Synthesis of a compound that modulates kinases
The present disclosure provides processes for the preparation of a compound of formula I: or a salt thereof, active on the receptor protein kinases c-Kit and/or c-Fms and/or Flt3. The disclosure also provides compounds and processes for the preparation of the compounds that are synthetic intermediates to the compound of formula I.
1. A process of preparing a crystalline form of Compound II:
comprising:
(1) adding Compound II to from about 0.4% v/v wet methyl tert-butyl ether (MTBE) to about 1.5% v/v wet MTBE to provide a reaction mixture;
(2) refluxing the reaction mixture;
(3) cooling the reaction mixture to about room temperature; and
(4) isolating the crystalline form of Compound II from the reaction mixture.
2. The process according to claim 1 , wherein step (1) comprises adding Compound II to about 0.5% v/v wet methyl tert-butyl ether (MTBE) to provide the reaction mixture.
3. The process according to claim 2 , wherein step (2) further comprises heating the reaction mixture to a temperature of about 52-53° C.
4. The process according to claim 3 , wherein the crystalline form of compound II is characterized by an X-ray powder diffractogram (XRPD) comprising peaks (±0.2°) at 7.1, 16.5, 20.8, 23.2 and 28.1 °2θ as determined on a diffractometer using Cu-Ka radiation.