Sodium Iodide → Butyric acid (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-hydroxypropionyloxymethyl Ester

HRID 541533Notes

Reaction equation

HRID 541533 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.[C:38]([O:43][CH2:44]Cl)(=[O:42])[CH2:39][CH2:40][CH3:41].[Na+].[I-].CC1C=CC=C(C)N=1>CN(C=O)C.O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([F:37])=[C:6]([C:8]2[CH:9]=[CH:10][C:11]([CH2:14][N:15]([CH2:31][C@@H:32]([OH:36])[C:33]([O:35][CH2:44][O:43][C:38](=[O:42])[CH2:39][CH2:40][CH3:41])=[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:12][CH:13]=2)[CH:7]=1

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 79372,6-LutidineHCID 2725008Chloromethyl butanoateHCID 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 136344438Butyric acid (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-hydroxypropionyloxymethyl EsterYield 10%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution 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, 335 μmol) in dry DMF (6 mL) was added chloromethyl butyrate (68 mg, 503 mmol), NaI (101 mg, 670 mmol), and 2,6-dimethylpyridine (143 mg, 1.3 mmol) in portions at room temperature. The resulting mixture was stirred at room temperature for 8 hours. Water (12 mL) was added and the mixture was extracted with EtOAc (3×20 mL). The combined organic layers were dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was purified by column chromatography (PE:EtOAc=3:1) to yield the title compound as a white solid (21 mg). LC-MS: 625.9 [M+H]+. 1H NMR (DMSO-d6, 400 MHz) δ 0.84 (t, J=7.4 Hz, 3H), 1.45-1.56 (m, 2H), 2.29 (t, J=7.3 Hz, 2H), 3.31-3.17 (m, 2H), 4.18-4.35 (m, 2H), 4.35 (t, J=5.3 Hz, 1H), 5.68-5.79 (m, 2H), 7.28 (t, J=7.4 Hz, 1H), 7.34-7.40 (m, 1H), 7.43-7.55 (m, 7H), 7.58 (dd, J=6.8, 2.6 Hz, 1H), 7.90 (d, J=7.6 Hz, 2H), 9.98 (s, 1H), 12.76 (s, 1H).

Workup

  1. extractionthe mixture was extracted with EtOAc (3×20 mL)
  2. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  3. concentrationconcentrated in vacuo
  4. customThe residue was purified by column chromatography (PE:EtOAc=3:1)

Sources & evidence

ORD record
ord-ad5eb426f17349b3a18dfa8527f74097
Source dataset
uspto-grants-2014_10
Patent number
US08871792B2

Reaction notes

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