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

Reaction equation

HRID 396095 reaction equation
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]

Participants

10

Reactant 6

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

Product 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)-methanesulfonamideYield 16%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-f7c6c72383b846d1bd2089c7476ab14e
Source dataset
uspto-grants-2003_08
Patent number
US06605618B2

Linked notes

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