Sodium hydride → 3-{5-[(4-Methylpiperazin-1-yl)sulfonyl]pyridin-2-yl}-1H-indol-2-ol hydrochloride

HRID 748541

반응식

HRID 748541 반응식
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][C:2]1=[O:10].[Cl:11][C:12]1[N:17]=[CH:16][C:15]([S:18]([N:21]2[CH2:26][CH2:25][N:24]([CH3:27])[CH2:23][CH2:22]2)(=[O:20])=[O:19])=[CH:14][CH:13]=1.[H-].[Na+].C(=O)([O-])O.[Na+]>CN(C)C=O>[ClH:11].[CH3:27][N:24]1[CH2:25][CH2:26][N:21]([S:18]([C:15]2[CH:14]=[CH:13][C:12]([C:3]3[C:4]4[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=4)[NH:1][C:2]=3[OH:10])=[N:17][CH:16]=2)(=[O:19])=[O:20])[CH2:22][CH2:23]1

참가 물질

6

반응물 4

HCID 24758Sodium hydrideHCID 321710OxindoleHCID 516892Sodium BicarbonateHCID 8224571-(6-Chloro-pyridine-3-sulfonyl)-4-methyl-piperazine

생성물 1

HCID 1363421233-{5-[(4-Methylpiperazin-1-yl)sulfonyl]pyridin-2-yl}-1H-indol-2-ol hydrochloride수율 37%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

Sodium hydride (46 mg, 60% dispersion in paraffin) was washed with hexane and dried in vacuo. N,N-Dimethylformamide (3 mL), oxindole (72 mg, 0.54 mmol) and 1-[(6-chloropyridin-3-yl)sulfonyl]-4-methylpiperazine (100 mg, 0.36 mmol; described in: Thunus L., Annales Pharmaceutiques Francaises 1977, 35, 197-203) were added to the sodium hydride and the reaction mixture was stirred at room temperature for 5 min. The reaction mixture was then heated for 10 min at 130° C. After cooling to room temperature, a saturated aqueous sodium hydrogen carbonate solution was added. The mixture was extracted twice with methylene chloride and the combined organic layers were dried (Na2SO4), filtrated and the solvent was removed in vacuo. The residue was purified on a silica gel column using a gradient ethyl acetate/methanol, (40:1 to 1:1), as the eluent. The product was dissolved in a mixture of methylene chloride (5 mL) and methanol (5 mL). Hydrogen chloride (3 mL, 1 M in diethyl ether) was added and stirring was continued for 10 min. The precipitate was washed with diethyl ether and dried in vacuo to give 50 mg (37% yield) of the title compound: 1H NMR (D2O, 400 MHz) δ 7.95 (m, 1 H), 7.45 (d, J=2 Hz, 1 H), 7.43 (dd, J=9, 2 Hz, 1 H), 7.23 (m, 1 H), 7.14 (d, J=9 Hz, 1 H), 7.00 (m, 2 H), 3.88 (d, J=14 Hz, 2 H), 3.60 (d, J=12 Hz, 2 H), 3.23 (m, 2 H), 2.94 (m, 2 H), 2.90 (s, 3 H); MS (ES) m/z 373 (M++1).

후처리

  1. washSodium hydride (46 mg, 60% dispersion in paraffin) was washed with hexane
  2. customdried in vacuo
  3. temperatureThe reaction mixture was then heated for 10 min at 130° C
  4. temperatureAfter cooling to room temperature
  5. extractionThe mixture was extracted twice with methylene chloride
  6. dry with materialthe combined organic layers were dried (Na2SO4)
  7. filtrationfiltrated
  8. customthe solvent was removed in vacuo
  9. customThe residue was purified on a silica gel column
  10. dissolutionThe product was dissolved in a mixture of methylene chloride (5 mL) and methanol (5 mL)
  11. additionHydrogen chloride (3 mL, 1 M in diethyl ether) was added
  12. stirringstirring
  13. waitwas continued for 10 min
  14. washThe precipitate was washed with diethyl ether
  15. customdried in vacuo

출처 및 근거

ORD 기록
ord-2ab1ab0177584427adac6d0cc22eaa69
출처 데이터셋
uspto-grants-2008_07
특허 번호
US07399780B2

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