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

HRID 1944922Notes

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.[Si:20]([O:27][C@H:28]([C:32]1[CH:41]=[CH:40][C:39]([OH:42])=[C:38]2[C:33]=1[CH:34]=[CH:35][C:36](=[O:43])[NH:37]2)[CH2:29][NH:30][CH3:31])([C:23]([CH3:26])([CH3:25])[CH3:24])([CH3:22])[CH3:21].C(N(CC)C(C)C)(C)C>CN(C=O)C.[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[Si:20]([O:27][C@H:28]([C:32]1[CH:41]=[CH:40][C:39]([OH:42])=[C:38]2[C:33]=1[CH:34]=[CH:35][C:36](=[O:43])[NH:37]2)[CH2:29][N:30]([CH3:31])[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:23]([CH3:25])([CH3:26])[CH3:24])([CH3:22])[CH3:21]

Participants

Conditions

Temperature: 55 °C

Procedure

A mixture of Intermediate 40 (0.30 g, 0.90 mmol) and Intermediate 4 (375 mg, 1.1 mmol) in DMF (5 mL) was treated with N,N-diisopropylethylamine (0.47 mL, 2.7 mmol) and catalytic tetra-n-butylammonium iodide (100 mg). The mixture was heated for 3 days 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 Silicycle SiliSep flash column (dichloromethane/methanol/ammonium hydroxide). Concentration of the desired fractions under reduced pressure provided the title compound. ES/MS calcd. for C31H39F3N3O4Si+ 602.3. Found m/z=602.4 (M+H)+.

Workup

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

Sources & evidence

ORD record: ord-8a67a7e4f8a84bc58d5953bf0a6e0ceb
Source dataset: uspto-grants-2013_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08394829B2

Reaction notes

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