Potassium Iodide → Ammonia

HRID 1433279Notes

Reaction equation

HRID 1433279 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:72]=[CH:71][C:37]([O:38][CH2:39][CH2:40][C:41]2[CH:42]=[CH:43][C:44]([O:63][CH2:64][C:65]3[CH:70]=[CH:69][CH:68]=[CH:67][CH:66]=3)=[C:45]([C@@H:47]([C:57]3[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=3)[CH2:48][CH2:49][N:50]([CH:54]([CH3:56])[CH3:55])[CH:51]([CH3:53])[CH3:52])[CH:46]=2)=[CH:36][CH:35]=1.[I-].[K+].C(=O)([O-])O.[Na+].C(#N)CC>C(OCC)(=O)C.O>[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][C:41]3[CH:42]=[CH:43][C:44]([O:63][CH2:64][C:65]4[CH:66]=[CH:67][CH:68]=[CH:69][CH:70]=4)=[C:45]([C@@H:47]([C:57]4[CH:58]=[CH:59][CH:60]=[CH:61][CH:62]=4)[CH2:48][CH2:49][N:50]([CH:51]([CH3:53])[CH3:52])[CH:54]([CH3:56])[CH3:55])[CH:46]=3)=[CH:71][CH:72]=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 5

HCID 4875Potassium IodideHCID 7854PropionitrileHCID 516892Sodium BicarbonateHCID 574610672-bromo-(R)-1-tert-butyldimethylsiloxy-1-(3-formamido-4-benzyloxyphenyl)ethaneHCID 86616485(3R)-3-[5-{2-[4-(2-aminoethyl)phenoxy]ethyl}-2-(benzyloxy)phenyl]-N,N-diisopropyl-3-phenylpropan-1-amine bis hydrochloride salt

Product 2

HCID 222AmmoniaHCID 57933175N-{2-(benzyloxy)-5-[(1R)-2-({2-[4-(2-{4-(benzyloxy)-3-[(1R)-3-(diisopropylamino)-1-phenylpropyl]phenyl}ethoxy)phenyl]ethyl}amino)-1-{[tert-butyl(dimethyl)silyl]oxy}ethyl]phenyl}formamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

N-{2-(benzyloxy)-5-[(1R)-2-bromo-1-{[tert-butyl(dimethyl)silyl]oxy}ethyl]phenyl}formamide (Prepared according to US2005/215590, 440 mg, 0.95 mmol) (3R)-3-[5-{2-[4-(2-aminoethyl)phenoxy]ethyl}-2-(benzyloxy)phenyl]-N,N-diisopropyl-3-phenylpropan-1-amine bis hydrochloride salt (Preparation 42, 600 mg, 0.95 mmol) potassium iodide (160 mg, 0.94 mmol), sodium hydrogen carbonate (480 mg, 5.65 mmol) were added to propionitrile (10 ml) and stirred at 100° C. under nitrogen for 24 hours. The mixture was cooled and water (75 ml) and ethyl acetate (75 ml) were added. Organics were separated and washed with brine, dried (magnesium sulphate) and the solvent removed in vacuo. The residue was purified by column chromatography on silica gel eluting with dichloromethane:methanol:880 ammonia (99/1/0.1 to 90/10/1 by volume) to furnish the title compound as a gum, 174 mg.

Workup

  1. temperatureThe mixture was cooled
  2. customOrganics were separated
  3. washwashed with brine
  4. dry with materialdried (magnesium sulphate)
  5. customthe solvent removed in vacuo
  6. customThe residue was purified by column chromatography on silica gel eluting with dichloromethane

Sources & evidence

ORD record
ord-074cbe60fc8a4abc95396fa28f06156a
Source dataset
uspto-grants-2009_11
Patent number
US07612084B2

Reaction notes

Loading…