Potassium Iodide → Ammonia

HRID 1433264Notes

Reaction equation

HRID 1433264 reaction equation
[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

Participants

9

Reactant 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

Product 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

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-86e40f11b534413e8b0ef9e708e07b14
Source dataset
uspto-grants-2009_11
Patent number
US07612084B2

Reaction notes

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