Trifluoroacetic acid → 3-(1-Benzenesulfonyl-1H-indol-5-yl)-N-hydroxy-acrylamide

HRID 84182

반응식

HRID 84182 반응식
[NH2:1][O:2]C1CCCCO1.[C:9]1([S:15]([N:18]2[C:26]3[C:21](=[CH:22][C:23]([CH:27]=[CH:28][C:29]([OH:31])=O)=[CH:24][CH:25]=3)[CH:20]=[CH:19]2)(=[O:17])=[O:16])[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C.C(O)(C(F)(F)F)=O>CN(C=O)C.CO>[C:9]1([S:15]([N:18]2[C:26]3[C:21](=[CH:22][C:23]([CH:27]=[CH:28][C:29]([NH:1][OH:2])=[O:31])=[CH:24][CH:25]=3)[CH:20]=[CH:19]2)(=[O:17])=[O:16])[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1

참가 물질

8

반응물 5

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 2724699PyBOPHCID 5142091O-(Tetrahydropyran-2-yl)hydroxylamineHCID 674343693-[1-(Benzenesulfonyl)indol-5-YL]prop-2-enoic acid

생성물 1

HCID 760349733-(1-Benzenesulfonyl-1H-indol-5-yl)-N-hydroxy-acrylamide수율 81.4%

시약·촉매·용매 2

HCID 887Methanol용매HCID 6228Dimethylformamide용매

실험 절차

NH2OTHP (0.43 g, 3.67 mmol) was added to a solution of 8 (1.00 g, 3.05 mmol), PyBOP (1.69 g, 3.24 mmol), and triethylamine (1.02 ml, 7.33 mmol) in DMF (1.5 mL). The reaction mixture was stirred at room temperature for 3 h before it was quenched with water and extracted with EtOAc (20 mL×3). The combined organic layer was dried over anhydrous MgSO4 and concentrated under reduced pressure. The residue was purified by silica gel chromatography (CH2Cl2:CH3OH=30:1:1% NH3(aq)) to give a white solid, which was treated with TFA (6.90 ml, 92.90 mmol) in the presence of CH3OH (140 mL). The reaction mixture was stirred overnight at room temperature. Then the mixture was concentrated under reduced pressure to give a white residue, which was recrystallized by CH3OH to afford Compound 3 (0.85 g) as a red solid. 1H NMR (500 MHz, CDCl3): δ6.42 (d, J=15.8 Hz, 1H), 6.75 (d, J=3.5 Hz, 1H), 7.49-7.54 (m, 3H), 7.59-7.62 (m, 1H), 7.61 (d, J=15.5 Hz, 1H), 7.68 (d, J=3.6 Hz, 1H), 7.72 (s, 1H), 7.93 (d, J=7.7 Hz, 2H), 7.98 (d, J=8.6 Hz, 1H). MS (EI) m/z: 327 (100%), 342 (M+, 3%). HRMS (EI) for C17H14N2O4S (M+): calcd, 342.0674. found, 342.0673.

후처리

  1. customwas quenched with water
  2. extractionextracted with EtOAc (20 mL×3)
  3. dry with materialThe combined organic layer was dried over anhydrous MgSO4
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by silica gel chromatography (CH2Cl2:CH3OH=30:1:1% NH3(aq))
  6. customto give a white solid, which
  7. stirringThe reaction mixture was stirred overnight at room temperature
  8. concentrationThen the mixture was concentrated under reduced pressure
  9. customto give a white residue, which
  10. customwas recrystallized by CH3OH

출처 및 근거

ORD 기록
ord-f1d491b3e98049cebbc22fd92698416e
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08846748B2

연결된 노트

불러오는 중…