DNT-maleate and methods of preparation thereof
(S)-N,N-Dimethyl-3-(1-naphthalenyloxy)-3-(2-thienyl)propanamine maleate (DNT-maleate) and polymorphs of DNT-maleate, compositions of DNT-maleate and its polymorphs, processes for the preparation of DNT-maleate and its polymorphs, and processes for the preparation of duloxetine hydrochloride from DNT-maleate are provided.
1. A compound (S)-N,N-dimethyl-3-(1-naphthalenyloxy)-3-(2-thienyl)propanamine maleate) having the following formula:
2. A composition comprising the compound of claim 1 , wherein the compound is present in said composition with at least about 99.96% enantiomeric purity by HPLC.
3. A composition comprising the compound of claim 1 , wherein the compound is present in said composition with at least about 95% enantiomeric purity by HPLC.
4. A composition comprising the compound of claim 1 , wherein the compound is present in said composition with at least about 85% enantiomeric purity by HPLC.
5. A composition comprising the compound of claim 1 , wherein the compound is present in said composition with at least about 50% enantiomeric purity by HPLC.
6. A composition comprising the compound of claim 1 , wherein the R-enantiomer of DNT-maleate is undetectable by HPLC; wherein the detection limit for the HPLC method is 0.02%.
7. A crystalline form of (S)-N,N-dimethyl-3-(1-naphthalenyloxy)-3-(2-thienyl)-propanamine maleate):
characterized by a powder XRD pattern with peaks at about 9.4°, 14.0°, 18.7°, 23.3°, and 24.9° 2θ±0.2° 2θ.
8. The crystalline form of claim 7 , further characterized by X-ray powder diffraction peaks at about 20.6°, 24.6°, and 24.9° 2θ±0.2° 2θ.
9. The crystalline form of claim 7 , wherein the crystalline form is present in a batch at a polymorphic purity level of at least about 50% by weight.
10. A crystalline form of (S)-N,N-dimethyl-3-(1-naphthalenyloxy)-3-(2-thienyl)-propanaznine maleate):
characterized by a powder XRD pattern with peaks at about 14.4°, 18.5°, 23.1°, 27.2°, and 31.3° 2θ±0.2° 2θ.
11. The crystalline form of claim 10 , further characterized by X-ray powder diffraction peaks at about 13.9°, 20.3°, and 26.3° 2θ±0.2° 2θ.
12. The crystalline form of claim 10 , wherein the crystalline form is present in a batch at a polymorphic purity level of at least about 50% by weight.
13. A crystalline form of (S)-N,N-dimethyl-3-(1-naphthalenyloxy)-3-(2-thienyl)-propanamine maleate):
characterized by a powder XRD pattern with peaks at about 9.4°, 18.7°, 23.4°, and 25.3° 2θ±0.2° 2θ.
14. The crystalline form of claim 13 , further characterized by X-ray powder diffraction peaks at about 14.0°, 20.6°, 24.9°, 28.1°, and 29.5° 2θ±0.2° 2θ.
15. The crystalline form of claim 13 , wherein the crystalline form is present in a batch at a polymorphic purity level of at least about 50% by weight.