Tetrahydrofuran → Isobutyric Acid (R)-2-[N'-(5-Acetyl-2H-pyrazole-3-carbonyl)-N-(5'-chloro-2'-fluorobiphenyl-4-ylmethyl)hydrazino]-1-carboxyethyl Ester

HRID 541546Notes

Reaction equation

[C:1](Cl)(=[O:5])[CH:2]([CH3:4])[CH3:3].[C:7]([C:10]1[CH:11]=[C:12]([C:15]([NH:17][N:18]([CH2:34][C@@H:35]([OH:39])[C:36]([OH:38])=[O:37])[CH2:19][C:20]2[CH:25]=[CH:24][C:23]([C:26]3[CH:31]=[C:30]([Cl:32])[CH:29]=[CH:28][C:27]=3[F:33])=[CH:22][CH:21]=2)=[O:16])[NH:13][N:14]=1)(=[O:9])[CH3:8].C1COCC1>>[C:7]([C:10]1[CH:11]=[C:12]([C:15]([NH:17][N:18]([CH2:34][C@@H:35]([O:39][C:1](=[O:5])[CH:2]([CH3:4])[CH3:3])[C:36]([OH:38])=[O:37])[CH2:19][C:20]2[CH:25]=[CH:24][C:23]([C:26]3[CH:31]=[C:30]([Cl:32])[CH:29]=[CH:28][C:27]=3[F:33])=[CH:22][CH:21]=2)=[O:16])[NH:13][N:14]=1)(=[O:9])[CH3:8]

Participants

Reactant 3

HCID 8028Tetrahydrofuran

HCID 62325Isobutyryl chloride

HCID 86705116(R)-3-[N'-(5-Acetyl-2H-pyrazole-3-carbonyl)-N-(5'-chloro-2'-fluorobiphenyl-4-ylmethyl)hydrazino]-2-hydroxypropionic acid

Product 1

HCID 86705119Isobutyric Acid (R)-2-[N'-(5-Acetyl-2H-pyrazole-3-carbonyl)-N-(5'-chloro-2'-fluorobiphenyl-4-ylmethyl)hydrazino]-1-carboxyethyl EsterYield 40.7%

Procedure

Isobutyryl chloride (23.4 μL, 221.1 μmol) and (R)-3-[N′-(5-acetyl-2H-pyrazole-3-carbonyl)-N-(5′-chloro-2′-fluorobiphenyl-4-ylmethyl)hydrazino]-2-hydroxypropionic acid (10.5 mg, 22.1 μmol) were combined in THF (108 μL, 1.3 mmol), and stirred overnight at room temperature. The solvent was evaporated and the residue was purified by preparative HPLC to yield the title compound (4.9 mg) as a TFA salt. MS m/z [M+H]+ calc'd for C26H26ClFN4O6, 545.15. found 545.1.

Workup

customThe solvent was evaporated
customthe residue was purified by preparative HPLC

Sources & evidence

ORD record: ord-efe6d75af6dd4534b63a5b9589c3bf48
Source dataset: uspto-grants-2014_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08871792B2

Reaction notes

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