Potassium Iodide → Ammonia

HRID 1433281Notes

Reaction equation

HRID 1433281 reaction equation
Cl.Cl.[NH2:3][CH2:4][CH2:5][C:6]1[CH:44]=[CH:43][C:9]([O:10][CH2:11][CH2:12][C:13]2[CH:14]=[CH:15][C:16]([O:35][CH2:36][C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=3)=[C:17]([C@@H:19]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[CH2:20][CH2:21][N:22]([CH:26]([CH3:28])[CH3:27])[CH:23]([CH3:25])[CH3:24])[CH:18]=2)=[CH:8][CH:7]=1.[CH2:45]([O:52][C:53]1[CH:54]=[CH:55][C:56]([C@@H:64]([O:67][Si:68]([C:71]([CH3:74])([CH3:73])[CH3:72])([CH3:70])[CH3:69])[CH2:65]Br)=[C:57]2[C:62]=1[NH:61][C:60](=[O:63])[CH:59]=[CH:58]2)[C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1.[I-].[K+].C(=O)([O-])O.[Na+].C(#N)CC>C(OCC)(=O)C.O>[NH3:3].[CH2:45]([O:52][C:53]1[CH:54]=[CH:55][C:56]([C@@H:64]([O:67][Si:68]([C:71]([CH3:72])([CH3:74])[CH3:73])([CH3:70])[CH3:69])[CH2:65][NH:3][CH2:4][CH2:5][C:6]2[CH:44]=[CH:43][C:9]([O:10][CH2:11][CH2:12][C:13]3[CH:14]=[CH:15][C:16]([O:35][CH2:36][C:37]4[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=4)=[C:17]([C@@H:19]([C:29]4[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=4)[CH2:20][CH2:21][N:22]([CH:26]([CH3:28])[CH3:27])[CH:23]([CH3:25])[CH3:24])[CH:18]=3)=[CH:8][CH:7]=2)=[C:57]2[C:62]=1[NH:61][C:60](=[O:63])[CH:59]=[CH:58]2)[C:46]1[CH:47]=[CH:48][CH:49]=[CH:50][CH:51]=1

Participants

9

Reactant 5

HCID 4875Potassium IodideHCID 7854PropionitrileHCID 516892Sodium BicarbonateHCID 15606253(R)-8-(benzyloxy)-5-(2-bromo-1-((tert-butyldimethylsilyl)oxy)ethyl)quinolin-2(1H)-oneHCID 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 579332168-(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]quinolin-2(1H)-one

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

(3R)-3-[5-{2-[4-(2-aminoethyl)phenoxy]ethyl}-2-(benzyloxy)phenyl]-N,N-diisopropyl-3-phenylpropan-1-amine bis hydrochloride salt (Preparation 42, 800 mg, 1.25 mmol), 8-(benzyloxy)-5-[(1R)-2-bromo-1-{[tert-butyl(dimethyl)silyl]oxy}ethyl]quinolin-2(1H)-one (Prepared according to WO2005/092861, 615 mg, 1.25 mmol), potassium iodide (210 mg, 1.25 mmol), sodium hydrogen carbonate (630 mg, 7.5 mmol) were added to propionitrile (15 ml) and stirred at 100° C. under nitrogen overnight. The mixture was cooled and water (100 ml) and ethyl acetate (100 ml) added. Organics were separated and washed with water (100 ml) then brine (50 ml), 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 (100/0/0 to 90/10/1 by volume) to furnish the title compound as a gum, 297 mg.

Workup

  1. temperatureThe mixture was cooled
  2. customOrganics were separated
  3. washwashed with water (100 ml)
  4. dry with materialbrine (50 ml), dried (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-6386b8438267420e85e1deb139ee9ba3
Source dataset
uspto-grants-2009_11
Patent number
US07612084B2

Reaction notes

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