Ethanol → (R)-3-{N-(5'-Chloro-2'-fluorobiphenyl-4-ylmethyl)-N'-[1-(3-chlorophenyl)-5-oxo-4,5-dihydro-1H-[1,2,4]triazole-3-carbonyl]hydrazino}-2-hydroxypropionic Acid

HRID 541504Notes

Reaction equation

HRID 541504 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([N:8]2[C:12](=[O:13])[NH:11][C:10]([C:14]([OH:16])=O)=[N:9]2)[CH:5]=[CH:6][CH:7]=1.CN(C(ON1N=NC2C=CC(=CC1=2)Cl)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN(C=O)C.C([O:49][C:50](=[O:71])[C@H:51]([OH:70])[CH2:52][N:53]([CH2:55][C:56]1[CH:61]=[CH:60][C:59]([C:62]2[CH:67]=[C:66]([Cl:68])[CH:65]=[CH:64][C:63]=2[F:69])=[CH:58][CH:57]=1)[NH2:54])C.CCN(C(C)C)C(C)C.CCO.[Li+].[OH-].O>>[Cl:68][C:66]1[CH:65]=[CH:64][C:63]([F:69])=[C:62]([C:59]2[CH:60]=[CH:61][C:56]([CH2:55][N:53]([CH2:52][C@@H:51]([OH:70])[C:50]([OH:71])=[O:49])[NH:54][C:14]([C:10]3[NH:11][C:12](=[O:13])[N:8]([C:4]4[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[CH:3]=4)[N:9]=3)=[O:16])=[CH:57][CH:58]=2)[CH:67]=1

Participants

9

Reactant 8

HCID 702EthanolHCID 962WaterHCID 3939Lithium HydroxideHCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 42624899O-(6-Chlorobenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphateHCID 67972425(R)-3-[N-(5'-Chloro-2'-fluorobiphenyl-4-ylmethyl)hydrazino]-2-hydroxypropionic Acid Ethyl EsterHCID 1360859201-(3-Chlorophenyl)-5-oxo-4,5-dihydro-1H-[1,2,4]triazole-3-carboxylic Acid

Product 1

HCID 136480968(R)-3-{N-(5'-Chloro-2'-fluorobiphenyl-4-ylmethyl)-N'-[1-(3-chlorophenyl)-5-oxo-4,5-dihydro-1H-[1,2,4]triazole-3-carbonyl]hydrazino}-2-hydroxypropionic AcidYield 46.6%

Procedure

1-(3-Chlorophenyl)-5-oxo-4,5-dihydro-1H-[1,2,4]triazole-3-carboxylic acid (75.8 mg, 316 μmol) and HCTU (131 mg, 316 μmol) were combined in DMF (1.3 mL, 17.2 mmol). and stirred at room temperature for 15 minutes. (R)-3-[N-(5′-Chloro-2′-fluorobiphenyl-4-ylmethyl)hydrazino]-2-hydroxypropionic acid ethyl ester (105 mg, 287 μmol) and DIPEA (150 mL, 862 μmol) were added, and the resulting mixture was stirred at room temperature for 15 minutes. The mixture was evaporated under reduced pressure. The residue was dissolved in EtOH (1.0 mL, 17.2 mmol) and a solution of 1 M LiOH in water (1.4 mL, 1.4 mmol) was added. The resulting mixture was stirred at room temperature for 1 hour, then evaporated under reduced pressure. The residue was purified by reverse phase preparative HPLC to yield the title compound (75 mg, purity 100%) as a TFA salt. MS m/z [M+H]+ calc'd for C25H20Cl2FN5O5, 560.08. found 559.6.

Workup

  1. stirringthe resulting mixture was stirred at room temperature for 15 minutes
  2. customThe mixture was evaporated under reduced pressure
  3. stirringThe resulting mixture was stirred at room temperature for 1 hour
  4. customevaporated under reduced pressure
  5. customThe residue was purified by reverse phase preparative HPLC

Sources & evidence

ORD record
ord-48bffbdbd190455e81411c457964a470
Source dataset
uspto-grants-2014_10
Patent number
US08871792B2

Reaction notes

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