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 1969514Notes

Reaction equation

HRID 1969514 reaction equation
[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

Participants

4

Reactant 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

Product 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-sulfonamideYield 43.7%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
70 °C

Procedure

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)+.

Workup

  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

Sources & evidence

ORD record
ord-f18b982e85ed4428bbce5e6ef3e9758e
Source dataset
uspto-grants-2013_04
Patent number
US08426411B2

Reaction notes

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