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PROCESS FOR PREPARING A BENZOFURANCARBOXAMIDE COMPOUND

IP.com Disclosure Number: IPCOM000246376D
Publication Date: 2016-Jun-02
Document File: 4 page(s) / 34K

Publishing Venue

The IP.com Prior Art Database

Abstract

The present document discloses a process for preparing 4-amino-5-chloro-2,3-dihydro-N-[1-(3-methoxypropyl)-4-piperidinyl]-7-benzofurancarboxamide butanedioate (1:1)

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PROCESS FOR PREPARING A BENZOFURANCARBOXAMIDE COMPOUND


[0001] The present document discloses a process for preparing 4-amino-5- chloro-2,3-dihydro-N-[1-(3-methoxypropyl)-4-piperidinyl]-7-benzofurancarboxamide butanedioate (1:1), which is represented by Formula (I):

(I).


[0002] The present document discloses a process for preparing 4-amino-5- chloro-2,3-dihydro-N-[1-(3-methoxypropyl)-4-piperidinyl]-7-benzofurancarboxamide butanedioate (1:1) (compound I), said process comprising:

a) obtaining a solution comprising 4-amino-5-chloro-2,3-dihydro-N-[1-(3- methoxypropyl)-4-piperidinyl]-7-benzofurancarboxamide in a protic solvent;


b) optionally, decolorizing the solution obtained in step (a); and

c) combining the solution obtained in steps (a) or (b) with a solution of succinic acid in a protic solvent.


[0003] The protic solvent can be selected from the list comprising methanol, ethanol, 1-propanol, isopropanol, water and mixtures thereof, preferably isopropanol or a mixture of isopropanol and water.


[0004] The 4-amino-5-chloro-2,3-dihydro-N-[1-(3-methoxypropyl)-4-piperidinyl]-7- benzofurancarboxamide butanedioate (1:1) obtained from the above process is characterized by a X-Ray Powder Diffraction (XRPD) plot comprising at least diffraction peaks (2-theta, 2θ) at 15.5 and 22.1 degrees (± 0.2 degrees), more preferably at 7.7, 13.7, 15.5, 20.2, 20.8, 22.1, 23.3 and 24.1 degrees (± 0.2 degrees), and even more preferably at 7.7, 9.1, 9.9, 10.1, 13.7, 15.5, 15.7, 18.3, 19.6, 19.9,
20.2, 20.8, 22.1, 23.3, 24.1, 24.6, 25.1, 26.3, 27.3, 28.3, 28.7 and 29.8 degrees (± 0.2 degrees).


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[0005] The present document further discloses a process for preparing 4-amino- 5-chloro-2,3-dihydro-N-[1-(3-methoxypropyl)-4-piperidinyl]-7-benzofurancarboxamide monohydrate, said process comprising:

a) reacting 4-amino-5-chloro-2,3-dihydro-7-benzofurancarboxylic acid with 1,1'-carbonyldiimidazole in an organic solvent;

b) combining the reaction mixture obtained in step (a) with 1-(3- methoxypropyl)-4-piperidinamine or a salt thereof;


c) combining the reaction mixture obtained in step (b) with water; and


d) removing (totally or partially) the organic solvent.


[0006] The organic solvent can be selected from the list comprising acetonitrile, chloroform, cyclopentyl methyl ether, dichloromethane, 1,4-dioxane, isopropyl ether, 2-methyltetrahydrofuran, tert-butyl methyl ether, tetrahydrofuran, and mixtures thereof, preferably tetrahydrofuran.


[0007] The 4-amino-5-chloro-2,3-dihydro-N-[1-(3-methoxypropyl)-4-piperidinyl]-7- benzofurancarboxamide monohydrate obtained from the above process is characterized by a X-Ray Powder Diffraction (XRPD) plot comprising at least diffraction peaks (2-theta, 2θ) at 7.9, 17.9 and 23.1 degrees (± 0.2 degrees), more preferably at 7.9, 14.4, 15.6, 17.9, 19.0, 23.1, 24.2, 26.1 and 27.6 degrees (± 0.2 degrees), and even more preferably at 7.9, 14.4, 15.6, 17.9, 19.0, 20.3, 21.8, 23.1,
23.9, 24.2, 24.8, 25.1, 26.1, 27.6 and 2...