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Crystalline form of (S)-(+)-N,N-dimethyl-3-(1-naphthalenyloxy)-3-(2-thienyl)propanamine oxalate and the preparation thereof

IP.com Disclosure Number: IPCOM000126392D
Publication Date: 2005-Jul-14
Document File: 2 page(s) / 80K

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The IP.com Prior Art Database

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This is the abbreviated version, containing approximately 67% of the total text.

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CRYSTALLINE FORM OF (S)-(+)-N,N-DIMETHYL-3-(1-NAPHTHALENYLOXY)- 3-(2-THIENYL)PROPANAMINE OXALATE AND THE PREPARATION THEREOF

    (S)-(+)-N-methyl-3-(1-naphthalenyloxy)-3-(2-thienyl)propanamine is a dual reuptake inhibitor of the neurotransmitters serotonin and norepinephrine. It has been found to be useful in the treatment of stress urinary incontinence (SUI), depression, and pain management. The primary raw material in its synthesis is (S)-(+)-N,N-Dimethyl-3-(1- naphthalenyloxy)-3-(2-thienyl)propanamine oxalate (ATNAP-Oxal).

    The preparation of ATNAP-Oxal is described in European Patent Application No. EP 457,559 and International Patent Application Publication WO 2004/056795.

    A crystalline form of ATNAP-Oxal was found, and characterized by an X-ray powder diffraction pattern with peaks at about 15.6, 17.2, 17.8, 22.7 and 23.4 ± 0.2 degrees two-theta. This crystalline form is further characterized by X-ray powder diffraction peaks at 6.6, 19.0,
20.4 and 27.4 ± 0.2 degrees two-theta, substantially as depicted in Figure 1 herein below.

    This crystalline form was obtained by combining (S)-2-(1-N,N-dimethyl-3- hydroxy)propyl amino)-thiophene with DMSO, Potassium hydroxide and 18-Crown-6. The reaction mixture is then combined with 4-fluoro naphthalene. After extraction work-up, ethyl acetate and oxalic acid are added to yield the ATNAP-Oxal crystalline form. This process was performed according to the following example (Example 4 of WO 2004/056795).

Example
(S)-2-(1-N,N-di...