Citric Acid → 1-(3,4-Difluoro-benzyl)-2-oxo-1,2-dihydro-pyridine-3-carboxylic acid (4-bromo-thiophen-2-ylmethyl)-amide

Participants

Role	Name	HCID	Charge
Reactant	Citric Acid	HCID 311	—
Reactant	Bicarbonate Ion	HCID 769	—
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	(4-Bromothiophen-2-yl)methanamine	HCID 42282037	—
Reactant	1-(3,4-Difluorobenzyl)-2-oxo-1,2-dihydropyridine-3-carboxylic acid	HCID 53427969	—
Solvent	Dichloromethane	HCID 6344	—
Solvent	Sodium chloride; water	HCID 57417360	—
Product	1-(3,4-Difluoro-benzyl)-2-oxo-1,2-dihydro-pyridine-3-carboxylic acid (4-bromo-thiophen-2-ylmethyl)-amide	HCID 59362711	—

Reaction Steps

C-(4-Bromo-thiophen-2-yl)-methylamine (0.200 g, 0.00104 mol;), 1-(3,4-Difluoro-benzyl)-2-oxo-1,2-dihydro-pyridine-3-carboxylic acid (0.251 g, 0.000946 mol;), N,N,N′,N′-Tetramethyl-O-(7-azabenzotriazol-1-yl)uronium Hexafluorophosphate (0.40 g, 0.0010 mol;), N,N-Diisopropylethylamine (800 uL, 0.005 mol;), and Methylene chloride (9.1 mL, 0.14 mol;) were added to a 50 mL round bottom and stirred for 2 to 3 hours. LC-MS showed the formation of product at 1.78 438.92. Workup consisted of dilution with methylene chloride washing 1×with citric acid, 1× with saturated bicarbonate, and 1× with brine before drying and concentration to give the crude material. The crude was then purified by combiflash 0-100 percent hexanes/Ethyl acetate to give pure material. ES (+) MS m/e=438.92

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08778977B2
Source dataset	uspto-grants-2014_07
ORD ID	ord-1951dc89e932443a965c495934d6af89
Source note	uspto-grants-2014_07