US 10,889,548 B2
Compositions and methods for inhibiting dihydroorotate dehydrogenase
Vikram S. Kumar, Boston, MA (US); David P. Hesson, Malvern, PA (US); Ping Huang, Shanghai (CN); Mo Jia, Shanghai (CN); and Xianjun You, Shanghai (CN)
Assigned to Clear Creek Bio, Inc., Cambridge, MA (US)
Filed by Clear Creek Bio, Inc., Cambridge, MA (US)
Filed on Mar. 26, 2019, as Appl. No. 16/364,446.
Claims priority of provisional application 62/682,440, filed on Jun. 8, 2018.
Claims priority of provisional application 62/655,407, filed on Apr. 10, 2018.
Claims priority of provisional application 62/648,320, filed on Mar. 26, 2018.
Prior Publication US 2019/0292154 A1, Sep. 26, 2019
Int. Cl. C07D 215/52 (2006.01)
CPC C07D 215/52 (2013.01) 6 Claims
 
1. A method of making a 2-(2′-halo-1-1′-biphenyl-4-yl)-quinoline carboxylic acid, the method comprising:
incubating a compound of formula (I) with a compound of formula (II) in a mixture comprising a base at a temperature of from 60° C. to 70° C. for from 15 hours to 30 hours; and
adding an acid, to the mixture, thereby creating a compound of formula (III) according to following reaction:

OG Complex Work Unit Drawing
wherein:
R1, R2, R3, and R4 are independently H, F, Cl, Br, I, CH3, CF3, SCH3 or CH2 CH3, at least two of R1, R2, R3, and R4 being H;
R5 is H, alkoxy of 1-3 carbon atoms, or alkyl of 1-2 carbon atoms;
R6 and R7 are independently H, F, Cl, Br, alkyl of 1-5 carbon atoms, NO2, OH, CF3 or OCH3;
X is a halogen.