# US 10,370,357 B2 · Method for producing sulfonyl chloride compound

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- Number: US 10,370,357 B2
- Document ID: US10370357B2
- Status: Granted
- Kind: B2
- Application number: 15/899,055
- Filed: 2018-02-19
- Published: 2018-06-21
- Granted: 2019-08-06
- Earliest claimed: 2013-02-28
- Assignees: Takeda Pharmaceutical Company Limited
- Applicants: Takeda Pharmaceutical Company Limited
- Inventors: Keisuke Majima
- Web page: https://patentgrep.com/patent/US10370357B2

## CPC

- C07D 401/12: linked by a chain containing hetero atoms as chain links
- A61K 9/2866: {Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose}
- C07D 213/71: to which a second hetero atom is attached
- A61K 9/2018: {Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates}
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- 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)

## Abstract

An object of the present invention is to provide a production method of an intermediate used in the production method of a sulfonylpyrrole compound useful as a pharmaceutical product. The present invention relates to a method of producing sulfonylpyrrole compound (VI) by reacting a pyridine-3-sulfonic acid compound with phosphorus pentachloride in a solvent of chlorobenzene or trifluoromethylbenzene to give a pyridine-3-sulfonyl chloride compound, reacting the compound without isolation with compound (III) to give compound (IV), and subjecting the compound (IV) to a reductive amination reaction. wherein R2 is a hydrocarbon group etc. and R3 and R4 are each a hydrogen atom etc., wherein R2 is an optionally substituted pyridin-3-yl group, and the other symbols are as defined above, wherein R5 is an alkyl group and the other symbols are as defined above.

## Claims

### Claim 1

A production method of a compound represented by the formula (VI):
wherein
R1 is a pyridin-3-yl group optionally substituted by 1 to 3 substituents selected from (i) halogen, (ii) cyano, (iii) C1-6 alkyl optionally substituted by 1-5 halogens, (iv) C1-6 alkoxy optionally substituted by 1-5 halogens, (v) an amino group optionally substituted by C1-6 alkyl and (vi) C1-6 alkoxy-carbonyl,
R2 is
(a) a C6-14 aryl group optionally substituted by 1-5 substituents selected from (i) a halogen atom, (ii) cyano, (iii) C1-6 alkyl optionally substituted by 1-5 halogens, (iv) C1-6 alkoxy optionally substituted by 1-5 halogens, (v) acetyl, (vi) C3-7 cycloalkyl, (vii) C1-6 alkylsulfonyl, (viii) C1-6 alkylthio optionally substituted by 1-5 halogens and (ix) C1-6 alkylsulfinyl,
(b) a thienyl group optionally substituted by 1 to 3 substituents selected from (i) a halogen atom, (ii) cyano, (iii) C1-6 alkyl optionally substituted by 1-5 halogens, (iv) C1-6 alkoxy optionally substituted by 1-5 halogens and (v) acetyl, or
(c) a pyridyl group optionally substituted by 1 to 4 substituents selected from (i) a halogen atom, (ii) cyano, (iii) C1-6 alkyl optionally substituted by 1-5 halogens, (iv) C1-6 alkoxy optionally substituted 1-5 halogens, (v) acetyl and (vi) nitro,
R3 and R4 are each independently a hydrogen atom, a C1-6 alkyl group, a C1-6 alkyl-carbonyl group, a fluorine atom or a chlorine atom,
and R5 is an alkyl group or a salt thereof,
comprising reacting, without isolation, the pyridine-3-sulfonyl chloride compound represented by the following formula (II):
R1—SO2Cl (II)
wherein R1 is as defined above, which is obtained by reacting a pyridine-3-sulfonic acid compound with phosphorus pentachloride in a solvent of chlorobenzene or trifluoromethylbenzene,
with a compound represented by the formula (III):
wherein each symbol is as defined above, or a salt thereof to produce a compound represented by the formula (IV):
wherein each symbol is as defined above,
or a salt thereof, and reacting the compound with a compound represented by the formula (V):
R5—NH2 (V)
wherein R5 is as defined above, or a salt thereof in the presence of a reducing agent.

### Claim 2 (depends on 1)

The production method according to claim 1, wherein R1 is an unsubstituted pyridin-3-yl group,
R2 is a 2-fluorophenyl group,
R3 and R4 are each a hydrogen atom, and
R5 is a methyl group.