Stable SNS-595 compositions and methods of preparation

1. A process for preparing a substantially pure SNS-595 substance, comprising:

(a) reacting Compound 3

 with a first aqueous base followed by neutralizing to obtain a primary SNS-595 hydrate;

(b) dehydrating the primary SNS-595 hydrate from step (a) and reacting the dehydrated product with a second aqueous base followed by neutralizing to obtain a secondary SNS-595 hydrate; and

(c) dehydrating the secondary SNS-595 hydrate obtained in step (b) to obtain the substantially pure SNS-595 substance.

2. The process of claim 1 , wherein the first and second aqueous bases are selected from potassium hydroxide, sodium hydroxide, and lithium hydroxide; the neutralizations of steps (a) and (b) are accomplished with acetic acid; and the dehydration of steps (b) and (c) are accomplished with ethanol.

3. The process of claim 2 , wherein the substantially pure SNS-595 substance obtained from step (c) comprises about 0 to 0.01% Compound 4

based on total weight of the substantially pure SNS-595 substance.

4. The process of claim 1 , wherein Compound 3 is obtained by reaction of Compound 1

with Compound 2

5. A process for preparing substantially pure Compound 3

comprising reacting Compound 1

with Compound 2

in the presence of N,N-diisopropylethylamine and water to obtain substantially pure Compound 3.

6. The process of claim 5 , wherein the substantially pure Compound 3 obtained comprises from 0 to about 0.1% Compound 1

based on total weight of substantially pure Compound 3.

7. A process for preparing a substantially pure SNS-595 substance, comprising:

(a) reacting Compound 1

with Compound 2

in the presence of N,N-diisopropylethylamine and water to obtain substantially pure Compound 3

(b) reacting the substantially pure Compound 3 with an aqueous base followed by neutralizing to obtain a primary SNS-595 hydrate; and

(c) dehydrating the primary SNS-595 hydrate obtained in step (a) to obtain the substantially pure SNS-595 substance.

8. The process of claim 7 , wherein the substantially pure Compound 3 obtained comprises about 0 to 0.1% Compound 1

based on total weight of the substantially pure Compound 3.

9. The process of claim 7 , wherein the substantially pure SNS-595 substance obtained from step (c) comprises about 0 to 0.01% Compound 4

based on total weight of the substantially pure SNS-595 substance.

10. The process of claim 7 , wherein the substantially pure SNS-595 substance obtained from step (b) comprises about 0 to 0.02% Compound 5

based on total weight of the substantially pure SNS-595 substance.

11. The process of claim 2 , wherein the first and second aqueous bases are sodium hydroxide.

12. The process claim 1 , wherein the SNS-595 substance obtained from step (c) comprises 0 to 0.02% Compound 5:

based on total weight of the SNS-595 substance.

13. The process of claim 1 , wherein the SNS-595 substance obtained from step (c) comprises 0 to 0.1% Compound 7:

based on total weight of the SNS-595 substance.

14. The process of claim 1 , wherein Compound 3 is obtained by reaction of Compound 1

with Compound 2

15. The process of claim 1 , comprising:

(a) reacting Compound 1

 with Compound 2

 in the presence of DIPEA and water to obtain Compound 3

(b) reacting Compound 3 with a first aqueous base followed by neutralizing to obtain a primary SNS-595 hydrate;

(c) dehydrating the primary SNS-595 hydrate obtained in step (b) to form a SNS-595 substance;

(d) reacting the SNS-595 substance from step (c) with a second aqueous base followed by neutralizing to obtain a secondary SNS-595 hydrate; and

(e) dehydrating the secondary SNS-595 hydrate obtained in step (d) to obtain SNS-595 substance.

16. The process claim 1 , wherein the SNS-595 substance obtained from step (c) comprises

about 0 to 0.02% Compound 4

about 0 to 0.02% Compound 5:

and

about 0 to 0.1% Compound 7:

based on total weight of the SNS-595 substance.