N-(3-{6-[1-(4-Methoxybenzyl)-1H-pyrazol-4-yl]-1H-imidazo[1,2-b]pyrazol-1-yl}-4-methyl-phenyl)-3-(morpholin-4-yl)-5-(pentafluoro-lambda6-sulphanyl)benzamide → N-{4-Methyl-3-[6-(1H-pyrazol-4-yl)-1H-imidazo[1,2-b]pyrazol-1-yl]phenyl}-3-(morpholin-4-yl)-5-(pentafluoro-lambda6-sulphanyl)benzamide

HRID 1055704Notes

Reaction equation

HRID 1055704 reaction equation
COC1C=CC(C[N:8]2[CH:12]=[C:11]([C:13]3[CH:14]=[C:15]4[N:20]([C:21]5[CH:22]=[C:23]([NH:28][C:29](=[O:48])[C:30]6[CH:35]=[C:34]([S:36]([F:41])([F:40])([F:39])([F:38])[F:37])[CH:33]=[C:32]([N:42]7[CH2:47][CH2:46][O:45][CH2:44][CH2:43]7)[CH:31]=6)[CH:24]=[CH:25][C:26]=5[CH3:27])[CH:19]=[CH:18][N:16]4[N:17]=3)[CH:10]=[N:9]2)=CC=1>FC(F)(F)C(O)=O>[CH3:27][C:26]1[CH:25]=[CH:24][C:23]([NH:28][C:29](=[O:48])[C:30]2[CH:35]=[C:34]([S:36]([F:39])([F:37])([F:38])([F:40])[F:41])[CH:33]=[C:32]([N:42]3[CH2:47][CH2:46][O:45][CH2:44][CH2:43]3)[CH:31]=2)=[CH:22][C:21]=1[N:20]1[C:15]2[N:16]([N:17]=[C:13]([C:11]3[CH:12]=[N:8][NH:9][CH:10]=3)[CH:14]=2)[CH:18]=[CH:19]1

Participants

3

Reactant 1

HCID 89699732N-(3-{6-[1-(4-Methoxybenzyl)-1H-pyrazol-4-yl]-1H-imidazo[1,2-b]pyrazol-1-yl}-4-methyl-phenyl)-3-(morpholin-4-yl)-5-(pentafluoro-lambda6-sulphanyl)benzamide

Product 1

HCID 136630248N-{4-Methyl-3-[6-(1H-pyrazol-4-yl)-1H-imidazo[1,2-b]pyrazol-1-yl]phenyl}-3-(morpholin-4-yl)-5-(pentafluoro-lambda6-sulphanyl)benzamide

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

At 80° C., 98 mg (0.14 mmol) of the compound of Example 49A were stirred in 0.56 ml of trifluoroacetic acid for 3 h. The reaction was then concentrated, the residue was dissolved in ethyl acetate and the solution was washed with saturated sodium bicarbonate solution. The organic phase was dried over sodium sulphate, filtered and concentrated under reduced pressure. After drying of the residue under high vacuum, the crude product was purified by preparative HPLC (Method 29). The product fractions were combined and concentrated, and the residue was taken up in ethyl acetate and washed with saturated sodium bicarbonate solution. The organic phase was dried over sodium sulphate, filtered and concentrated under reduced pressure. Drying under high vacuum gave a first product fraction (39 mg). A second product fraction of a further 19 mg was obtained from the combined mixed fractions of the HPLC separation by concentrating these fractions followed by re-purification by the same method by preparative HPLC. This gave a total of 58 mg (69% of theory) of the title compound.

Workup

  1. concentrationThe reaction was then concentrated
  2. dissolutionthe residue was dissolved in ethyl acetate
  3. washthe solution was washed with saturated sodium bicarbonate solution
  4. dry with materialThe organic phase was dried over sodium sulphate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customAfter drying of the residue under high vacuum
  8. customthe crude product was purified by preparative HPLC (Method 29)
  9. concentrationconcentrated
  10. washwashed with saturated sodium bicarbonate solution
  11. dry with materialThe organic phase was dried over sodium sulphate
  12. filtrationfiltered
  13. concentrationconcentrated under reduced pressure
  14. customDrying under high vacuum
  15. customgave a first product fraction (39 mg)
  16. customA second product fraction of a further 19 mg was obtained from the
  17. additioncombined mixed
  18. customfractions of the HPLC separation
  19. concentrationby concentrating these fractions
  20. customfollowed by re-purification by the same method by preparative HPLC

Sources & evidence

ORD record
ord-b29407346f6744cca0dc8f8ef2d79c75
Source dataset
uspto-grants-2016_07
Patent number
US09394309B2

Reaction notes

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