Triethylamine → 3-(3-{(5,6-Dimethoxypyridin-3-yl)-[4-(5-methyl-[1,2,4]oxadiazol-3-yl)phenylamino]methyl}-5-oxo-4,5-dihydro-[1,2,4]triazol-1-yl)thiophene-2-carboxylic acid

Temperature

90 °C

After adding 38 mg of 3-hydrazinothiophene-2-carboxylic acid methyl ester and 0.030 ml of triethylamine to a solution of 100 mg of {2-(5,6-dimethoxypyridin-3-yl)-2-[4-(5-methyl-[1,2,4]oxadiazol-3-yl)phenylimino]-1-methylsulfanylethylidene}carbamic acid methyl ester in 1 ml of DMF, the mixture was stirred at 90° C. for 12 hours under a nitrogen atmosphere. The reaction mixture was concentrated, and the residue was dissolved in 1.5 ml of methanol and 0.1 ml of acetic acid. After adding 100 mg of sodium cyanotrihydroborate to the solution, the mixture was stirred at room temperature for 3 hours. Next, 1.0 ml of a 5N aqueous sodium hydroxide solution was added and the mixture was stirred at room temperature for 2 hours. After then adding 0.3 ml of acetic acid, the reaction mixture was crudely purified by reverse-phase high performance liquid chromatography (acetonitrile-water, 0.1% acetic acid) to give a crude product of 3-(3-{(5,6-dimethoxypyridin-3-yl)-[4-(5-methyl-[1,2,4]oxadiazol-3-yl)phenylamino]methyl}-5-oxo-4,5-dihydro-[1,2,4]triazol-1-yl)thiophene-2-carboxylic acid.

1. concentrationThe reaction mixture was concentrated
2. dissolutionthe residue was dissolved in 1.5 ml of methanol
3. additionAfter adding 100 mg of sodium cyanotrihydroborate to the solution
4. stirringthe mixture was stirred at room temperature for 3 hours
5. additionNext, 1.0 ml of a 5N aqueous sodium hydroxide solution was added
6. stirringthe mixture was stirred at room temperature for 2 hours
7. additionAfter then adding 0.3 ml of acetic acid
8. customthe reaction mixture was crudely purified by reverse-phase high performance liquid chromatography (acetonitrile-water, 0.1% acetic acid)

ORD record

ord-11fd338e905b48e384dd931e2db4a63d

Source dataset

uspto-grants-2010_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07816522B2