Production method for 2-fluoro-4-borono-l-phenylalanine, and precursor of 2-fluoro-4-borono-l-phenylalanine

Patent metadata

Field	Value
Publication number	US-2017283441-A1
Application number	US-201715625909-A
Country	US
Kind code	A1
Filing date	Jun 16, 2017
Priority date	Dec 17, 2013
Publication date	Oct 5, 2017
Grant date	—

Abstract

The present invention involves preparing compounds represented by the following formula:

from a compound of the following formula:

In these formulae: R 1 represents a Br group, an iodine group, a Cl group, an NO 2 group, or an NH 2 group; R 2 represents a halogen group, an NO 2 group, an NH 2 group, Sn(R 6 ) 3 , N═N—NR 7 R 8 , OSO 2 R 9 , N R 10 R 11 , phenyliodonium, a heterocyclic group iodine, boric acid, or a borate ester; R 30 represents a protective group PG 1 ; R 40 or R 50 represent hydrogen, a protective group PG 2 , or C 6 H 5 (C 6 H 5 )C═N, in which NR 40 R 50 are together.

First claim

What is claimed is:

1 . A method for producing a compound represented by the following formula:

(where X represents F or 18 F; R 30 represents hydrogen or a protecting group PG 1 for a carboxyl group; R 40 or R 50 independently represents hydrogen or a protecting group PG 2 for an amino group, or NR 40 R 50 are combined together to form C 6 H 5 (C 6 H 5 )C═N; and R 15 and R 16 are combined together with a boron atom to form a ring serving as a protecting group for boron atom, comprising:
reacting a compound represented by the following formula:

where R 1 represents a bromo group, an iodo group, a chloro group, a nitro group, or an amino group; R 2 represents a halogen group, a nitro group, an amino group, Sn(R 6 ) 3 , N═N—NR 7 R 8 , OSO 2 R 9 , NR 10 R 11 , substituted or unsubstituted phenyl iodo, a substituted or unsubstituted heterocyclic iodo group, or boric acid or a boric ester (where R 6 represents an alkyl group having 1 to 7 carbon atoms or a benzyl group; R 7 and R 8 are the same or different, each representing hydrogen, an alkyl group having 1 to 7 carbon atoms, a halogen-substituted alkyl group having 1 to 7 carbon atoms, or an optionally substituted phenyl group, or else R 7 and R 8 are combined together with N to form a 3- to 7-membered cyclic structure; R 9 represents an alkyl group having 1 to 7 carbon atoms, a halogen-substituted alkyl group having 1 to 7 carbon atoms, or an optionally substituted phenyl group; R 10 and R 11 are the same or different, each representing an alkyl group having 1 to 7 carbon atoms, a halogen-substituted alkyl group having 1 to 7 carbon atoms, or an optionally substituted phenyl group, or else R 10 and R 11 are combined together with N to form a 3- to 7-membered cyclic structure); and R 30 , R 40 , and R 50 have the same meaning as described above,
wherein said reacting comprises radiating said compound in the presence of a catalyst and a ligand.

2 . The method of claim 1 , wherein the catalyst is a palladium catalyst.

3 . The method of claim 2 , wherein the palladium catalyst is selected from the group consisting of a palladium chloride cinnamyl complex, palladium acetate, and trisdibenzylideneacetonedipalladium.

4 . The method of claim 1 , wherein the radiating comprises microwave radiation.

5 . The method of claim 4 , wherein the microwave radiation is conducted from room temperature to 200° C.

6 . The method of claim 4 , wherein the reaction period is from 1 minute to 60 minutes.

7 . The method of claim 1 , wherein the ligand is a phosphorus-based ligand.

8 . The method of claim 7 , wherein the phosphorus-based ligand is selected from the group consisting of tricyclohexylphosphine, 2-dicyclohexylphosphino-2,4,6-triisopropylbiphenyl, 2-dicyclohexylphosphino-2,-(N,N)-dimethylaminobiphenyl, 3,5-dimethoxy-2-dicyclohexylphosphino-2,4,6-triisopropylbiphenyl, and 3,5-dimethoxy-2-ditert-butylphosphino-2,4,6-triisopropylbiphenyl.

9 . The method of claim 1 , wherein the reacting is conducted in the presence of a base.

10 . The method of claim 9 , wherein the base is selected from the group consisting of lithium hydroxide, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, and trimethylamine.

11 . The method of claim 1 , wherein the reacting is conducted in a solvent selected from the group consisting of toluene, dioxane, and DMDO.

Assignees

• Stella Pharma Corp
• Univ Osaka Prefect Public Corp

Inventors

• Takenaka Hiroshi
• Ohta Yoichiro
• Taguchi Yusuke
• Ueda Sayuri
• Ishino Yuko
• Yoshikawa Tomohiro
• Nakashima Hideki
• Uehara Kohki
• Kirihata Mitsunori

Classifications

• Y02P20/55

  Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups · CPC title

• C07C251/24

  having carbon atoms of imino groups bound to carbon atoms of six-membered aromatic rings · CPC title

• C07F5/027 Primary

  Organoboranes and organoborohydrides · CPC title

• C07C271/22

  to carbon atoms of hydrocarbon radicals substituted by carboxyl groups · CPC title

• C07C229/36 Primary

  with at least one amino group and one carboxyl group bound to the same carbon atom of the carbon skeleton · CPC title