Crystalline 4′-epidaunorubicin hydrochloride and use thereof
View Patent ↗4′-epidaunorubicin hydrochloride is provided in a crystalline form which is stable and readily soluble. A process of producing the crystalline form includes crystallizing 4′-epidaunorubicin hydrochloride in a solvent system including (a) solvent A selected from C 1 and C 2 halogenated solvents and mixtures thereof, (b) solvent B selected from C 1 -C 5 straight and branched alcohols and mixtures thereof, and (c) solvent C selected from C 1 -C 5 straight and branched alcohols and mixtures thereof, wherein solvent C is selected to provide lower solubility to 4′-epidaunorubicin hydrochloride than solvent B. A method of producing an anthracycline using crystalline 4′-epidaunorubicin hydrochloride is also provided.
1. A method of producing an anthracycline, the method comprising using crystalline 4′-epidaunorubicin hydrochloride as an intermediate, wherein the crystalline 4′-epidaunorubicin hydrochloride is characterized by its powder X-ray diffraction pattern comprising the following characteristic peaks:
Diffraction Angle 2(theta)
5.13
7.64
12.18
16.77
17.00
19.86
21.82
22.58
23.03.
2. The method according to claim 1 , wherein the crystalline 4′-epidaunorubicin hydrochloride is further characterized by its powder X-ray diffraction pattern comprising the following peaks:
Diffraction Angle
Relative intensity
2(theta)
P(%)
5.13
40.00-46.00
7.64
29.00-33.50
12.18
23.50-26.00
16.77
18.90-20.70
17.00
24.50-26.90
19.86
54.00-62.00
21.82
25.80-28.25
22.58
100
23.03
30.00-32.00.
3. The method according to claim 1 , wherein the anthracycline is epirubicin.
4. The method according to claim 1 , wherein the method comprises a step of dissolving the crystalline 4′-epidaunorubicin hydrochloride in methanol.
5. The method according to claim 3 , wherein the method comprises a step of dissolving the crystalline 4′-epidaunorubicin hydrochloride in methanol.