Triethylamine → Tert-butyl 4-(5-(3-amino-6-(4-(isopropylsulfonyl)phenyl)pyrazin-2-yl)-4,5-dihydroisoxazol-3-yl)benzyl(methyl)carbamate

HRID 78692Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 78692
C1C(=O)N(Cl)C(=O)C1.[OH:9]/[N:10]=[CH:11]/[C:12]1[CH:17]=[CH:16][C:15]([CH2:18][N:19]([CH3:27])[C:20](=[O:26])[O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[CH:14][CH:13]=1.[CH:28]([S:31]([C:34]1[CH:39]=[CH:38][C:37]([C:40]2[N:41]=[C:42]([CH:47]=[CH2:48])[C:43]([NH2:46])=[N:44][CH:45]=2)=[CH:36][CH:35]=1)(=[O:33])=[O:32])([CH3:30])[CH3:29].CCN(CC)CC>CN(C=O)C.C(OCC)(=O)C.O>[NH2:46][C:43]1[C:42]([CH:47]2[O:9][N:10]=[C:11]([C:12]3[CH:13]=[CH:14][C:15]([CH2:18][N:19]([CH3:27])[C:20](=[O:26])[O:21][C:22]([CH3:23])([CH3:24])[CH3:25])=[CH:16][CH:17]=3)[CH2:48]2)=[N:41][C:40]([C:37]2[CH:36]=[CH:35][C:34]([S:31]([CH:28]([CH3:29])[CH3:30])(=[O:33])=[O:32])=[CH:39][CH:38]=2)=[CH:45][N:44]=1

Komponenten

8

Edukt 4

HCID 8471TriethylamineHCID 31398ChlorosuccinimideHCID 866827695-(4-(Isopropylsulfonyl)phenyl)-3-vinylpyrazin-2-amineHCID 89484205HCID 89484205, Verbindung

Produkt 1

HCID 86682770Tert-butyl 4-(5-(3-amino-6-(4-(isopropylsulfonyl)phenyl)pyrazin-2-yl)-4,5-dihydroisoxazol-3-yl)benzyl(methyl)carbamate

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
55 °C

Versuchsvorschrift

NCS (75.43 mg, 0.5649 mmol) was added to a solution of tert-butyl N-[[4-[(E)-hydroxyiminomethyl]phenyl]methyl]-N-methyl-carbamate (129.4 mg, 0.4896 mmol) in DMF (571.5 μL) and the reaction mixture heated at 55° C. for 15 min. After the reaction mixture was allowed to cool to room temperature, 5-(4-isopropylsulfonylphenyl)-3-vinyl-pyrazin-2-amine (114.3 mg, 0.3766 mmol) was added followed by the dropwsie addition of Et3N (76.22 mg, 105.0 μL, 0.7532 mmol). The reaction mixture was stirred at rt for 45 mins followed by heating to 65° C. for 1 hour. The reaction mixture was cooled to room temperature and diluted with ethyl acetate (5 mL) and water (5 mL) and the layers separated. The aqueous layer was extracted further with ethyl acetate (2×5 mL) and the combined organic extracts washed with water (3×10 mL), dried over MgSO4, and concentrated in vacuo to a solid. The residue was purified by column chromatography on silica using with 0-100% Ethylacetate/petroleum ether as elaunt to yield tert-butyl 4-(5-(3-amino-6-(4-(isopropylsulfonyl)phenyl)pyrazin-2-yl)-4,5-dihydroisoxazol-3-yl)benzyl(methyl)carbamate. LC/MS m/z 510.1 [M+1-56]+.

Aufarbeitung

  1. temperatureto cool to room temperature
  2. temperatureby heating to 65° C. for 1 hour
  3. temperatureThe reaction mixture was cooled to room temperature
  4. customthe layers separated
  5. extractionThe aqueous layer was extracted further with ethyl acetate (2×5 mL)
  6. washthe combined organic extracts washed with water (3×10 mL)
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated in vacuo to a solid
  9. customThe residue was purified by column chromatography on silica using with 0-100% Ethylacetate/petroleum ether as elaunt

Quellen und Nachweise

ORD-Eintrag
ord-012ba06a44944f05870b4991cd94a8f4
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08841450B2

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