Crystalline salt forms of Boc-D-Arg-DMT-Lys-(Boc)-Phe-NH
Disclosed are various crystalline salt forms of Boc-D-Arg-DMT-Lys(Boc)-Phe-NH 2 .
1. A crystalline form of the freebase of Compound (I),
(Boc)-D-Arg-DMT-Lys(Boc)-Phe-NH 2 ).
2. The crystalline form of claim 1 , wherein said crystalline form is characterized by an endothermic event in its thermogravimetry differential thermal analysis at an onset of about 168.5° C.
3. The crystalline form of claim 1 , wherein said crystalline form is characterized by an endothermic event in its thermogravimetry differential thermal analysis at a peak at about 175.9° C.
4. A method of preparing a crystalline form of the freebase of Compound (I), the method comprising:
a) preparing a mixture comprising the freebase of Compound (I) and a solvent; and
b) crystallizing the freebase of Compound (I) from the mixture.
5. The method of claim 4 , wherein the solvent is selected from methanol, ethanol, or trifluoroethanol.
6. The method of claim 5 , wherein the solvent is methanol.
7. The method of claim 4 , wherein the mixture is a solution, and the step of crystallizing the freebase of Compound (I) from the mixture comprises adding an anti-solvent, thereby causing the freebase of Compound (I) to precipitate.
8. The method of claim 7 , wherein the ratio of the solvent to the anti-solvent in the solution is about 3:1 to about 1:3 v/v.
9. The method of claim 7 , wherein the ratio of the solvent to the anti-solvent in the solution is about 3:1 v/v.
10. The method of claim 7 , wherein the ratio of the solvent to the anti-solvent in the solution is about 1:3 v/v.
11. The method of claim 7 , wherein the antisolvent is added at about 5 to about 50° C.
12. The method of claim 7 , wherein the antisolvent is added at about 50° C.
13. The method of claim 7 , wherein the antisolvent is added at about 5° C.
14. The method of claim 7 , wherein the anti-solvent is selected from acetonitrile, ethyl acetate, tetrahydrofuran, acetone, methyl ethyl ketone, toluene, tert-butyl methyl ether, and heptane.
15. A method of making Compound (II), the method comprising
(a) preparing a mixture of a crystalline form of the freebase of compound (I), a scavenger, and a solvent
(b) adding an acid to the mixture, thereby making compound (II)
16. The method of claim 15 , wherein
the scavenger is triisopropylsilane, the solvent is 2,2,2-trifluoroethanol and
the acid is hydrochloric acid.
17. The method of claim 16 , wherein the mixture is a slurry.
18. The method of claim 17 , further comprising isolating compound (II) from the mixture.