Succinic anhydride → 4-{4-[5-amino-1-(2,6-difluoro-benzoyl)-1H-[1,2,4]triazol-3-ylamino]-benzenesulfonylamino}-4-oxo-butyric acid

HRID 2068991Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2068991
[NH2:1][C:2]1[N:6]([C:7](=[O:16])[C:8]2[C:13]([F:14])=[CH:12][CH:11]=[CH:10][C:9]=2[F:15])[N:5]=[C:4]([NH:17][C:18]2[CH:23]=[CH:22][C:21]([S:24]([NH2:27])(=[O:26])=[O:25])=[CH:20][CH:19]=2)[N:3]=1.CC(C)([O-])C.[K+].[C:34]1(=[O:40])[O:39][C:37](=[O:38])[CH2:36][CH2:35]1>C(O)(=O)C.C1COCC1>[NH2:1][C:2]1[N:6]([C:7](=[O:16])[C:8]2[C:13]([F:14])=[CH:12][CH:11]=[CH:10][C:9]=2[F:15])[N:5]=[C:4]([NH:17][C:18]2[CH:23]=[CH:22][C:21]([S:24]([NH:27][C:34](=[O:40])[CH2:35][CH2:36][C:37]([OH:39])=[O:38])(=[O:25])=[O:26])=[CH:20][CH:19]=2)[N:3]=1

Komponenten

6

Edukt 3

HCID 7922Succinic anhydrideHCID 5330790Jnj-7706621HCID 23665647Potassium tert-butoxide

Produkt 1

HCID 115984324-{4-[5-amino-1-(2,6-difluoro-benzoyl)-1H-[1,2,4]triazol-3-ylamino]-benzenesulfonylamino}-4-oxo-butyric acidAusbeute 31 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 176Acetic AcidKatalysatorHCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

To a nitrogen purged flask was added 4-[5-amino-1-(2,6-difluorobenzoyl)-1H-[1,2,4]triazol-3-ylamino]-benzenesulfonamide Compound 1a (0.10 g, 0.25 mmol) and THF (10 mL). The mixture was cooled to 0° C. and potassium tert-butoxide (0.28 mL, 1.0 M solution in THF) was added dropwise. After addition the mixture was stirred at 0° C. for 1 hr, then succinic anhydride (28 mg in 5 mL THF, 0.28 mmol) was added dropwise. The stirring was continued for 30 min, then the mixture was warmed to rt and stirred overnight. A few drops of acetic acid was added, then the mixture was concentrated. The residue was purified by flash chromatography (silica gel, CH2Cl2:MeOH/8:2) to afford the desired product (39 mg, 31%) as a white solid. 1H NMR (300 MHz, CD3OD) δ 7.70 (d, 2H), 7.63 (m, 1H), 7.42 (d, 2H), 7.15 (t, 2H), 2.41 (br s, 4H); MS (ESI) m/z: 493 (M+H)+.

Aufarbeitung

  1. additionAfter addition the mixture
  2. waitThe stirring was continued for 30 min
  3. temperaturethe mixture was warmed to rt
  4. stirringstirred overnight
  5. concentrationthe mixture was concentrated
  6. customThe residue was purified by flash chromatography (silica gel, CH2Cl2:MeOH/8:2)

Quellen und Nachweise

ORD-Eintrag
ord-d77fb4032e56417eb8a3c12adeea5a20
Quelldatensatz
uspto-grants-2012_10
Patentnummer
US08299082B2

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