Dimethylformamide → (2R,3R)-3-(1-((2'-(N-Acetylsulfamoyl)biphenyl-4-yl)methyl)-5-propyl-1H-pyrazole-3-carboxamido)-2-hydroxy-4-phenylbutanoic Acid

Participants

Role	Name	HCID	Charge
Reactant	Dimethylformamide	HCID 6228	—
Reactant	Diisopropylethylamine	HCID 81531	—
Reactant	(2R,3R)-3-amino-2-hydroxy-4-phenylbutanoic acid	HCID 638739	—
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	1-(2'-acetylsulfamoylbiphenyl-4-ylmethyl)-5-propyl-1H-pyrazole-3-carboxylic acid	HCID 66757639	—
Product	(2R,3R)-3-(1-((2'-(N-Acetylsulfamoyl)biphenyl-4-yl)methyl)-5-propyl-1H-pyrazole-3-carboxamido)-2-hydroxy-4-phenylbutanoic Acid	HCID 66757852	97%

Reaction Conditions

Temperature	45 °C

Reaction Steps

A solution of 1-(2′-acetylsulfamoylbiphenyl-4-ylmethyl)-5-propyl-1H-pyrazole-3-carboxylic acid (250 mg, 570 μmol), HATU (215 mg, 566 μmol) and DIPEA (592 μL, 3.4 mmol) in DMF (18 mL, 230 mmol) was stirred to pre-activate the acid. After 15 minutes, (2R,3R)-3-amino-2-hydroxy-4-phenylbutyric acid (110 mg, 566 μmol) was added The resulting solution was stirred at 45° C. overnight. The mixture was concentrated, re-dissolved in water/MeCN/TFA and purified using reverse phase liquid chromatography to yield the title compound (197 mg, 97% purity). MS m/z: [M+H]+ calcd for C32H34N4O7S, 619.22; found 619.6.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08119634B2
Source dataset	uspto-grants-2012_02
ORD ID	ord-ad759d8cf3a044158bcc99170535b766
Source note	uspto-grants-2012_02