Process for preparing meropenem trihydrate

Patent metadata

Field	Value
Publication number	US-9328115-B2
Application number	US-201314655875-A
Country	US
Kind code	B2
Filing date	Nov 21, 2013
Priority date	Dec 28, 2012
Publication date	May 3, 2016
Grant date	May 3, 2016

Abstract

Provided is a process for the preparation of meropenem trihydrate in high purity and high yield, including using a dry methanol solvate of meropenem, which can remarkably reduce the amount of residual solvents in the resulting product, thereby obtain meropenem trihydrate in high purity.

First claim

The invention claimed is:

1. A process for preparing a trihydrate form of the compound of Formula 1, which comprises:
(a) dissolving a dry methanol solvate of the compound of Formula 1 in a crystalline form having a power X-ray diffraction spectrum comprising peaks at 8.62, 9.76, 12.17, 12.56, 12.99, 15.23, 16.20, 17.20, 18.33, 19.79, 20.24, 21.34, 22.03, 23.69, 24.54, 25.19, and 26.31 °2θ (±0.2°) in water to obtain a solution;

(b) adding an anti-solvent to the solution obtained from step (a) to form a precipitate; and
(c) isolating the precipitate from the mixture obtained from step (b).

2. The process according to claim 1 , wherein the dry methanol solvate of the compound of Formula 1 is a crystalline form having the powder X-ray diffraction spectrum of FIG. 1 .

3. The process according to claim 1 , wherein the dry methanol solvate of the compound of Formula 1 is obtained by a process comprising:
(i) slurrying the compound of Formula 1 or its hydrate in methanol to form a methanol solvate thereof; and
(ii) filtering the slurry obtained from the step (i), followed by drying the resulting methanol solvate.

4. The process according to claim 3 , wherein the slurrying is performed at −20° C. to 20° C.

5. The process according to claim 3 , wherein the methanol is used in a ratio of 1 ml to 10 ml based on 1 g of the compound of Formula 1 or its hydrate.

6. The process according to claim 1 , wherein the dissolving in the step (a) is performed at 0° C. to 20° C.

7. The process according to claim 6 , wherein the dissolving in the step (a) is performed at 5° C. to 15° C.

8. The process according to claim 1 , further comprising seeding meropenem trihydrate to the solution obtained from the step (a), prior to performing the step (b).

9. The process according to claim 1 , wherein the anti-solvent in the step (b) is isopropyl alcohol, acetone, tetrahydrofuran, or ethanol.

10. The process according to claim 9 , wherein the anti-solvent in the step (b) is isopropyl alcohol.

11. The process according to claim 1 , wherein the step (b) is performed at −20° C. to 20° C.

12. The process according to claim 11 , wherein the step (b) is performed at −10° C. to 5° C.

13. The process according to claim 1 , wherein the step (b) is repeated two or more times.

14. A methanol solvate of the compound of Formula 1 in a crystalline form having a powder X-ray diffraction spectrum comprising peak at 8.62, 9.76, 12.17, 12.56, 12.99, 15.23, 16.20, 17.20, 18.33, 19.79, 20.24, 21.34, 22.03, 23.69, 24.54, 25.19, and 26.31 °2θ (±0.2°):

15. The methanol solvate of the compound of Formula 1 according to claim 14 , which is a crystalline form having the powder X-ray diffraction spectrum of FIG. 1 .

16. The methanol solvate of the compound of Formula 1 according to claim 14 , having the Infrared spectrum of FIG. 4 .

Assignees

• Dae Woong Pharma

Inventors

• Choi Soo-Jin
• Lee Byung-Goo
• Yoon Hee-Kyoon
• Park Sung-Woo
• Jun Sun-Ah
• Lee Kyung-Ho
• Lim Byung-Jo

Classifications

• A61P31/00

  Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics · CPC title

• C07D477/06 Primary

  from compounds already containing the ring or condensed ring systems, e.g. by dehydrogenation of the ring, by introduction, elimination or modification of substituents · CPC title

• C07D487/04 Primary

  Ortho-condensed systems · CPC title

• C07D477/20

  Sulfur atoms · CPC title

• C07D403/12

  linked by a chain containing hetero atoms as chain links · CPC title