Synthesis of triethylenetetramines
Methods and intermediates for synthesizing triethylenetetramine and salts thereof, as well as novel triethylenetetramine salts and their crystal structure, and triethylenetetramine salts of high purity.
1. A polymorph of triethylenetetramine disuccinate, wherein said polymorph has a DSC extrapolated onset and peak melting temperatures of from between about 170° C. to about 190° C.
2. The polymorph of claim 1 wherein said DSC extrapolated onset and peak melting temperature are 180.05 and 179.91° C., respectively.
3. The polymorph of claim 1 , wherein said polymorph has infrared peaks at wavenumbers at 3148, 1645, 1549, 1529, 1370, 1271, 1172, 1152, and 1033.
4. A Form I polymorph of triethylenetetramine dihydrochloride, wherein said Form I polymorph is characterized by a DSC extrapolated onset and peak melting temperatures of between about 111° C. to 132° C.
5. The Form I polymorph of claim 4 wherein said DSC extrapolated onset and peak melting temperatures are 121.96 and 122.78° C., respectively.
6. The Form I polymorph of claim 4 , wherein said Form I polymorph is characterized by infrared peaks at wavenumbers 1043, 1116, 1300, 1328, 1557, 2833, 2895, 2902, and 3216.
7. A Form II polymorph of triethylenetetramine dihydrochloride, wherein said Form II polymorph is characterized by a DSC extrapolated onset and peak melting temperature of from between about 106° C. to about 126° C.
8. The Form II polymorph of claim 7 wherein said DSC extrapolated onset and peak melting temperatures are 116.16 and 116.76° C., respectively.
9. The Form II polymorph of claim 7 , wherein said Form II polymorph is characterized by infrared peaks at wave numbers 1039, 1116, 1352, 1519, 2954, 2986, 3276, and 3298.
10. A pharmaceutical composition comprising substantially pure triethylenetetramine disuccinate of claim 1 .
11. A pharmaceutical composition comprising substantially pure triethylenetetramine disuccinate of claim 1 and a pharmaceutically acceptable excipient.
12. A substantially pure triethylenetetramine disuccinate according to claim 1 .
13. The polymorph of a triethylenetetramine disuccinate according to claim 1 wherein the polymorph is a crystal having the structure defined by the co-ordinates of Table 3B.
14. The polymorph of a triethylenetetramine disuccinate according to claim 1 wherein the polymorph is a crystal having the structure defined by the co-ordinates of Table 3C.
15. A crystalline form of triethylenetetramine disuccinate.
16. A polymorph according to claim 1 which exhibits an infrared spectrum substantially as depicted in FIG. 7 .
17. A polymorph according to claim 1 which exhibits a DSC graph substantially as that depicted in FIG. 8 .
18. The Form I polymorph according to claim 4 which exhibits an infrared spectrum substantially as depicted in FIG. 9 .
19. The Form I polymorph according to claim 4 which exhibits a DSC graph substantially as that depicted in FIG. 10 .
20. The Form II polymorph according to claim 7 which exhibits an infrared spectrum substantially as depicted in FIG. 11 .
21. The Form II polymorph according to claim 7 which exhibits a DSC graph substantially that depicted in as FIG. 12 .
22. The crystalline form of triethylenetetramine disuccinate according to claim 15 having the structure defined by the co-ordinates of Table 3B.
23. The crystalline form of triethylenetetramine disuccinate according to claim 15 having the structure defined by the co-ordinates of Table 3C.
24. The crystalline form of triethylenetetramine disuccinate according to claim 15 having a C 2/c (no. 15) space group with measured unit cell dimensions of a=14.059(5) Å, b=9, 169(5) Å, c=13.647(5) Å, and β=92.47(0) Å.
25. The crystalline form of triethylenetetramine disuccinate according to claim 15 having the x-ray powder diffraction spectrum substantially as depicted in FIG. 16 .