1-Bromo-2-methylbutane → 4-((3,5-dimethylisoxazol-4-yl)methoxy)-N-(5-isopropylpyridin-2-yl)-N-(2-methylbutyl)benzenesulfonamide

HRID 594172

Reaktionsgleichung

Reaktionsgleichung von HRID 594172
[CH3:1][C:2]1[C:6]([CH2:7][O:8][C:9]2[CH:14]=[CH:13][C:12]([S:15]([NH:18][C:19]3[CH:24]=[CH:23][C:22]([CH:25]([CH3:27])[CH3:26])=[CH:21][N:20]=3)(=[O:17])=[O:16])=[CH:11][CH:10]=2)=[C:5]([CH3:28])[O:4][N:3]=1.C(N=C(N(C)C)N(C)C)(C)(C)C.Br[CH2:42][CH:43]([CH3:46])[CH2:44][CH3:45]>C(#N)C>[CH3:1][C:2]1[C:6]([CH2:7][O:8][C:9]2[CH:10]=[CH:11][C:12]([S:15]([N:18]([C:19]3[CH:24]=[CH:23][C:22]([CH:25]([CH3:26])[CH3:27])=[CH:21][N:20]=3)[CH2:42][CH:43]([CH3:46])[CH2:44][CH3:45])(=[O:17])=[O:16])=[CH:13][CH:14]=2)=[C:5]([CH3:28])[O:4][N:3]=1

Komponenten

5

Edukt 3

HCID 252541-Bromo-2-methylbutaneHCID 35715812-tert-Butyl-1,1,3,3-tetramethylguanidineHCID 898760154-((3,5-dimethylisoxazol-4-yl)methoxy)-N-(5-isopropylpyridin-2-yl)benzenesulfonamide

Produkt 1

HCID 721949364-((3,5-dimethylisoxazol-4-yl)methoxy)-N-(5-isopropylpyridin-2-yl)-N-(2-methylbutyl)benzenesulfonamideAusbeute 4,6 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6342AcetonitrileLösungsmittel

Reaktionsbedingungen

Temperatur
20 °C

Versuchsvorschrift

To a solution of 4-((3,5-dimethylisoxazol-4-yl)methoxy)-N-(5-isopropylpyridin-2-yl)benzenesulfonamide (156 mg, 0.389 mmol) in acetonitrile (4 mL) stirred in air at 20° C., was added 2-(tert-butyl)-1,1,3,3-tetramethylguanidine (133 mg, 0.777 mmol). The reaction mixture was stirred at 20° C. for 1 hour, then 1-bromo-2-methylbutane (117 mg, 0.777 mmol) was added. The reaction then heated by microwaves to 150° C., for 30 minutes. After cooling the solvent was removed in vacuo and diluted with ethyl acetate. The organic phase was washed with water (5 mL), then dried using a hydrophobic frit. The solvent was removed in vacuo to give the crude product as an orange oil. Purification of the crude was attempted using flash silica (Si) chromatography (0-25% ethylacetate-cyclohexane gradient) followed by mass directed autoprep (ammonium carbonate modifier), however impurities still remained. A final purification using a silica (Si) cartridge (eluting with a gradient of 0-25% ethyl acetate-cyclohexane) provided a small amount of clean product (8.5 mg) as a colourless oil. LCMS (2 min, High pH) Rt 1.48 mins, m/z (ES+) 472 (M+H).

Aufarbeitung

  1. customThe reaction
  2. temperaturethen heated by microwaves to 150° C., for 30 minutes
  3. temperatureAfter cooling the solvent
  4. customwas removed in vacuo
  5. additiondiluted with ethyl acetate
  6. washThe organic phase was washed with water (5 mL)
  7. customdried
  8. customThe solvent was removed in vacuo
  9. customto give the crude product as an orange oil
  10. customPurification of the crude
  11. customA final purification
  12. washeluting with a gradient of 0-25% ethyl acetate-cyclohexane)

Quellen und Nachweise

ORD-Eintrag
ord-5f62b9dab19b43c6b62e1a6e2d9ad25b
Quelldatensatz
uspto-grants-2016_01
Patentnummer
US09242972B2

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