Acetic Acid → 4-[4-(4-(2-[(2R)-2-Hydroxy-2-(4-hydroxy-3-methanesulfonylamino-phenyl)-ethylamino]-ethyl}-phenylamino)-piperidine-1-carbonyl]-benzoic acid

HRID 396082

반응식

HRID 396082 반응식
CO[CH:3](OC)[CH2:4][C:5]1[CH:29]=[CH:28][C:8]([NH:9][CH:10]2[CH2:15][CH2:14][N:13]([C:16]([C:18]3[CH:27]=[CH:26][C:21]([C:22]([O:24]C)=[O:23])=[CH:20][CH:19]=3)=[O:17])[CH2:12][CH2:11]2)=[CH:7][CH:6]=1.[I-].[Na+].Cl[Si](Cl)(Cl)C.C(O)(=O)C.[NH2:43][CH2:44][C@@H:45]([C:47]1[CH:48]=[CH:49][C:50]([OH:58])=[C:51]([NH:53][S:54]([CH3:57])(=[O:56])=[O:55])[CH:52]=1)[OH:46].C([BH3-])#N.[Na+]>C(#N)C.CO.ClCCl>[OH:46][C@H:45]([C:47]1[CH:48]=[CH:49][C:50]([OH:58])=[C:51]([NH:53][S:54]([CH3:57])(=[O:56])=[O:55])[CH:52]=1)[CH2:44][NH:43][CH2:3][CH2:4][C:5]1[CH:29]=[CH:28][C:8]([NH:9][CH:10]2[CH2:11][CH2:12][N:13]([C:16]([C:18]3[CH:27]=[CH:26][C:21]([C:22]([OH:24])=[O:23])=[CH:20][CH:19]=3)=[O:17])[CH2:14][CH2:15]2)=[CH:7][CH:6]=1

참가 물질

10

반응물 6

HCID 176Acetic AcidHCID 5238Sodium IodideHCID 6399TrichloromethylsilaneHCID 5003444Sodium cyanoborohydrideHCID 12047933(R)-N-(5-(2-amino-1-hydroxyethyl)-2-hydroxyphenyl)methanesulfonamideHCID 18173962HCID 18173962, 화합물

생성물 1

HCID 699855594-[4-(4-(2-[(2R)-2-Hydroxy-2-(4-hydroxy-3-methanesulfonylamino-phenyl)-ethylamino]-ethyl}-phenylamino)-piperidine-1-carbonyl]-benzoic acid수율 40.3%

시약·촉매·용매 3

HCID 887Methanol용매HCID 6342Acetonitrile용매HCID 6344Dichloromethane용매

실험 절차

Methyl 4-({4-[4-(2,2-dimethoxyethyl)anilino]-1-piperidinyl}carbonyl)benzoate (0.30 g, 0.703 mmol) was added to a pre-prepared mixture of sodium iodide (0.264 g, 1.76 mmol) and trichloro(methyl)silane (0.166 mL, 1.4 mmol) in anhydrous acetonitrile. The reaction was stirred at ambient temperature for 10 minutes. Dichloromethane was added and the reaction washed with 10% sodium thiosulfate solution, water and brine. The organic layer was dried over anhydrous magnesium sulfate, filtered and the solvent partially removed under vacuo. The aldehyde solution was used directly and treated with methanol (17 mL), acetic acid (0.043 mL, 0.75 mmol), N-(5-[(1R)-2-amino-1-hydroxyethyl]-2-hydroxyphenyl)methanesulfonamide (0.127 g, 0.516 mmol) followed by sodium cyanoborohydride (0.048 g, 0.764 mmol). The reaction was taken to dryness in vacuo, adsorbed onto silica and purified by flash chromatography on silica gel Merck-60 (eluant: 5:1 chloroform-methanol containing 1% ammonium hydroxide) to yield the title compound (0.127 g, 0.208 mmol).

후처리

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

출처 및 근거

ORD 기록
ord-4e95f61aac3c40dab9a622bca3acc798
출처 데이터셋
uspto-grants-2003_08
특허 번호
US06605618B2

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