Dimethylacetamide → (R)-3-[N-(5'-Chloro-2'-fluorobiphenyl-4-ylmethyl)-N'-(2-hydroxythiazole-5-carbonyl)hydrazino]-2-hydroxypropionic Acid Ethyl Ester

Participants

Role	Name	HCID	Charge
Reactant	Dimethylacetamide	HCID 31374	—
Reactant	Diisopropylethylamine	HCID 81531	—
Reactant	Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)	HCID 9886157	—
Reactant	2-Oxo-2,3-dihydro-1,3-thiazole-5-carboxylic acid	HCID 20061617	—
Reactant	(R)-3-[N-(5'-Chloro-2'-fluorobiphenyl-4-ylmethyl)hydrazino]-2-hydroxypropionic Acid Ethyl Ester	HCID 67972425	—
Product	(R)-3-[N-(5'-Chloro-2'-fluorobiphenyl-4-ylmethyl)-N'-(2-hydroxythiazole-5-carbonyl)hydrazino]-2-hydroxypropionic Acid Ethyl Ester	HCID 178472581	38.9%

Reaction Steps

2-Hydroxy-5-thiazolecarboxylic acid (9.0 mg, 62 μmol) and HATU (28.3 mg, 74 μmol) were stirred in DMA (0.5 mL, 5 mmol) for 10 minutes. (R)-3-[N-(5′-Chloro-2′-fluorobiphenyl-4-ylmethyl)hydrazino]-2-hydroxypropionic acid ethyl ester (22.7 mg, 62 μmol) and DIPEA (32.4 μL, 186 μmol) were added, and resulting mixture was stirred at room temperature for 2 hours. The mixture was then concentrated under reduced pressure and the residue was dissolved in 50% AcOH-water (1.5 mL), filtered, purified by reverse phase preparative HPLC, and lyophilized to yield the title compound (11.9 mg, purity 96%) as a TFA salt. MS m/z [M+H]+ calc'd for C22H21ClFN3O5S, 494.09. found 494.4.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08871792B2
Source dataset	uspto-grants-2014_10
ORD ID	ord-217a706821344daf99baf1e7735a2ffc
Source note	uspto-grants-2014_10