Abstract: The present invention relates to the process for preparing crystalline forms of Ribociclib succinate (1).
We claim:
1. A process for the preparation of crystalline forms BP-1, BP-1, BP-2, BP-3, BP-4, BP-5 of Ribociclib succinate (1) comprising:
a) Providing Ribociclib succinate (1) in a suitable protic or aprotic solvent or mixtures thereof at 25-30 °C;
b) optionally, heating the reaction mixture at 50-70 °C;
c) optionally, cooling the filtrate to -20 to 35 °C;
d) isolating crystalline forms of Ribociclib succinate (1); and
e) drying the isolated product under suitable conditions.
2. The process of claim 1, wherein the solvent is selected from a group comprising of water, methanol, ethanol, isopropyl alcohol, benzyl alcohol, butyl alcohol, isobutyl alcohol, acetone, acetonitrile, 1,4-dioxane, diethyl ether, dichloromethane, ethyl acetate, n-butyl acetate , N,N-dimethylformamide, methyl tertiary butyl ether, diethyl ether, n-hexane, cyclohexane, toulene, tetrahydrofuran or mixtures thereof.
3. A process for the preparation of crystalline forms BP-6 of Ribociclib succinate (1) comprising of the following steps:
a) Providing Ribociclib free base in a suitable first solvent at 25-30 °C;
b) providing succinic acid in a suitable second solvent at 25-30 °C;
c) heating the reaction mass to a suitable temperature;
d) cooling and filtering the reaction mass;
e) adding the Ribociclib free base solution and succinic acid solution to a suitable third solvent at 25-35°C; and
f) isolating crystalline form BP-6 of Ribociclib succinate (1) using a suitable technique.
4. The process of claim 3, wherein the solvent is selected from a group comprising of water, methanol, ethanol, isopropyl alcohol, benzyl alcohol, butyl alcohol, isobutyl alcohol, acetone, acetonitrile, 1,4-dioxane, diethyl ether, dichloromethane, ethyl acetate, n-butyl acetate , N,N-dimethylformamide, methyl tertiary butyl ether, diethyl ether, n-hexane, cyclohexane, n-heptane, toulene, tetrahydrofuran or mixtures thereof.
5. The process of claim 3, wherein the suitable technique used for isolation of crystalline form is selected from a group comprising of vacuum filtration, centrifugal filtration, gravity filtration, cold filtration, hot filtration, vacuum nutsehe filtration, pressure nutsche filtration.
6. A process for the preparation of crystalline forms BP-7 of Ribociclib succinate (1) comprising:
a) Providing Ribociclib free base in a suitable first solvent at 25-30 °C;
b) heating the reaction mass to a suitable temperature;
c) adding the second solvent to the Ribociclib free base solution at a suitable temperature;
d) adding succinic acid to the reaction solution at a suitable temperature;
e) cooling and filtering the reaction mass; and
f) isolating crystalline form BP-7 of Ribociclib succinate (1) using a suitable technique.
7. The process of claim 6, wherein the suitable solvent is selected from a group comprising of water, methanol, ethanol, isopropyl alcohol, benzyl alcohol , acetone, acetonitrile, nitromethane, 1,4-dioxane, diethyl ether, dichloromethane, 1,4-dioxane, ethyl acetate, n-butyl acetate, N, N-dimethylformamide, methyl tertiary butyl ether, hexane, cyclohexane, toulene, n-heptane, tetrahydrofuran or mixtures thereof.
8. The process of claim 6, wherein the suitable technique used for isolation of crystalline form is selected from a group comprising of air tray dryer, vacuum tray dryer, fluidized bed dryer, spin flash dryer, flash dryer and spray dryer.
| # | Name | Date |
|---|---|---|
| 1 | 201841033501-PROVISIONAL SPECIFICATION [06-09-2018(online)].pdf | 2018-09-06 |
| 2 | 201841033501-FORM 1 [06-09-2018(online)].pdf | 2018-09-06 |
| 3 | 201841033501-DRAWINGS [06-09-2018(online)].pdf | 2018-09-06 |
| 4 | abstract_201841033501 .jpg | 2018-09-10 |
| 5 | Form1_Proof of Right_20-09-2018.pdf | 2018-09-20 |
| 6 | Correspondence by Applicant_Form1_20-09-2018.pdf | 2018-09-20 |
| 7 | 201841033501-FORM 3 [29-08-2019(online)].pdf | 2019-08-29 |
| 8 | 201841033501-ENDORSEMENT BY INVENTORS [29-08-2019(online)].pdf | 2019-08-29 |
| 9 | 201841033501-COMPLETE SPECIFICATION [29-08-2019(online)].pdf | 2019-08-29 |
| 10 | Correspondence by Agent_Form-2, complete, Form-3 And Form-5_03-09-2019.pdf | 2019-09-03 |