US 12,331,047 B2
Synthesis for 3-bromo-5-(2-ethylimidazo[1, 2-alpha]pyridine-3-carbonyl)-2-hydroxybenzonitrile
Dongfang Shi, Fremont, CA (US); Changjin Fu, Suzhou (CN); Jie Gu, Suzhou (CN); Min Zhang, Suzhou (CN); Weiwei Gong, Suzhou (CN); and Pengfei Li, Suzhou (CN)
Assigned to Atom Therapeutics Co., Ltd, Hangzhou (CN)
Appl. No. 17/310,123
Filed by Atom Therapeutics Co., Ltd, Hangzhou (CN)
PCT Filed Jan. 17, 2020, PCT No. PCT/CN2020/072582
§ 371(c)(1), (2) Date Jul. 18, 2021,
PCT Pub. No. WO2020/147803, PCT Pub. Date Jul. 23, 2020.
Claims priority of application No. 201910057056.3 (CN), filed on Jan. 19, 2019; and application No. 202010037085.6 (CN), filed on Jan. 14, 2020.
Prior Publication US 2022/0041593 A1, Feb. 10, 2022
Int. Cl. C07D 471/04 (2006.01)
CPC C07D 471/04 (2013.01) 6 Claims
 
1. A method for synthesizing a compound represented by formula (III), comprising step A or step B,

OG Complex Work Unit Chemistry
Step A: a compound represented by formula (I) and a compound represented by formula (II) are first heated in an organic solvent to react, and the resulting reaction product and a base are heated in the presence of water to continue the reaction to obtain a compound represented by formula (III);
Step B: a compound represented by formula (I), a compound represented by formula (II), and the base are heated in an organic solvent to react, and the resulting reaction product is heated in the presence of water to continue the reaction to obtain a compound represented by formula (III);

OG Complex Work Unit Chemistry
wherein, R1 is H or C1-3 alkyl, R2 is H, —CN, I or Br, R3 is H, I or Br, and R4 is Cl, Br or I; the organic solvent is selected from the group consisting of toluene, xylene, ethyl acetate, isopropyl acetate, isopropanol, ethanol, N-methyl-2-pyrrolidone (NMP), tert-butanol, dimethylformamide (DMF) and acetonitrile;
wherein the base is selected from the group consisting of sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, triethylamine, diisopropylethylamine, lithium hydroxide, sodium hydroxide and potassium hydroxide.