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 5-methyl-2-oxo-[1,3]dioxol-4-ylmethyl Ester

HRID 541528Notes

Reaction equation

HRID 541528 reaction equation
C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.[O:15]=[C:16]1[N:20]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[N:19]=[C:18]([C:27]([OH:29])=O)[NH:17]1.[CH3:30][C:31]1[O:35][C:34](=[O:36])[O:33][C:32]=1[CH2:37][O:38][C:39](=[O:60])[C@H:40]([OH:59])[CH2:41][N:42]([CH2:44][C:45]1[CH:50]=[CH:49][C:48]([C:51]2[CH:56]=[C:55]([Cl:57])[CH:54]=[CH:53][C:52]=2[F:58])=[CH:47][CH:46]=1)[NH2:43].CCN(C(C)C)C(C)C>CN(C=O)C>[CH3:30][C:31]1[O:35][C:34](=[O:36])[O:33][C:32]=1[CH2:37][O:38][C:39](=[O:60])[C@H:40]([OH:59])[CH2:41][N:42]([CH2:44][C:45]1[CH:46]=[CH:47][C:48]([C:51]2[CH:56]=[C:55]([Cl:57])[CH:54]=[CH:53][C:52]=2[F:58])=[CH:49][CH:50]=1)[NH:43][C:27]([C:18]1[NH:17][C:16](=[O:15])[N:20]([C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)[N:19]=1)=[O:29]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 86705088(R)-3-[N-(5'-chloro-2'-fluorobiphenyl-4-ylmethyl)hydrazino]-2-hydroxypropionic acid 5-methyl-2-oxo-[1,3]dioxol-4-ylmethyl esterHCID 1354826545-Oxo-1-phenyl-4,5-dihydro-1H-[1,2,4]triazole-3-carboxylic Acid

Product 1

HCID 136344433(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 5-methyl-2-oxo-[1,3]dioxol-4-ylmethyl EsterYield 31.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

EDC (127 mg, 660 μmol) and HOBt (89 mg, 660 μmol) were added to a solution of 5-oxo-1-phenyl-4,5-dihydro-1H-[1,2,4]triazole-3-carboxylic acid (150 mg, 330 μmol) and (R)-3-[N-(5′-chloro-2′-fluorobiphenyl-4-ylmethyl)hydrazino]-2-hydroxypropionic acid 5-methyl-2-oxo-[1,3]dioxol-4-ylmethyl ester (68 mg, 330 μmol) in DMF (10 mL). DIPEA (86 mg, 660 μmol) was added, and the resulting mixture was stirred for 5 hours at room temperature. The mixture was then washed with saturated aqueous NaCl (2×30 mL) and extracted with EtOAc (2×50 mL). The combined organic layers were dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was purified by column chromatography (PE:EtOAc=1:1) to yield the title compound as a white solid (67 mg). LC-MS: 638.2 [M+H]+. 1H-NMR (400 MHz, DMSO-d6): δ 2.13 (s, 3H), 3.31-3.16 (m, 2H), 4.18-4.21 (q, 2H), 4.35 (br, 1H), 4.98-5.01 (m, 2H), 5.54 (br, 1H), 7.26-7.90 (m, 12H), 9.98 (s, 1H), 12.74 (s, 1H).

Workup

  1. washThe mixture was then washed with saturated aqueous NaCl (2×30 mL)
  2. extractionextracted with EtOAc (2×50 mL)
  3. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by column chromatography (PE:EtOAc=1:1)

Sources & evidence

ORD record
ord-efa244b5007346df9860dcc72d32922b
Source dataset
uspto-grants-2014_10
Patent number
US08871792B2

Reaction notes

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