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Process for the purification of (4-((methylamino)methyl)phenyl)boronic acid and 8-fluoro-2-(4-((methylamino)methyl)phenyl)-4,5-dihydro-1H-azepino[5,4,3-cd]indol-6(3H)-one

IP.com Disclosure Number: IPCOM000250486D
Publication Date: 2017-Jul-25
Document File: 1 page(s) / 205K

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Process for the purification of (4-((methylamino)methyl)phenyl)boronic acid and 8-

fluoro-2-(4-((methylamino)methyl)phenyl)-4,5-dihydro-1H-azepino[5,4,3-cd]indol-

6(3H)-one

(4-((Methylamino)methyl)phenyl)boronic acid (referred herein as compound 2) is an

intermediate in the preparation of 8-fluoro-2-(4-((methylamino)methyl)phenyl)-4,5-dihydro-

1H-azepino[5,4,3-cd]indol-6(3H)-one (referred to herein as compound 1).

Compound 2 was prepared starting from (4-formylphenyl)boronic acid which first had been

reacted with methylamine to form 4-((methylimino)methyl)phenylboronic acid. In the next

step, 4-((methylimino)methyl)phenylboronic acid was hydrogenated over metal catalyst such

as Raney Nickel, Pd/C or Pt/C, in ethanol or methanol solution, to give compound 2.

Compound 2, prepared on such way, contained up to 0.5% of (4-

(aminomethyl)phenyl)boronic acid (referred herein as compound 3) which, while used in

preparation of compound 1, lead to formation of 2-(4-(aminomethyl)phenyl)-8-fluoro-4,5-

dihydro-1H-azepino[5,4,3-cd]indol-6(3H)-one (referred herein as compound 4), an impurity

of compound 1.

To achieve optimal purification of compound 1 from compound 4, the following two

procedures, based on formation of Schiff base with different ketones or aldehydes, were

applied.

For example, compound 2, contaminated with compound 3, was treated with some ketone

(such as acetone or methyl ethyl ketone) in a mixture with alcohol (such as methanol or

ethanol) at elevated temperature in order...