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

反応式

HRID 396091 の反応式
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]

参加物

10

反応物 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

生成物 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)-methanesulfonamide収率 13.9%

試薬・触媒・溶媒 3

HCID 887Methanol溶媒HCID 6342Acetonitrile溶媒HCID 6344Dichloromethane溶媒

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-56a234160c064df9b2809e7e5dbd95e9
出典データセット
uspto-grants-2003_08
特許番号
US06605618B2

関連ノート

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