Tert-Butylamine → N-{3-[4-(2-amino-pyridin-4-yl)-1-ethyl-1H-pyrazol-3-yl]-2,4-difluoro-phenyl}-2,5-difluoro-benzenesulfonamide

HRID 45900Notes

Reaction equation

HRID 45900 reaction equation
[CH2:1]([N:3]1[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][N:11]=[CH:10][CH:9]=2)[C:5]([C:14]2[C:15]([F:39])=[C:16]([N:21](COCCOC)[S:22]([C:25]3[CH:30]=[C:29]([F:31])[CH:28]=[CH:27][C:26]=3[F:32])(=[O:24])=[O:23])[CH:17]=[CH:18][C:19]=2[F:20])=[N:4]1)[CH3:2].C1C=C(Cl)C=C(C(OO)=O)C=1.C([NH2:55])(C)(C)C.FC(F)(F)C(O)=O>C(Cl)Cl>[NH2:55][C:12]1[CH:13]=[C:8]([C:6]2[C:5]([C:14]3[C:15]([F:39])=[C:16]([NH:21][S:22]([C:25]4[CH:30]=[C:29]([F:31])[CH:28]=[CH:27][C:26]=4[F:32])(=[O:24])=[O:23])[CH:17]=[CH:18][C:19]=3[F:20])=[N:4][N:3]([CH2:1][CH3:2])[CH:7]=2)[CH:9]=[CH:10][N:11]=1

Participants

6

Reactant 4

HCID 6385Tert-Butylamine2×HCID 6422Trifluoroacetic acidHCID 70297m-Chloroperbenzoic acid2×HCID 67184570N-[3-(1-ethyl-4-pyridin-4-yl-1H-pyrazol-3-yl)-2,4-difluoro-phenyl]-2,5-difluoro-N-(2-methoxy-ethoxymethyl)-benzenesulfonamide

Product 1

HCID 44622365N-{3-[4-(2-amino-pyridin-4-yl)-1-ethyl-1H-pyrazol-3-yl]-2,4-difluoro-phenyl}-2,5-difluoro-benzenesulfonamideYield 43.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

N-[3-(1-ethyl-4-pyridin-4-yl-1H-pyrazol-3-yl)-2,4-difluoro-phenyl]-2,5-difluoro-N-(2-methoxy-ethoxymethyl)-benzenesulfonamide (123 mg, 0.217 mmol) was dissolved in dry DCM, mCPBA (75 mg, 2 eq) was added and the reaction mixture was stirred at room temperature for 3 hours. A further addition of mCPBA was made (50 mg) and the mixture was stirred for 2 more hours. It was then diluted with DCM, washed with saturated aqueous NaHCO3 and brine, dried over Na2SO4 and evaporated to dryness. The crude intermediate N-oxide (130 mg) was dissolved in dry trifluoromethylbenzene (1.5 mL), the solution was cooled to 0° C. and t-butyl amine (0.118 mL 1.12 mmol, 5 eq) was added. Tosylanhydride (150 mg, 0.448 mmol, 2 eq) was then added in portions. After 1 h stirring at 0° C., further additions of t-butyl amine (0.03 mL, 1.25 eq) and tosylanhydride (40 mg, 0.5 eq) were made and the reaction mixture was stirred at 0° C. for 30 more minutes. Trifluoroacetic acid (1.5 mL) was then added and the mixture was hated to 70° C. and stirred at this temperature for 1.5 h. The solvent was evaporated and the residue taken up with DCM and water. The aqueous phase was neutralized with 32% aq. NaOH and extracted 3 times with DCM. The combined organic layers were washed with brine, dried over Na2SO4 and evaporated to dryness. The crude product was purified by chromatography on silica gel (DCM/MeOH 95:5) to give 46 mg of N-{3-[4-(2-amino-pyridin-4-yl)-1-ethyl-1H-pyrazol-3-yl]-2,4-difluoro-phenyl}-2,5-difluoro-benzenesulfonamide as a white solid.

Workup

  1. stirringthe mixture was stirred for 2 more hours
  2. washwashed with saturated aqueous NaHCO3 and brine
  3. dry with materialdried over Na2SO4
  4. customevaporated to dryness
  5. dissolutionThe crude intermediate N-oxide (130 mg) was dissolved in dry trifluoromethylbenzene (1.5 mL)
  6. temperaturethe solution was cooled to 0° C.
  7. stirringAfter 1 h stirring at 0° C.
  8. stirringthe reaction mixture was stirred at 0° C. for 30 more minutes
  9. customwas hated to 70° C.
  10. stirringstirred at this temperature for 1.5 h
  11. customThe solvent was evaporated
  12. extractionextracted 3 times with DCM
  13. washThe combined organic layers were washed with brine
  14. dry with materialdried over Na2SO4
  15. customevaporated to dryness
  16. customThe crude product was purified by chromatography on silica gel (DCM/MeOH 95:5)

Sources & evidence

ORD record
ord-0e66395dc8ca486d9b377600d34d5304
Source dataset
uspto-grants-2013_09
Patent number
US08541575B2

Reaction notes

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