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PROCESS FOR PREPARING A 4-METHYLAMINO-3-NITROBENZOYL COMPOUND

IP.com Disclosure Number: IPCOM000246837D
Publication Date: 2016-Jul-06
Document File: 3 page(s) / 210K

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The IP.com Prior Art Database

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PROCESS FOR PREPARING A 4-METHYLAMINO-3-NITROBENZOYL COMPOUND

[0001]          The present document discloses a process for preparing ethyl 3-{[4-(methylamino)-3-nitrobenzoyl]pyridin-2-ylamino}propanoate, which is represented by Formula (I):

 (I).

[0002]          The present document discloses a process for preparing ethyl 3-{[4-(methylamino)-3-nitrobenzoyl]pyridin-2-ylamino}propanoate (compound I), said process comprising:

a)       reacting 4-methylamino-3-nitrobenzoic acid with a suitable activating agent in an organic solvent, to give an activated carboxylic acid intermediate;

b)       reacting the activated carboxylic acid intermediate obtained in step (a) with ethyl 3-(pyridin-2-ylamino)propanoate; and

c)       isolating the obtained ethyl 3-{[4-(methylamino)-3-nitrobenzoyl]pyridin-2-ylamino}propanoate (compound I).

[0003]          The activating agent can be selected from the list comprising thionyl chloride, oxalyl chloride, phosphorus trichloride, phosphorus oxychloride, phosphorus pentachloride, cyanuric chloride, 1,1’-carbonyldiimidazole, N-ethyl-N’-(3-dimethylaminopropyl)carbodiimide, N,N’-dicyclohexylcarbodiimide, N,N’-diisopropyl carbodiimide, and ethyl chloroformate, preferably thionyl chloride.

[0004]          The organic solvent can be selected from the list comprising anisole, tert-butylmethyl ether, chlorobenzene, cumene, cyclohexane, 1,2-dimethoxyethane, N,N-dimethylacetamide, N,N-dimethylformamide, 1,4-dioxane, ethyl ether, heptane, hexane, methylcyclohexane, 2-methyltetrahydrofuran, pentane, tetrahydrofuran, tetralin, toluene, xylene, and mixtures thereof.

[0005]          The ethyl 3-{[4-(methylamino)-3-nitrobenzoyl]pyridin-2-ylamino}propanoate (compound I) obtained from the above process is characterized by a X-Ray Powder Diffraction (XRPD) plot comprising at least diffraction peaks (2-theta, 2θ) at 19.6, 20.7 and 21.9 degrees (± 0.2 degrees), more preferably at 12.3, 13.7, 18.5, 19.6, 20.7 and 21.9 degrees (± 0.2 degrees), and even more preferably at 9.2, 10.0, 11.3, 12.3, 13.7, 14.9, 18.1, 18.5, 19.6, 20.2, 20.7, 21.6, 21.9, 22.7, 23.8, 24.1, 24.9, 25.2, 25.8, 27.0, 27.6, 28.0 and 30.0 degrees (± 0.2 degrees).

[0006]          The obtained ethyl 3-{[4-(methylamino)-3-nitrobenzoyl]pyridin-2-ylamino}propanoate (compound I) is a useful intermediate for the synthesis of Dabigatren etexilate.

X-Ray Powder D...