# US 11,999,724 B2 · Method for producing diarylpyridine derivatives > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,999,724 B2 - Document ID: US11999724B2 - Status: Granted - Kind: B2 - Application number: 17/252,469 - Filed: 2019-07-03 - Published: 2021-06-24 - Granted: 2024-06-04 - Earliest claimed: 2018-07-04 - Assignees: Daiichi Sankyo Company, Limited - Applicants: Daiichi Sankyo Company, Limited - Inventors: Yuichi Aki; Fumihiko Toriyama; Natsuki Sakurai; Ai Kameda; Tomokazu Ogura - Web page: https://patentgrep.com/patent/US11999724B2 ## CPC - C07D 405/14: containing three or more hetero rings - B01J 23/44: Palladium - C07B 61/00: Other general methods - C07D 319/12: not condensed with other rings - C07D 405/12: linked by a chain containing hetero atoms as chain links - A61K 31/444: containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone - A61P 35/00: Antineoplastic agents - C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08) - B01J: CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS - C07B: GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR (preparation of carboxylic acid esters by telomerisation C07C67/47; telomerisation C08F) - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract The present invention relates to a novel method for producing diarylpyridine derivatives, and the object of the present invention is to provide a novel, industrially useful method. The present inventors developed a novel method for synthesizing pyridine rings without using palladium, a strong base, or a high-temperature reaction. In particular, they successfully developed a method that can be used to synthesize iminium salts as intermediates, synthesize cyano compounds from these iminium salts, and cyclize the cyano compounds into pyridines under very mild reaction conditions. ## Claims ### Claim 1 A production method comprising the step of reacting a compound represented by Formula (I): with a chlorinating agent and dimethylformamide to obtain a compound represented by Formula (II): or a salt thereof. ### Claim 2 (depends on 1) The method according to claim 1, wherein the chlorinating agent is oxalyl chloride. ### Claim 3 (depends on 1) The method according to claim 1, further comprising reacting the compound represented by Formula (II) or a salt thereof with a compound represented by Formula (III): in the presence of a base to obtain a compound represented by Formula (IV): or a salt thereof. ### Claim 4 (depends on 3) The method according to claim 3, wherein the base is 2,6-lutidine. ### Claim 5 (depends on 3) The method according to claim 3, further comprising reacting the compound represented by Formula (IV) or a salt thereof with benzylamine to obtain a compound represented by Formula (V): or a salt thereof. ### Claim 6 A production method comprising the steps of: (i) reacting a compound represented by Formula (I′) with a Wittig reagent; (ii) reacting the compound obtained in step (i) with a chlorinating agent and dimethylformamide; (iii) reacting the compound obtained in step (ii) with a compound represented by Formula (III): in the presence of a base; and (iv) reacting the compound obtained in step (iii) with benzylamine to obtain a compound represented by Formula (V): or a salt thereof. ### Claim 7 (depends on 6) The method according to claim 6, wherein the Wittig reagent in step (i) is Ph3P(Cl)CH2OMe. ### Claim 8 (depends on 6) The method according to claim 6, wherein the chlorinating agent in step (ii) is oxalyl chloride. ### Claim 9 (depends on 6) The method according to claim 6, wherein the base in step (iii) is 2,6-lutidine. ### Claim 10 (depends on 5) The method according to claim 5, further comprising reacting the compound represented by Formula (V) or salt thereof with hydrogen in a solvent and in the presence of a palladium on carbon catalyst to obtain a compound represented by Formula (VI): or a salt thereof. ### Claim 11 (depends on 10) The method according to claim 10, wherein the compound represented by Formula (V) or salt thereof is a hydrochloric acid salt of a compound represented by Formula (V), and the solvent is 1-propanol or N-methylpyrrolidone. ### Claim 12 (depends on 10) The method according to claim 10, further comprising condensing the compound represented by Formula (VI) or salt thereof with a compound represented by Formula (VII): or a salt thereof to obtain a compound represented by Formula (VIII): or a salt thereof. ### Claim 13 (depends on 12) The method according to claim 12, wherein the compound represented by Formula (VIII) or a salt thereof is a sulfuric acid salt of the compound represented by Formula (VIII). ### Claim 14 A production method, comprising reacting a compound represented by Formula (VI): or a salt thereof with a compound represented by Formula (VII): or a salt thereof to obtain a compound represented by Formula (VIII): or a salt thereof. ### Claim 15 (depends on 14) The method according to claim 14, wherein the compound represented by Formula (VIII) or a salt thereof is a sulfuric acid salt of the compound represented by Formula (VIII). ### Claim 16 (depends on 14) The method according to claim 14, further comprising reacting a compound represented by Formula (V) or a salt thereof: with hydrogen in a solvent to obtain the compound represented by Formula (VI) or a salt thereof. ### Claim 17 (depends on 16) The method according to claim 16, wherein the compound represented by Formula (V) or salt thereof is a hydrochloric acid salt of a compound represented by Formula (V), and the solvent is 1-propanol or N-methylpyrrolidone. ### Claim 18 (depends on 16) The method according to claim 16, wherein reacting a compound represented by Formula (V) or a salt thereof with hydrogen is performed in the presence of a palladium on carbon catalyst.