Hydrochloric Acid → N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)azetidine-3-carboxamide

HRID 446677

Reaktionsgleichung

Reaktionsgleichung von HRID 446677
[NH2:1][C:2]1[CH:3]=[C:4]([S:8]([NH:11][C:12]2[C:21]([NH:22][C:23]3[CH:28]=[C:27]([O:29][CH3:30])[CH:26]=[C:25]([O:31][CH3:32])[CH:24]=3)=[N:20][C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[N:13]=2)(=[O:10])=[O:9])[CH:5]=[CH:6][CH:7]=1.C(OC([N:40]1[CH2:43][CH:42]([C:44](O)=[O:45])[CH2:41]1)=O)(C)(C)C.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.O1CCOCC1>CC(N(C)C)=O>[CH3:30][O:29][C:27]1[CH:28]=[C:23]([NH:22][C:21]2[C:12]([NH:11][S:8]([C:4]3[CH:3]=[C:2]([NH:1][C:44]([CH:42]4[CH2:43][NH:40][CH2:41]4)=[O:45])[CH:7]=[CH:6][CH:5]=3)(=[O:9])=[O:10])=[N:13][C:14]3[C:19]([N:20]=2)=[CH:18][CH:17]=[CH:16][CH:15]=3)[CH:24]=[C:25]([O:31][CH3:32])[CH:26]=1

Komponenten

8

Edukt 6

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 81531DiisopropylethylamineHCID 27559811-Boc-Azetidine-3-carboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 574484483-amino-N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)benzenesulfonamide

Produkt 1

HCID 57448472N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)azetidine-3-carboxamide

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 31374DimethylacetamideLösungsmittel

Versuchsvorschrift

Into a 20 mL vial was added 3-amino-N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)benzenesulfonamide (0.24 mmol, 1 equiv), prepared using procedures similar to those described in Example 15, DMA (5 mL) and 1-(tert-butoxycarbonyl)azetidine-3-carboxylic acid (0.336 mmol, 1.4 equiv). Hunig's Base (0.792 mmol, 3.3 equiv) and HATU (0.288 mmol, 1.2 equiv) were added to the vial and the reaction mixture was then stirred at room temperature overnight. Completion of the reaction was indicated by LCMS. The solvent was removed by rotary evaporation. The crude mixture was carried forward without further purification. The residue was suspended in 5 mL ethyl acetate and chilled in an ice bath. A solution of 4 N HCl in dioxane (3 mL, 5 equiv) was added with stirring. The reaction mixture was then stirred at room temperature overnight. The solid materials were collected by filtration, washed with ethylacetate then purified further by preparative reverse-phase HPLC (ammonium acetate/ACN). A Waters Fractionlynx preparative reverse-phase HPLC; equipped with a Waters SunFire Prep C18, OCD 5 μM, 30×70 mm column and running a 5-100% gradient with a binary solvent system of 25 mM ammonium acetate in water/acetonitrile; was used to carry out the purification. N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)azetidine-3-carboxamide was obtained (26 mg, 20%). 1H-NMR (400 MHz, d6-DMSO): 10.26 (s, 1H), 8.81 (s, 1H), 8.25 (t, 8.14 (s, 1H), 7.74 (d, 1H), 7.69 (d, 1H), 7.41-7.39 (m, 1H), 7.36 (d, 1H), 7.32 (d, 2H), 7.30-7.28 (dd, 1H), 7.14-7.11 (m, 2H), 6.14 (t, 1H), 4.09 (d, 4H), 3.78 (s, 6H); MS (EI) m/z C26H26N6O5S: 535.6 (MH+).

Aufarbeitung

  1. customprepared
  2. customThe solvent was removed by rotary evaporation
  3. customThe crude mixture was carried forward without further purification
  4. temperaturechilled in an ice bath
  5. stirringwith stirring
  6. stirringThe reaction mixture was then stirred at room temperature overnight
  7. filtrationThe solid materials were collected by filtration
  8. washwashed with ethylacetate
  9. customthen purified further by preparative reverse-phase HPLC (ammonium acetate/ACN)
  10. customequipped with a Waters SunFire Prep C18, OCD 5 μM, 30×70 mm column
  11. customthe purification

Quellen und Nachweise

ORD-Eintrag
ord-9faeaa2905c04eb3afd2a734c1b3b4c3
Quelldatensatz
uspto-grants-2013_07
Patentnummer
US08481001B2

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