Potassium Iodide → Ammonia

HRID 1433266Notes

Reaction equation

HRID 1433266 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([C@@H:20]([O:23][Si:24]([C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:26])[CH3:25])[CH2:21]Br)=[C:13]2[C:18]=1[NH:17][C:16](=[O:19])[CH:15]=[CH:14]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.Cl.[NH2:33][CH2:34][CH2:35][C:36]1[CH:69]=[CH:68][C:39]([O:40][CH2:41][CH2:42][CH2:43][CH2:44][C:45]2[CH:50]=[CH:49][C:48]([OH:51])=[C:47]([C@@H:52]([C:62]3[CH:67]=[CH:66][CH:65]=[CH:64][CH:63]=3)[CH2:53][CH2:54][N:55]([CH:59]([CH3:61])[CH3:60])[CH:56]([CH3:58])[CH3:57])[CH:46]=2)=[CH:38][CH:37]=1.C(=O)([O-])O.[Na+].[I-].[K+].C(#N)CC>C(OCC)(=O)C>[NH3:17].[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([C@@H:20]([O:23][Si:24]([C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:26])[CH3:25])[CH2:21][NH:33][CH2:34][CH2:35][C:36]2[CH:37]=[CH:38][C:39]([O:40][CH2:41][CH2:42][CH2:43][CH2:44][C:45]3[CH:50]=[CH:49][C:48]([OH:51])=[C:47]([C@@H:52]([C:62]4[CH:63]=[CH:64][CH:65]=[CH:66][CH:67]=4)[CH2:53][CH2:54][N:55]([CH:56]([CH3:58])[CH3:57])[CH:59]([CH3:60])[CH3:61])[CH:46]=3)=[CH:68][CH:69]=2)=[C:13]2[C:18]=1[NH:17][C:16](=[O:19])[CH:15]=[CH:14]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 5

HCID 4875Potassium IodideHCID 7854PropionitrileHCID 516892Sodium Bicarbonate2×HCID 15606253(R)-8-(benzyloxy)-5-(2-bromo-1-((tert-butyldimethylsilyl)oxy)ethyl)quinolin-2(1H)-oneHCID 866164804-{4-[4-(2-Aminoethyl)phenoxy]butyl}-2-[(1R)-3-(diisopropylamino)-1-phenylpropyl]phenol bis hydrochloride salt

Product 2

HCID 222AmmoniaHCID 579331708-(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]quinolin-2(1H)-one

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

8-(benzyloxy)-5-[(1R)-2-bromo-1-{[tert-butyl(dimethyl)silyl]oxy}ethyl]quinolin-2(1H)-one (Prepared according to WO2005/092861, 530 mg, 1.1 mmol), 4-{4-[4-(2-aminoethyl)phenoxy]butyl}-2-[(1R)-3-(diisopropylamino)-1-phenylpropyl]phenol bis hydrochloride salt (Preparation 13, 650 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. 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 (100/0/0 to 94/6/0.6 by volume) to furnish the title compound as an oil, 406 mg.

Workup

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

Sources & evidence

ORD record
ord-4273ec02a0d347c9a693aa8f543baae3
Source dataset
uspto-grants-2009_11
Patent number
US07612084B2

Reaction notes

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