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

반응식

HRID 1281625 반응식
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]

참가 물질

13

반응물 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

생성물 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

시약·촉매·용매 4

HCID 887Methanol용매HCID 6342Acetonitrile용매HCID 6344Dichloromethane용매HCID 8028Tetrahydrofuran용매

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-1becad67b8f3465f831458974e05296f
출처 데이터셋
uspto-grants-2002_09
특허 번호
US06451814B1

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