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

HRID 516440Notes

Reaction equation

HRID 516440 reaction equation
[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

Participants

9

Reactant 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

Product 1

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

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-7ebbacd29781469a942d8344b2262580
Source dataset
uspto-grants-2015_08
Patent number
US09108934B2

Reaction notes

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