Ethanol → (2R,4R)-5-(3'-Chlorobiphenyl-4-yl)-2-hydroxy-4-{[5-(4-methoxybenzyloxy)-1-methyl-1H-pyrazole-3-carbonyl]amino}pentanoic Acid

HRID 516440

반응식

HRID 516440 반응식
[CH3:1][O:2][C:3]1[CH:19]=[CH:18][C:6]([CH2:7][O:8][C:9]2[N:13]([CH3:14])[N:12]=[C:11]([C:15]([OH:17])=O)[CH:10]=2)=[CH:5][CH:4]=1.CN(C(ON1N=NC2C=CC(=CC1=2)Cl)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN(C=O)C.CCN(C(C)C)C(C)C.C([O:61][C:62](=[O:82])[C@H:63]([OH:81])[CH2:64][C@H:65]([NH2:80])[CH2:66][C:67]1[CH:72]=[CH:71][C:70]([C:73]2[CH:78]=[CH:77][CH:76]=[C:75]([Cl:79])[CH:74]=2)=[CH:69][CH:68]=1)C.CCO.[Li+].[OH-].O>>[Cl:79][C:75]1[CH:74]=[C:73]([C:70]2[CH:69]=[CH:68][C:67]([CH2:66][C@@H:65]([NH:80][C:15]([C:11]3[CH:10]=[C:9]([O:8][CH2:7][C:6]4[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:19][CH:18]=4)[N:13]([CH3:14])[N:12]=3)=[O:17])[CH2:64][C@@H:63]([OH:81])[C:62]([OH:82])=[O:61])=[CH:72][CH:71]=2)[CH:78]=[CH:77][CH:76]=1

참가 물질

9

반응물 8

HCID 702EthanolHCID 962WaterHCID 3939Lithium HydroxideHCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 42624899O-(6-Chlorobenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphateHCID 86682253(2R,4R)-4-amino-5-(3'-chlorobiphenyl-4-yl)-2-hydroxypentanoic acid ethyl esterHCID 867051385-(4-Methoxybenzyloxy)-1-methyl-1H-pyrazole-3-carboxylic Acid

생성물 1

HCID 86705139(2R,4R)-5-(3'-Chlorobiphenyl-4-yl)-2-hydroxy-4-{[5-(4-methoxybenzyloxy)-1-methyl-1H-pyrazole-3-carbonyl]amino}pentanoic Acid수율 70.5%

실험 절차

5-(4-Methoxy-benzyloxy)-1-methyl-1H-pyrazole-3-carboxylic acid (118.8 mg, 453 mol) was combined with HCTU (187.3 mg, 453 μmol) and DMF (2.0 mL, 25.9 mmol). The mixture was stirred at room temperature for 15 minutes. DIPEA (225 μL, 1.3 mmol) and (2R,4R)-4-amino-5-(3′-chlorobiphenyl-4-yl)-2-hydroxypentanoic acid ethyl ester (150 mg, 430 μmol) were added and the mixture was stirred at room temperature for 15 minutes. The solvent was removed in vacuo. EtOH (1.5 mL, 25.9 mmol) was added, followed by a solution of 1 M LiOH in water (4.3 mL, 4.3 mmol). The mixture was stirred at room temperature for 1 hour. The solvent was removed in vacuo and the product was purified by reverse phase chromatography to yield the title compound (171 mg).

후처리

  1. stirringthe mixture was stirred at room temperature for 15 minutes
  2. customThe solvent was removed in vacuo
  3. stirringThe mixture was stirred at room temperature for 1 hour
  4. customThe solvent was removed in vacuo
  5. customthe product was purified by reverse phase chromatography

출처 및 근거

ORD 기록
ord-7ebbacd29781469a942d8344b2262580
출처 데이터셋
uspto-grants-2015_08
특허 번호
US09108934B2

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