Ethanol → (2R,4R)-5-(3'-Chlorobiphenyl-4-yl)-2-hydroxy-4-[(5-oxo-1-phenyl-4,5-dihydro-1H-[1,2,4]triazole-3-carbonyl)amino]pentanoic Acid

HRID 516475Notes

Reaction equation

HRID 516475 reaction equation
[O:1]=[C:2]1[N:6]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[N:5]=[C:4]([C:13]([OH:15])=O)[NH:3]1.CN(C(ON1N=NC2C=CC(=CC1=2)Cl)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.C([O:52][C:53](=[O:73])[C@H:54]([OH:72])[CH2:55][C@H:56]([NH2:71])[CH2:57][C:58]1[CH:63]=[CH:62][C:61]([C:64]2[CH:69]=[CH:68][CH:67]=[C:66]([Cl:70])[CH:65]=2)=[CH:60][CH:59]=1)C.CCO.[Li+].[OH-].O>CN(C=O)C>[Cl:70][C:66]1[CH:65]=[C:64]([C:61]2[CH:60]=[CH:59][C:58]([CH2:57][C@@H:56]([NH:71][C:13]([C:4]3[NH:3][C:2](=[O:1])[N:6]([C:7]4[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=4)[N:5]=3)=[O:15])[CH2:55][C@@H:54]([OH:72])[C:53]([OH:73])=[O:52])=[CH:63][CH:62]=2)[CH:69]=[CH:68][CH:67]=1

Participants

9

Reactant 7

HCID 702EthanolHCID 962WaterHCID 3939Lithium HydroxideHCID 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 1354826545-Oxo-1-phenyl-4,5-dihydro-1H-[1,2,4]triazole-3-carboxylic Acid

Product 1

HCID 136344442(2R,4R)-5-(3'-Chlorobiphenyl-4-yl)-2-hydroxy-4-[(5-oxo-1-phenyl-4,5-dihydro-1H-[1,2,4]triazole-3-carbonyl)amino]pentanoic AcidYield 3.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

5-Oxo-1-phenyl-4,5-dihydro-1H-[1,2,4]triazole-3-carboxylic acid (42.3 mg, 206 μmol) and HCTU (128 mg, 310 μmol) were combined in DMF, and stirred for 10 minutes at room temperature. DIPEA (72 μL, 413 μmol) and (2R,4R)-4-amino-5-(3′-chlorobiphenyl-4-yl)-2-hydroxypentanoic acid ethyl ester (50 mg, 0.1 mmol) were added, and the resulting mixture was stirred at room temperature overnight. The mixture was combined with EtOH (402 μL, 6.9 mmol) and 1 M LiOH in water (1.1 mL, 1.1 mmol). The mixture was stirred at room temperature for 1 hour, evaporated under reduced pressure, and purified by preparative HPLC to yield the title compound (1.8 mg) as a TFA salt. MS m/z [M+H]+ calc'd for C26H23ClN4O5, 507.14. found 507.2.

Workup

  1. stirringthe resulting mixture was stirred at room temperature overnight
  2. stirringThe mixture was stirred at room temperature for 1 hour
  3. customevaporated under reduced pressure
  4. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-50c523112b4c44c6b26cd503e22025e2
Source dataset
uspto-grants-2015_08
Patent number
US09108934B2

Reaction notes

Loading…