Trifluoroacetic acid → N-[5-(3,5-Dicyano-2,6-dimethyl-1,4-dihydropyridin-4-yl)-1H-indazol-3-yl]-2-methoxyethane-sulfonamide

HRID 1038406노트

반응식

HRID 1038406 반응식
[NH2:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([CH:11]3[C:16]([C:17]#[N:18])=[C:15]([CH3:19])[NH:14][C:13]([CH3:20])=[C:12]3[C:21]#[N:22])[CH:9]=2)[N:4](C(OC(C)(C)C)=O)[N:3]=1.[CH3:30][O:31][CH2:32][CH2:33][S:34](Cl)(=[O:36])=[O:35].C(N(CC)CC)C.FC(F)(F)C(O)=O>ClCCl>[C:21]([C:12]1[CH:11]([C:8]2[CH:9]=[C:10]3[C:5](=[CH:6][CH:7]=2)[NH:4][N:3]=[C:2]3[NH:1][S:34]([CH2:33][CH2:32][O:31][CH3:30])(=[O:36])=[O:35])[C:16]([C:17]#[N:18])=[C:15]([CH3:19])[NH:14][C:13]=1[CH3:20])#[N:22]

참가 물질

6

반응물 4

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 134802212-Methoxyethane-1-sulfonyl chlorideHCID 24959832tert-Butyl 3-amino-5-(3,5-dicyano-2,6-dimethyl-1,4-dihydropyridin-4-yl)-1H-indazole-1-carboxylate

생성물 1

HCID 67023863N-[5-(3,5-Dicyano-2,6-dimethyl-1,4-dihydropyridin-4-yl)-1H-indazol-3-yl]-2-methoxyethane-sulfonamide

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

To 100 mg (0.256 mmol) tert-butyl 3-amino-5-(3,5-dicyano-2,6-dimethyl-1,4-dihydropyridin-4-yl)-1H-indazole-1-carboxylate (Example 3A) in dichloromethane (4 ml) were added 123 mg (0.77 mmol) 2-methoxyethanesulfonyl chloride and 0.11 ml (0.77 mmol) triethylamine. The mixture was stirred at room temperature for 12 h and then concentrated under reduced pressure. The residue was dissolved in ethyl acetate and washed with brine. The aqueous layer was re-extracted with ethyl acetate, and the combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was dissolved in dichloromethane (4 ml), and to the solution were added 0.175 ml (2.27 mmol) trifluoroacetic acid. The mixture was stirred at room temperature for 2 h and then concentrated under reduced pressure. The residue was dissolved in ethyl acetate and washed with saturated aqueous sodium bicarbonate solution. The organic layer was separated, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by preparative RP-HPLC (acetonitrile/water gradient) to give 32 mg (30% of th.) of the title compound.

후처리

  1. concentrationconcentrated under reduced pressure
  2. dissolutionThe residue was dissolved in ethyl acetate
  3. washwashed with brine
  4. extractionThe aqueous layer was re-extracted with ethyl acetate
  5. washthe combined organic layers were washed with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. dissolutionThe residue was dissolved in dichloromethane (4 ml)
  10. stirringThe mixture was stirred at room temperature for 2 h
  11. concentrationconcentrated under reduced pressure
  12. dissolutionThe residue was dissolved in ethyl acetate
  13. washwashed with saturated aqueous sodium bicarbonate solution
  14. customThe organic layer was separated
  15. dry with materialdried over sodium sulfate
  16. filtrationfiltered
  17. concentrationconcentrated under reduced pressure
  18. customThe residue was purified by preparative RP-HPLC (acetonitrile/water gradient)

출처 및 근거

ORD 기록
ord-6756cc32cb454cada02a1a13d5491ac8
출처 데이터셋
uspto-grants-2013_10
특허 번호
US08551989B2

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