Water → trans-2-(2-(6-(3,5-dimethyl-1H-1,2,4-triazol-1-yl)-2-methylpyrimidin-4-yl)cyclopropyl)quinoline

HRID 1498814Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1498814
[I-].[CH3:2][S+](C)(C)=O.[H-].[Na+].[CH3:9][C:10]1[N:14]=[C:13]([CH3:15])[N:12]([C:16]2[N:21]=[C:20]([CH3:22])[N:19]=[C:18](/[CH:23]=[CH:24]/[C:25]3[CH:34]=[CH:33][C:32]4[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=4)[N:26]=3)[CH:17]=2)[N:11]=1.O>CS(C)=O>[CH3:9][C:10]1[N:14]=[C:13]([CH3:15])[N:12]([C:16]2[N:21]=[C:20]([CH3:22])[N:19]=[C:18]([C@@H:23]3[CH2:2][C@H:24]3[C:25]3[CH:34]=[CH:33][C:32]4[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=4)[N:26]=3)[CH:17]=2)[N:11]=1

Komponenten

6

Edukt 4

HCID 962WaterHCID 24758Sodium hydrideHCID 74498Sulfoxonium, trimethyl-, iodide (1:1)HCID 86732074(E)-2-(2-(6-(3,5-dimethyl-1H-1,2,4-triazol-1-yl)-2-methylpyrimidin-4-yl)vinyl)quinoline

Produkt 1

HCID 86732075trans-2-(2-(6-(3,5-dimethyl-1H-1,2,4-triazol-1-yl)-2-methylpyrimidin-4-yl)cyclopropyl)quinoline

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 679Dimethyl SulfoxideLösungsmittel2×

Reaktionsbedingungen

Temperatur
50 °C

Versuchsvorschrift

To a solution of trimethylsulfoxonium iodide (59.0 mg, 0.268 mmol, 1.3 eq.) in anhydrous DMSO (1.5 mL) was added sodium hydride (5.4 mg, 0.227 mmol, 1.1 eq.) and the reaction was heated to 50° C. for 30 minutes. The reaction was then cooled to room temperature and a solution of (E)-2-(2-(6-(3,5-dimethyl-1H-1,2,4-triazol-1-yl)-2-methylpyrimidin-4-yl)vinyl)quinoline (1-4) (70.0 mg, 0.205 mmol, 1.0 eq.) in DMSO (1.5 mL) was added. The reaction was stirred at room temperature for 1 hour, poured into water (5.0 mL) and extracted using ethyl acetate (3×5.0 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated to dryness. The residue was purified by silica gel column chromatography (10-40% ethyl acetate in hexanes) to afford trans-2-(2-(6-(3,5-dimethyl-1H-1,2,4-triazol-1-yl)-2-methylpyrimidin-4-yl)cyclopropyl)quinoline (1-5) as an off-white solid. 1H NMR (300 MHz, CDCl3) δ 8.03 (br d, 1H, J=8.5 Hz), 7.98 (br d, 1H, J=8.4 Hz), 7.75 (br dd, 1H, J=8.0, 1.0 Hz), 7.67 (ddd, 1H, J=8.5, 7.0, 1.5 Hz), 7.60 (br s, 1H), 7.46 (ddd, 1H, J=8.0, 7.0, 1.0 Hz), 7.33 (d, 1H, J=8.5 Hz), 2.96-2.83 (m, 2H), 2.89 (s, 3H), 2.68 (s, 3H), 2.06-1.94 (m, 2H). LRMS m/z (M+H+) 357 found, 357 required. m.p. 140-141° C.

Aufarbeitung

  1. temperatureThe reaction was then cooled to room temperature
  2. extractionextracted
  3. dry with materialThe combined organic layers were dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated to dryness
  6. customThe residue was purified by silica gel column chromatography (10-40% ethyl acetate in hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-9265f5bc4bf34e9b8c63508b5a53a7a1
Quelldatensatz
uspto-grants-2015_12
Patentnummer
US09200001B2

Notizen zur Reaktion

Wird geladen…