Process for preparing topotecan

A process for preparing topotecan or a salt thereof, comprising hydrogenating camptothecin in the presence of a hydrogenation catalyst and about 0.001 to about 0.1 molar equivalents of thioanisole per molar equivalent of camptothecin, to form 10-hydroxy camptothecin, reacting 10-hydroxy camptothecin with dimethylamine and about 1 to about 3 equivalents of formaldehyde, per equivalent of 10-hydroxy camptothecin, in the presence of acetic acid to form topotecan acetate, and reacting topotecan acetate with hydrochloric acid, to form topotecan hydrochloride.

Crystalline topotecan hydrochloride having an X-ray power diffraction pattern comprising characteristic peaks at about 7.9, 24.0, 25.0, and 27.9 ±0.2 degrees 2 theta.

Crystalline topotecan hydrochloride Form II having an X-ray powder diffraction pattern substantially as shown in FIG. 4.

Crystalline topotecan hydrochloride Form II having an X-ray power diffraction pattern comprising characteristic peaks at about 7.4, 7.9, 10.1, 19.7, 24.0, 25.0, 25.9, 27.1, and 27.9 ±0.20 degrees 2θ.

Crystalline topotecan hydrochloride having an X-ray power diffraction pattern comprising characteristic peaks at about 12.1 and 23.5 ±0.2 degrees 2 theta.

Crystalline topotecan hydrochloride Form I having an X-ray power diffraction pattern substantially as shown in FIG. 1.

Crystalline topotecan hydrochloride Form I having an X-ray power diffraction pattern comprising characteristic peaks at about 6.1,12.1, 14.2, 22.9, 23.5, and 26.8 ±0.20 degrees 2θ.