Acetic Acid → N-(2-Hydroxy-5-[(1R)-1-hydroxy-2-[2-(4-[1-[4-(piperidine-1-sulfonyl)-phenyl]-piperidin-4-ylamino}-phenyl)-ethylamino]-ethyl}-phenyl)-methanesulfonamide

HRID 396095

반응식

HRID 396095 반응식
CO[CH:3](OC)[CH2:4][C:5]1[CH:10]=[CH:9][C:8]([NH:11][CH:12]2[CH2:17][CH2:16][N:15]([C:18]3[CH:23]=[CH:22][C:21]([S:24]([N:27]4[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]4)(=[O:26])=[O:25])=[CH:20][CH:19]=3)[CH2:14][CH2:13]2)=[CH:7][CH:6]=1.[I-].[Na+].Cl[Si](Cl)(Cl)C.C(O)(=O)C.[NH2:46][CH2:47][C@@H:48]([C:50]1[CH:51]=[CH:52][C:53]([OH:61])=[C:54]([NH:56][S:57]([CH3:60])(=[O:59])=[O:58])[CH:55]=1)[OH:49].C([BH3-])#N.[Na+]>C(#N)C.CO.ClCCl>[OH:61][C:53]1[CH:52]=[CH:51][C:50]([C@@H:48]([OH:49])[CH2:47][NH:46][CH2:3][CH2:4][C:5]2[CH:10]=[CH:9][C:8]([NH:11][CH:12]3[CH2:17][CH2:16][N:15]([C:18]4[CH:23]=[CH:22][C:21]([S:24]([N:27]5[CH2:28][CH2:29][CH2:30][CH2:31][CH2:32]5)(=[O:26])=[O:25])=[CH:20][CH:19]=4)[CH2:14][CH2:13]3)=[CH:7][CH:6]=2)=[CH:55][C:54]=1[NH:56][S:57]([CH3:60])(=[O:59])=[O:58]

참가 물질

10

반응물 6

HCID 176Acetic AcidHCID 5238Sodium IodideHCID 6399TrichloromethylsilaneHCID 5003444Sodium cyanoborohydrideHCID 12047933(R)-N-(5-(2-amino-1-hydroxyethyl)-2-hydroxyphenyl)methanesulfonamideHCID 18173830HCID 18173830, 화합물

생성물 1

HCID 69985927N-(2-Hydroxy-5-[(1R)-1-hydroxy-2-[2-(4-[1-[4-(piperidine-1-sulfonyl)-phenyl]-piperidin-4-ylamino}-phenyl)-ethylamino]-ethyl}-phenyl)-methanesulfonamide수율 16%

시약·촉매·용매 3

HCID 887Methanol용매HCID 6342Acetonitrile용매HCID 6344Dichloromethane용매

실험 절차

N-[4-(2,2-Dimethoxyethyl)phenyl]-1-[4-(1-piperidinylsulfonyl)phenyl]-4-piperidinamine (0.395 g, 0.81 mmol) was added to a pre-prepared mixture of sodium iodide (0.303 g, 2.02 mmol) and trichloro(methyl)silane (0.191 mL, 1.62 mmol) in anhydrous acetonitrile. The reaction was stirred at ambient temperature for 3 minutes. Dichloromethane was added and the reaction washed with 10% sodium thiosulfate solution, water and brine. The organic layer was dried with anhydrous magnesium sulfate, filtered and the solvent partially removed in vacuo. The aldehyde solution was used directly and treated with methanol, acetic acid (0.06 mL, 1.01 mmol), N-{5-[(1R)-2-amino-1-hydroxyethyl]-2-hydroxyphenyl}methanesulfonamide (0.20 g, 0.812 mmol) followed by sodium cyanoborohydride (0.056 g, 0.81 mmol). The reaction was stirred at ambient temperature for 4 hours. The reaction was taken to dryness in vacuo, adsorbed onto silica and purified by flash chromatography on silica gel Merck-60 (eluant: 10:1 chloroform-containing 1% ammonium hydroxide) to yield the title compound (0.130 mmol, 0.19 mmol).

후처리

  1. washthe reaction washed with 10% sodium thiosulfate solution, water and brine
  2. dry with materialThe organic layer was dried with anhydrous magnesium sulfate
  3. filtrationfiltered
  4. customthe solvent partially removed in vacuo
  5. stirringThe reaction was stirred at ambient temperature for 4 hours
  6. custompurified by flash chromatography on silica gel Merck-60 (eluant: 10:1 chloroform-containing 1% ammonium hydroxide)

출처 및 근거

ORD 기록
ord-f7c6c72383b846d1bd2089c7476ab14e
출처 데이터셋
uspto-grants-2003_08
특허 번호
US06605618B2

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