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Methyl iodide → N-(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)phenyl)-N-methyl cyclopropane sulfonamide

HRID 2405561
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 2405561
[F:1][C:2]1[C:3]([NH:16][C:17]2[CH:22]=[CH:21][C:20]([I:23])=[CH:19][C:18]=2[F:24])=[C:4]([NH:9][S:10]([CH:13]2[CH2:15][CH2:14]2)(=[O:12])=[O:11])[CH:5]=[CH:6][C:7]=1[F:8].[Li+].[CH3:26][Si]([N-][Si](C)(C)C)(C)C.CI>C1COCC1>[F:1][C:2]1[C:3]([NH:16][C:17]2[CH:22]=[CH:21][C:20]([I:23])=[CH:19][C:18]=2[F:24])=[C:4]([N:9]([CH3:26])[S:10]([CH:13]2[CH2:14][CH2:15]2)(=[O:12])=[O:11])[CH:5]=[CH:6][C:7]=1[F:8]
KomponentenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

5

Edukt 3

HCID 6328Methyl iodideHCID 2733832Lithium hexamethyldisilazaneHCID 15602695N-(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)phenyl)cyclopropanesulfonamide

Produkt 1

HCID 53492153N-(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)phenyl)-N-methyl cyclopropane sulfonamide

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028Tetrahydrofuran
Lösungsmittel

Versuchsvorschrift

To a solution of N-(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)phenyl)cyclopropane-sulfonamide (see Example 2) (283.9 mg, 0.61 mmol) in 3 ml anhydrous THF was added at −78° C. a 1M solution of LHMDS (0.6 ml, 0.6 mol) and the solution was stirred for 10 min at this temperature. Then, methyl iodide (0.8 ml, 1.824 g, 12.9 mmol) was added and the mixture was warmed to room temperature and stirred for 7 h. The solvent was removed and the residue extracted using EtOAc and brine. The organic fractions were dried using Na2SO4 and the solvent was removed. The obtained crude product was purified using flash-column chromatography (Si, EtOAc/Hexanes 1:2, Rf=0.45). Yield: 205 mg, 70%). 1H-NMR (500 MHz, CDCl3): δ=7.41-7.39 (d, 1H, J=10 Hz), 7.30-7.29 (d, 1H, J=8.0 Hz), 7.23-7.20 (m, 1H), 6.98-6.93 (q, 1H, J=8.5 Hz), 6.60 (s, 1H, br), 6.51-6.47 (m, 1H), 3.23 (s, 3H), 2.46-2.42 (m, 1H), 1.19-1.16 (m, 2H), 1.04-1.02 (m, 2H); m/z=481 [M−1]−.

Aufarbeitung

  1. stirringstirred for 7 h
  2. customThe solvent was removed
  3. extractionthe residue extracted
  4. customThe organic fractions were dried
  5. customthe solvent was removed
  6. customThe obtained crude product
  7. customwas purified

Quellen und Nachweise

ORD-Eintrag
ord-2418bae1dee74d5f99089ebdec44612a
Quelldatensatz
uspto-grants-2014_08
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08808742B2

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