Synthesis of cerdulatinib
The present disclosure provides processes for the preparation of cerdulatinib, which is of formula I: or a salt thereof. The disclosure also provides intermediates and processes for the preparation of the intermediates useful in the preparation of cerdulatinib or a salt thereof.
1. A process for preparing Compound A, wherein Compound A is Compound A-2, a salt of Compound A-2, Compound A-3, a salt of Compound A-3, or a mixture thereof:
wherein the process comprises contacting Compound C:
or a salt thereof with an oxidizing agent;
wherein Compound C is prepared by contacting Compound D-1:
or a salt thereof with formamide and sodium ethoxide.
2. The process of claim 1 , wherein the oxidizing agent is meta-chloroperoxybenzoic acid.
3. The process of claim 1 , wherein a molar ratio of the oxidizing agent to Compound C is about 2:1 to about 4:1.
4. The process of claim 1 , wherein a molar ratio of the oxidizing agent to Compound C is about 2.5:1 to about 3.5:1.
5. The process of claim 1 , wherein a molar ratio of the oxidizing agent to Compound C is about 1.1:1 to about 2:1.
6. The process of claim 1 , wherein the contacting of Compound C or the salt thereof with the oxidizing agent is at a temperature of about −10° C. to about 20° C.
7. The process of claim 1 , wherein the contacting of Compound C or the salt thereof with the oxidizing agent is in a first solvent.
8. The process of claim 7 , wherein the first solvent is N-methylpyrrolidone (NMP).
9. The process of claim 1 , wherein Compound D-1 is prepared by a method comprising contacting Compound K
or a salt thereof with cyclopropylamine or a salt thereof to form Compound D-1.
10. The process of claim 1 , wherein formamide and Compound D-1 are in a molar ratio of about 5:1 to about 15:1.
11. The process of claim 1 , wherein the contacting of Compound D-1 with formamide and sodium ethoxide is in a second solvent.
12. The process of claim 11 , wherein the second solvent is THF.
13. The process of claim 1 , wherein the contacting of Compound D-1 with formamide and sodium ethoxide is at a temperature of about 0° C. to about 10° C.
14. The process of claim 1 , wherein the contacting of Compound D-1 with formamide and sodium ethoxide is for about 10 to about 24 hours.
15. A compound
or a salt thereof prepared by the process of claim 1 .