Reaktion #1115210

Reaktionsgleichung

MeZnCl

(S)-6-(4-bromo-3-cyano-1-cyclobutyl-6 (difluoromethoxy)-5-fluoro-1H-indol-2-yl)-N-(1,1,1-trifluoropropan-2-yl)pyridine-3-sulfonamide

HCl

→

(S)-6-(3-cyano-1-cyclobutyl-6 (difluoromethoxy)-5-fluoro-4-methyl-1H-indol-2-yl)-N-(1,1,1-trifluoropropan-2-yl)pyridine-3-sulfonamide

Ausbeute 65.0%

Lösungsmittel

THF

Reaktionsbedingungen

Aufarbeitung

1. 1
   ExtraktionThis was extracted with ethyl acetate
2. 2
   Waschenthe organic layer was washed with brine
3. 3
   TrocknenThe organic layer was dried over MgSO4
4. 4
   Filtrationfiltered
5. 5
   Einengenthe filtrate was concentrated under vacuum
6. 6
   SonstigePurification by silica gel chromatography (20% ethyl acetate in hexanes)
7. 7
   Waschenby washing with hexanes/ether (1:1)

Vorschrift

A solution of MeZnCl (2 M in THF, 370 μL, 0.74 mmol) was added to a mixture of (S)-6-(4-bromo-3-cyano-1-cyclobutyl-6 (difluoromethoxy)-5-fluoro-1H-indol-2-yl)-N-(1,1,1-trifluoropropan-2-yl)pyridine-3-sulfonamide (200 mg, 0.33 mmol), Pd(dppf)Cl2 (25 mg, 0.034 mmol), and THF (1.2 mL). This was heated at 40° C. for 25 hours. The reaction mixture was then poured onto aq. HCl. This was extracted with ethyl acetate and the organic layer was washed with brine. The organic layer was dried over MgSO4 and filtered, and the filtrate was concentrated under vacuum. Purification by silica gel chromatography (20% ethyl acetate in hexanes), followed by washing with hexanes/ether (1:1) yielded (S)-6-(3-cyano-1-cyclobutyl-6 (difluoromethoxy)-5-fluoro-4-methyl-1H-indol-2-yl)-N-(1,1,1-trifluoropropan-2-yl)pyridine-3-sulfonamide (117 mg, 65%) as a white solid. Melting point: 182-186° C.; MS m/z 547.0 M+H+; 1H NMR (CDCl3, 500 MHz): δ 9.22 (d, 1H, J=2 Hz), 8.35 (dd, 2H, J=8.5 Hz, 2 Hz), 8.02 (d, 1H, 8.5 Hz), 7.40 (d, 1H, J=6.5 Hz), 6.62 (t, 1H, J=75 Hz), 5.26 (pentet, 1H, J=8.5 Hz), 4.95 (d, 1H, J=9.5 Hz), 4.16 (m, 1H), 2.75 (d, 3H, J=2.0 Hz), 2.47 (m, 2H), 2.38 (m, 2H), 1.87 (m, 2H), 1.47 (d, 3H, J=7 Hz).

Quelle