Potassium Iodide → (R)-6-((3-((3-(5-((2-((tert-butyldimethylsilyl)oxy)-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl)amino)pent-1-yn-1-yl)phenyl)carbamoyl)phenyl)sulfonyl)-4-((3-methoxyphenyl)amino)-8-methylquinoline-3-carboxamide

HRID 1944962Notes

Reaction equation

HRID 1944962 reaction equation
Br[CH2:2][CH2:3][CH2:4][C:5]#[C:6][C:7]1[CH:8]=[C:9]([NH:13][C:14]([C:16]2[CH:17]=[C:18]([S:22]([C:25]3[CH:26]=[C:27]4[C:32](=[C:33]([CH3:35])[CH:34]=3)[N:31]=[CH:30][C:29]([C:36]([NH2:38])=[O:37])=[C:28]4[NH:39][C:40]3[CH:45]=[CH:44][CH:43]=[C:42]([O:46][CH3:47])[CH:41]=3)(=[O:24])=[O:23])[CH:19]=[CH:20][CH:21]=2)=[O:15])[CH:10]=[CH:11][CH:12]=1.[NH2:48][CH2:49][C@@H:50]([C:59]1[CH:68]=[CH:67][C:66]([OH:69])=[C:65]2[C:60]=1[CH:61]=[CH:62][C:63](=[O:70])[NH:64]2)[O:51][Si:52]([C:55]([CH3:58])([CH3:57])[CH3:56])([CH3:54])[CH3:53].C(N(CC)C(C)C)(C)C.[I-].[K+]>CN(C=O)C>[Si:52]([O:51][C@H:50]([C:59]1[CH:68]=[CH:67][C:66]([OH:69])=[C:65]2[C:60]=1[CH:61]=[CH:62][C:63](=[O:70])[NH:64]2)[CH2:49][NH:48][CH2:2][CH2:3][CH2:4][C:5]#[C:6][C:7]1[CH:8]=[C:9]([NH:13][C:14]([C:16]2[CH:17]=[C:18]([S:22]([C:25]3[CH:26]=[C:27]4[C:32](=[C:33]([CH3:35])[CH:34]=3)[N:31]=[CH:30][C:29]([C:36]([NH2:38])=[O:37])=[C:28]4[NH:39][C:40]3[CH:45]=[CH:44][CH:43]=[C:42]([O:46][CH3:47])[CH:41]=3)(=[O:24])=[O:23])[CH:19]=[CH:20][CH:21]=2)=[O:15])[CH:10]=[CH:11][CH:12]=1)([C:55]([CH3:58])([CH3:57])[CH3:56])([CH3:54])[CH3:53]

Participants

6

Reactant 4

HCID 4875Potassium IodideHCID 81531DiisopropylethylamineHCID 59023604(R)-5-(2-Amino-1-((tert-butyldimethylsilyl)oxy)ethyl)-8-hydroxyquinolin-2(1H)-oneHCID 66988630HCID 66988630, compound

Product 1

HCID 86659120(R)-6-((3-((3-(5-((2-((tert-butyldimethylsilyl)oxy)-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl)amino)pent-1-yn-1-yl)phenyl)carbamoyl)phenyl)sulfonyl)-4-((3-methoxyphenyl)amino)-8-methylquinoline-3-carboxamideYield 61%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
55 °C

Procedure

A mixture of Intermediate 98 (0.35 g, 0.48 mmol) and Intermediate 2 (0.24 g, 0.72 mmol) in DMF (4.5 mL) was treated with N,N-diisopropylethylamine (0.25 mL) and catalytic potassium iodide (50 mg). The mixture was heated for 19 hours in a 55° C. oil bath. The mixture was concentrated under reduced pressure and purified via automated flash silica gel chromatography, using a 25 g Silicycle SiliSep flash column (dichloromethane/methanol/ammonium hydroxide). Concentration of the desired fractions under reduced pressure provided the title compound as a yellow solid (0.28 g, 61%). ES/MS calcd. for C53H57N6O8SSi+ 965.4. Found m/z=965.5 (M+H)+.

Workup

  1. concentrationThe mixture was concentrated under reduced pressure
  2. custompurified via automated flash silica gel chromatography

Sources & evidence

ORD record
ord-0dbe599fa3dc442d91aed564f8965637
Source dataset
uspto-grants-2013_03
Patent number
US08394829B2

Reaction notes

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