1,2-Dichloroethane → (R)-3-[N-(5'-Chloro-2'-fluorobiphenyl-4-ylmethyl)-N'-(5-oxo-1-phenyl-4,5-dihydro-1H-[1,2,4]triazole-3-carbonyl)hydrazino]-2-hydroxypropionic Acid 2,2,3,3,3-Pentafluoropropyl Ester

HRID 541531Notes

Reaction equation

HRID 541531 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([F:37])=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([CH2:14][N:15]([CH2:31][C@@H:32]([OH:36])[C:33]([OH:35])=[O:34])[NH:16][C:17]([C:19]3[NH:23][C:22](=[O:24])[N:21]([C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)[N:20]=3)=[O:18])=[CH:10][CH:9]=2)[CH:7]=1.[F:38][C:39]([F:46])([C:42]([F:45])([F:44])[F:43])[CH2:40]O.C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.CCN(C(C)C)C(C)C>CN(C=O)C.O>[F:38][C:39]([F:46])([C:42]([F:45])([F:44])[F:43])[CH2:40][O:34][C:33](=[O:35])[C@H:32]([OH:36])[CH2:31][N:15]([CH2:14][C:11]1[CH:10]=[CH:9][C:8]([C:6]2[CH:7]=[C:2]([Cl:1])[CH:3]=[CH:4][C:5]=2[F:37])=[CH:13][CH:12]=1)[NH:16][C:17]([C:19]1[NH:23][C:22](=[O:24])[N:21]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[N:20]=1)=[O:18]

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 98722,2,3,3,3-PentafluoropropanolHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 136344432(R)-3-[N-(5'-chloro-2'-fluorobiphenyl-4-ylmethyl)-N'-(5-oxo-1-phenyl-4,5-dihydro-1H-[1,2,4]triazole-3-carbonyl)hydrazino]-2-hydroxypropionic acid

Product 1

HCID 136344436(R)-3-[N-(5'-Chloro-2'-fluorobiphenyl-4-ylmethyl)-N'-(5-oxo-1-phenyl-4,5-dihydro-1H-[1,2,4]triazole-3-carbonyl)hydrazino]-2-hydroxypropionic Acid 2,2,3,3,3-Pentafluoropropyl EsterYield 8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of (R)-3-[N-(5′-chloro-2′-fluorobiphenyl-4-ylmethyl)-N′-(5-oxo-1-phenyl-4,5-dihydro-1H-[1,2,4]triazole-3-carbonyl)hydrazino]-2-hydroxypropionic acid (200 mg, 380 μmol), 2,2,3,3,3-pentafluoropropan-1-ol (114 mg, 760 μmol), HOBT (103 mg, 760 μmol), EDC (145 mg, 760 μmol) and DIPEA (200 mg, 1.5 mmol) in DMF (5.0 mL) was stirred at room temperature overnight. The mixture was then poured into water (30 mL) and extracted with EtOAc (3×20 mL). The combined organic layers were washed with saturated aqueous NaCl (30 mL), dried over anhydrous Na2SO4, and concentrated in vacuo. The residue was purified by column chromatography (PE:EtOAc=2:1) to yield the title compound as a white solid (20 mg). LC-MS: 658 [M+H]+. 1H NMR (400 MHz, CDCl3) δ 3.44-3.40 (m, 2H), 4.25 (br, 2H), 4.58-4.61 (m, 3H), 7.14-7.08 (m, 1H), 7.41-7.55 (m, 8H), 7.84-7.92 (m, 3H).

Workup

  1. extractionextracted with EtOAc (3×20 mL)
  2. washThe combined organic layers were washed with saturated aqueous NaCl (30 mL)
  3. dry with materialdried over anhydrous Na2SO4
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by column chromatography (PE:EtOAc=2:1)

Sources & evidence

ORD record
ord-72ff7a7a259a4d9986932093c87847cd
Source dataset
uspto-grants-2014_10
Patent number
US08871792B2

Reaction notes

Loading…