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

反応式

HRID 516440 の反応式
[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

参加物

9

反応物 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

生成物 1

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

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-7ebbacd29781469a942d8344b2262580
出典データセット
uspto-grants-2015_08
特許番号
US09108934B2

関連ノート

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