Thermal Transformations of Compound A Polymorphs

Example 18

a) During heating at 90° C. of Compound A crystal Form I (crystallized from ethyl acetate) the characteristic peaks of Form I decreased (particularly noticeable in solid-state CP/MAS ¹³C NMR spectrum in the regions 14-15, 26-29, 44-46 and 63-66 ppm), whereas those of Compound A crystal Form II increased [diagnostic peaks (15.4, 14.7), (29.1, 25.9), (64.0, 65.7) ppm]. Compound A crystal Form I was completely converted to Compound A crystal Form II in 4 hrs.

b) Crystalline Form I/III Compound A, crystallized from water, was heated at 90° C. for 75 min. Solid-state CP/MAS ¹³C NMR of the product confirmed that crystalline Form I/III was transformed to crystalline Form II (re FIG. 16).

c) Crystalline Form II Compound A was heated at 70° C. for 10 h, then left at room temperature overnight. Solid-state CP/MAS ¹³C NMR of the product confirmed that crystalline Form II was unchanged.