Potassium Iodide → (R)-N-(4-(5-((2-((tert-butyldimethylsilyl)oxy)-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl)amino)pent-1-yn-1-yl)phenyl)-2,2,2-trifluoroacetamide

HRID 385270Notes

Reaction equation

Br[CH2:2][CH2:3][CH2:4][C:5]#[C:6][C:7]1[CH:12]=[CH:11][C:10]([NH:13][C:14](=[O:19])[C:15]([F:18])([F:17])[F:16])=[CH:9][CH:8]=1.[NH2:20][CH2:21][C@@H:22]([C:31]1[CH:40]=[CH:39][C:38]([OH:41])=[C:37]2[C:32]=1[CH:33]=[CH:34][C:35](=[O:42])[NH:36]2)[O:23][Si:24]([C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:26])[CH3:25].C(N(CC)C(C)C)(C)C.[I-].[K+]>CN(C=O)C>[Si:24]([O:23][C@H:22]([C:31]1[CH:40]=[CH:39][C:38]([OH:41])=[C:37]2[C:32]=1[CH:33]=[CH:34][C:35](=[O:42])[NH:36]2)[CH2:21][NH:20][CH2:2][CH2:3][CH2:4][C:5]#[C:6][C:7]1[CH:12]=[CH:11][C:10]([NH:13][C:14](=[O:19])[C:15]([F:18])([F:17])[F:16])=[CH:9][CH:8]=1)([C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:26])[CH3:25]

Participants

Conditions

Temperature: 55 °C

Procedure

A mixture of Intermediate 26 (0.33 g, 1.0 mmol) and Intermediate 2 (0.40 g, 1.2 mmol) in DMF (5 mL) was treated with N,N-diisopropylethylamine (DIEA, 0.25 mL, 1.5 mmol) and catalytic potassium iodide. The mixture was heated overnight in a 55° C. oil bath. The mixture was concentrated under reduced pressure and purified via automated flash silica gel chromatography, using a 12 g Isco RediSep flash column (dichloromethane/methanol/ammonium hydroxide). Concentration of the desired fractions under reduced pressure provided the title compound (0.53 g, 90%). ES/MS calcd. for C30H37F3N3O4Si+588.3. found m/z=588.4 (M+H)+.

Workup

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

Sources & evidence

ORD record: ord-fcb9c921f2614ef5a567a2b7543c76a5
Source dataset: uspto-grants-2013_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08367829B2

Reaction notes

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