customorganics separated
  5. washwashed with more saturated aqueous sodium hydrogen carbonate
  6. dry with materialbrine and then dried (magnesium sulphate) and solvent
  7. customremoved in vacuo
  8. customThe residue was purified by column chromatography on silica gel eluting with dichloromethane

Quellen und Nachweise

ORD-Eintrag
ord-86e40f11b534413e8b0ef9e708e07b14
Quelldatensatz
uspto-grants-2009_11
Patentnummer
US07612084B2

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