Acetic Acid → N-(2-Hydroxy-5-{(1R)-1-hydroxy-2-[2-(4-(1-[4-(3-octyl-ureido)-benzenesulfonyl]-piperidin-4-ylamino}-phenyl)-ethylamino]-ethyl}-phenyl)-methanesulfonamide

HRID 396091

Reaktionsgleichung

Reaktionsgleichung von HRID 396091
CO[CH:3](OC)[CH2:4][C:5]1[CH:38]=[CH:37][C:8]([NH:9][CH:10]2[CH2:15][CH2:14][N:13]([S:16]([C:19]3[CH:24]=[CH:23][C:22]([NH:25][C:26]([NH:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH3:36])=[O:27])=[CH:21][CH:20]=3)(=[O:18])=[O:17])[CH2:12][CH2:11]2)=[CH:7][CH:6]=1.[I-].[Na+].Cl[Si](Cl)(Cl)C.C(O)(=O)C.[NH2:52][CH2:53][C@@H:54]([C:56]1[CH:57]=[CH:58][C:59]([OH:67])=[C:60]([NH:62][S:63]([CH3:66])(=[O:65])=[O:64])[CH:61]=1)[OH:55].C([BH3-])#N.[Na+]>C(#N)C.CO.ClCCl>[OH:67][C:59]1[CH:58]=[CH:57][C:56]([C@@H:54]([OH:55])[CH2:53][NH:52][CH2:3][CH2:4][C:5]2[CH:6]=[CH:7][C:8]([NH:9][CH:10]3[CH2:15][CH2:14][N:13]([S:16]([C:19]4[CH:20]=[CH:21][C:22]([NH:25][C:26]([NH:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH3:36])=[O:27])=[CH:23][CH:24]=4)(=[O:18])=[O:17])[CH2:12][CH2:11]3)=[CH:37][CH:38]=2)=[CH:61][C:60]=1[NH:62][S:63]([CH3:66])(=[O:65])=[O:64]

Komponenten

10

Edukt 6

HCID 176Acetic AcidHCID 5238Sodium IodideHCID 6399TrichloromethylsilaneHCID 5003444Sodium cyanoborohydrideHCID 12047933(R)-N-(5-(2-amino-1-hydroxyethyl)-2-hydroxyphenyl)methanesulfonamideHCID 18173588n-[4-({4-[4-(2,2-Dimethoxyethyl)anilino]-1-piperidinyl}sulfonyl)phenyl]-n'-octylurea

Produkt 1

HCID 69985573N-(2-Hydroxy-5-{(1R)-1-hydroxy-2-[2-(4-(1-[4-(3-octyl-ureido)-benzenesulfonyl]-piperidin-4-ylamino}-phenyl)-ethylamino]-ethyl}-phenyl)-methanesulfonamideAusbeute 13,9 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 887MethanolLösungsmittelHCID 6342AcetonitrileLösungsmittelHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

N-[4-({4-[4-(2,2-Dimethoxyethyl)anilino]-1-piperidinyl}sulfonyl)phenyl]-N′-octylurea (0.53 g, 0.92 mmol) was added to a pre-prepared mixture of sodium iodide (0.346 g, 2.31 mmol) and trichloro(methyl)silane (0.217 mL, 1.85 mmol) in anhydrous acetonitrile (27 mL). 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 with anhydrous magnesium sulfate, filtered and the solvent partially removed in vacuo. The aldehyde solution was used directly and treated with methanol, acetic acid (0.066 mL, 1.1 mmol), N-{5-[(1R)-2-amino-1-hydroxyethyl]-2-hydroxyphenyl}methanesulfonamide (0.227 g, 0.92 mmol) followed by sodium cyanoborohydride (0.063 g, 0.92 mmol). The reaction was stirred at ambient temperature overnight. 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 (0.097 g, 0.128 mmol).

Aufarbeitung

  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 overnight
  6. custompurified by flash chromatography on silica gel Merck-60 (eluant: 5:1 chloroform-methanol containing 1% ammonium hydroxide)

Quellen und Nachweise

ORD-Eintrag
ord-56a234160c064df9b2809e7e5dbd95e9
Quelldatensatz
uspto-grants-2003_08
Patentnummer
US06605618B2

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