4-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)bicyclo[2.2.2]octan-1-amine → 3,3-difluoro-N-(4-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)bicyclo[2.2.2]octan-1-yl)azetidine-1-sulfonamide

HRID 1969514Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1969514
[S:1]([N:11]1[C:15]2[N:16]=[CH:17][C:18]3[N:19]([C:20]([C:23]45[CH2:30][CH2:29][C:26]([NH2:31])([CH2:27][CH2:28]4)[CH2:25][CH2:24]5)=[N:21][N:22]=3)[C:14]=2[CH:13]=[CH:12]1)([C:4]1[CH:10]=[CH:9][C:7]([CH3:8])=[CH:6][CH:5]=1)(=[O:3])=[O:2].FC(F)(F)S([O-])(=O)=O.[F:40][C:41]1([F:54])[CH2:44][N:43]([S:45](N2C=C[N+](C)=C2)(=[O:47])=[O:46])[CH2:42]1>CC#N>[F:40][C:41]1([F:54])[CH2:44][N:43]([S:45]([NH:31][C:26]23[CH2:29][CH2:30][C:23]([C:20]4[N:19]5[C:14]6[CH:13]=[CH:12][N:11]([S:1]([C:4]7[CH:10]=[CH:9][C:7]([CH3:8])=[CH:6][CH:5]=7)(=[O:3])=[O:2])[C:15]=6[N:16]=[CH:17][C:18]5=[N:22][N:21]=4)([CH2:28][CH2:27]2)[CH2:24][CH2:25]3)(=[O:47])=[O:46])[CH2:42]1

Komponenten

4

Edukt 2

HCID 580097794-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)bicyclo[2.2.2]octan-1-amineHCID 866604301-(3,3-difluoroazetidin-1-ylsulfonyl)-3-methyl-1H-imidazol-3-ium trifluoromethanesulfonate

Produkt 1

HCID 672170773,3-difluoro-N-(4-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)bicyclo[2.2.2]octan-1-yl)azetidine-1-sulfonamideAusbeute 43,7 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6342AcetonitrileLösungsmittel

Reaktionsbedingungen

Temperatur
70 °C

Versuchsvorschrift

To a solution of 4-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)bicyclo[2.2.2]-octan-1-amine (0.20 g, 0.46 mmol, Example #9, Step F) in MeCN (5 mL) was added 1-(3,3-difluoroazetidin-1-ylsulfonyl)-3-methyl-1H-imidazol-3-ium trifluoromethanesulfonate (0.19 g, 0.50 mmol). The reaction mixture was heated to about 70° C. for about 24 h. The solvent was removed under reduced pressure. The residue was partitioned between EtOAc (30 mL) and water (10 mL). The layers were separated and the organic layer was washed with water (10 mL) and brine (2×10 mL), dried over anhydrous MgSO4, filtered, and the solvent was removed under reduced pressure. The crude material was purified by flash chromatography on silica gel eluting with a gradient of 0-10% MeOH in DCM to give 3,3-difluoro-N-(4-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)bicyclo[2.2.2]octan-1-yl)azetidine-1-sulfonamide (0.119 g, 38%): LC/MS (Table 1, Method a) Rt=2.32 min; MS m/z 592 (M+H)+.

Aufarbeitung

  1. customThe solvent was removed under reduced pressure
  2. customThe residue was partitioned between EtOAc (30 mL) and water (10 mL)
  3. customThe layers were separated
  4. washthe organic layer was washed with water (10 mL) and brine (2×10 mL)
  5. dry with materialdried over anhydrous MgSO4
  6. filtrationfiltered
  7. customthe solvent was removed under reduced pressure
  8. customThe crude material was purified by flash chromatography on silica gel eluting with a gradient of 0-10% MeOH in DCM

Quellen und Nachweise

ORD-Eintrag
ord-f18b982e85ed4428bbce5e6ef3e9758e
Quelldatensatz
uspto-grants-2013_04
Patentnummer
US08426411B2

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