Acetic Acid → 4-[4-(4-[2-[(2R)-2-Hydroxy-2-(4-hydroxy-3-methanesulfonylamino-phenyl)-ethylamino]-ethyl)-phenylamino)-piperidin-1-yl]-benzoic acid ethyl ester

HRID 1281625

反応式

HRID 1281625 の反応式
CO[CH:3](OC)[C:4]1[CH:27]=[CH:26][C:7]([NH:8][CH:9]2[CH2:14][CH2:13][N:12]([C:15]3[CH:25]=[CH:24]C(C(OCC)=O)=[CH:17][CH:16]=3)[CH2:11][CH2:10]2)=[CH:6][CH:5]=1.[I-].[Na+].Cl[Si](Cl)(Cl)C.[C:37](O)(=O)C.[NH2:41][CH2:42][C@@H:43]([C:45]1[CH:46]=[CH:47][C:48]([OH:56])=[C:49]([NH:51][S:52]([CH3:55])(=[O:54])=[O:53])[CH:50]=1)[OH:44].C([BH3-])#N.[Na+].Cl.[C:62]([O:65][CH2:66][CH3:67])(=[O:64])[CH3:63]>C(#N)C.O1CCCC1.CO.ClCCl>[CH2:66]([O:65][C:62](=[O:64])[C:63]1[CH:17]=[CH:16][C:15]([N:12]2[CH2:11][CH2:10][CH:9]([NH:8][C:7]3[CH:6]=[CH:5][C:4]([CH2:3][CH2:37][NH:41][CH2:42][C@H:43]([OH:44])[C:45]4[CH:46]=[CH:47][C:48]([OH:56])=[C:49]([NH:51][S:52]([CH3:55])(=[O:54])=[O:53])[CH:50]=4)=[CH:27][CH:26]=3)[CH2:14][CH2:13]2)=[CH:25][CH:24]=1)[CH3:67]

参加物

13

反応物 8

HCID 176Acetic AcidHCID 313Hydrochloric AcidHCID 5238Sodium IodideHCID 6399TrichloromethylsilaneHCID 8857Ethyl AcetateHCID 5003444Sodium cyanoborohydrideHCID 12047933(R)-N-(5-(2-amino-1-hydroxyethyl)-2-hydroxyphenyl)methanesulfonamideHCID 18173737Ethyl 4-{4-[4-(dimethoxymethyl)anilino]-1-piperidinyl}benzoate

生成物 1

HCID 699870244-[4-(4-[2-[(2R)-2-Hydroxy-2-(4-hydroxy-3-methanesulfonylamino-phenyl)-ethylamino]-ethyl)-phenylamino)-piperidin-1-yl]-benzoic acid ethyl ester

試薬・触媒・溶媒 4

HCID 887Methanol溶媒HCID 6342Acetonitrile溶媒HCID 6344Dichloromethane溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

Ethyl 4-{4-[4-(dimethoxymethyl)anilino]-1-piperidinyl}benzoate (0.63 g, 01.53 mmol) was added to a pre-prepared mixture of sodium iodide (0.572 g, 3.82 mmol) and trichloro(methyl)silane (0.36 mL, 3.07 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, tetrahydrofuran, acetic acid (0.091 mL, 1.53 mmol), N-{5-[(1R)-2-amino-1-hydroxyethyl]-2-hydroxyphenyl}methanesulfonamide (0.377 g, 0.1.53 mmol) followed by sodium cyanoborohydride (0.105 g, 1.53 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). The hydrochoride salt of the title compound was generated from anhydrous etheral hydrochloric acid in ethyl acetate (0.14 g, 0.221 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-1becad67b8f3465f831458974e05296f
出典データセット
uspto-grants-2002_09
特許番号
US06451814B1

関連ノート

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