Hydrochloric Acid → N-{4-Methyl-3-[6-(pyridin-3-yl)-1H-imidazo[1,2-b]pyrazol-1-yl]phenyl}-3-(pentafluoro-lambda6-sulphanyl)-5-(piperazin-1-yl)benzamide

HRID 1055714Notes

Reaction equation

HRID 1055714 reaction equation
CC1C=CC(N)=CC=1N1C2N(N=C(C3C=NC=CC=3)C=2)C=C1.C(OC(N1CCN(C2C=C(C=C(S(F)(F)(F)(F)F)C=2)C(O)=O)CC1)=O)(C)(C)C.[CH3:51][C:52]1[CH:57]=[CH:56][C:55]([NH:58][C:59]([C:61]2[CH:62]=[C:63]([N:73]3[CH2:78][CH2:77][N:76](C(OC(C)(C)C)=O)[CH2:75][CH2:74]3)[CH:64]=[C:65]([S:67]([F:72])([F:71])([F:70])([F:69])[F:68])[CH:66]=2)=[O:60])=[CH:54][C:53]=1[N:86]1[C:93]2[N:89]([N:90]=[C:91]([C:94]3[CH:95]=[N:96][CH:97]=[CH:98][CH:99]=3)[CH:92]=2)[CH:88]=[CH:87]1.Cl>O1CCOCC1.CO>[CH3:51][C:52]1[CH:57]=[CH:56][C:55]([NH:58][C:59](=[O:60])[C:61]2[CH:62]=[C:63]([N:73]3[CH2:74][CH2:75][NH:76][CH2:77][CH2:78]3)[CH:64]=[C:65]([S:67]([F:71])([F:70])([F:69])([F:72])[F:68])[CH:66]=2)=[CH:54][C:53]=1[N:86]1[C:93]2[N:89]([N:90]=[C:91]([C:94]3[CH:95]=[N:96][CH:97]=[CH:98][CH:99]=3)[CH:92]=2)[CH:88]=[CH:87]1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 86690979tert-butyl 4-[3-({4-methyl-3-[6-(pyridin-3-yl)-1H-imidazo[1,2-b]pyrazol-1-yl]phenyl}carbamoyl)-5-(pentafluoro-lambda6-sulphanyl)-phenyl]piperazine-1-carboxylateHCID 896995763-[4-(tert-Butoxycarbonyl)piperazin-1-yl]-5-(pentafluoro-lambda6-sulphanyl)benzoic acidHCID 897000234-Methyl-3-[6-(pyridin-3-yl)-1H-imidazo[1,2-b]pyrazol-1-yl]aniline

Product 1

HCID 86690978N-{4-Methyl-3-[6-(pyridin-3-yl)-1H-imidazo[1,2-b]pyrazol-1-yl]phenyl}-3-(pentafluoro-lambda6-sulphanyl)-5-(piperazin-1-yl)benzamide

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
80 °C

Procedure

120 mg (0.42 mmol) of the compound of Example 6A and 179 mg (0.42 mmol) of the compound of Example 16A were reacted and worked up analogously to the procedure of Example 16. In this manner, 260 mg (89% of theory) of the Boc-protected intermediate tert-butyl 4-[3-({4-methyl-3-[6-(pyridin-3-yl)-1H-imidazo[1,2-b]pyrazol-1-yl]phenyl}carbamoyl)-5-(pentafluoro-λ6-sulphanyl)-phenyl]piperazine-1-carboxylate were obtained. This compound was dissolved in 3 ml of 1,4-dioxane and 1 ml of methanol, 0.31 ml (1.24 mmol) of a 4 M solution of hydrogen chloride in 1,4-dioxane was added and the mixture was stirred at 80° C. for 1 h. The mixture was then concentrated under reduced pressure and the residue was purified by preparative HPLC (Method 18). The product fractions were concentrated and the residue was dissolved in ethyl acetate and washed successively with saturated potassium carbonate solution and saturated sodium chloride solution. The organic phase was dried over sodium sulphate, filtered and concentrated under reduced pressure. Drying of the residue gave 155 mg (62% of theory) of the title compound.

Workup

  1. customwere obtained
  2. concentrationThe mixture was then concentrated under reduced pressure
  3. customthe residue was purified by preparative HPLC (Method 18)
  4. concentrationThe product fractions were concentrated
  5. dissolutionthe residue was dissolved in ethyl acetate
  6. washwashed successively with saturated potassium carbonate solution and saturated sodium chloride solution
  7. dry with materialThe organic phase was dried over sodium sulphate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customDrying of the residue

Sources & evidence

ORD record
ord-ab86ac06e4c04ce5bd3d7695349ecd19
Source dataset
uspto-grants-2016_07
Patent number
US09394309B2

Reaction notes

Loading…