Polymorphic forms and co-crystals of a c-Met inhibitor

Patent metadata

Field	Value
Publication number	US-10344041-B2
Application number	US-201815966157-A
Country	US
Kind code	B2
Filing date	Apr 30, 2018
Priority date	Apr 17, 2014
Publication date	Jul 9, 2019
Grant date	Jul 9, 2019

Abstract

Provided herein are novel polymorphic forms and co-crystals of a compound useful in the treatment, prevention, or amelioration of cancer. In particular, the invention provides polymorphs and co-crystals of 6-{(1R)-1-[8-fluoro-6-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[4,3-a]pyridin-3-yl]ethyl}-3-(2-methoxyethoxy)-1,6-naphthyridin-5(6H)-one, which is an inhibitor of c-Met.

First claim

We claim:

1. A free base form of 6-{(1R)-1-[8-fluoro-6-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[4,3-a]pyridin-3-yl]ethyl}-3-(2-methoxyethoxy)-1,6-naphthyridin-5(6H)-one, wherein the free base form is selected from the group consisting of an acetone solvate form and a dimethylsulfoxide (DMSO) hemisolvate form.

2. The free base form of claim 1 , wherein the free base form is the acetone solvate form.

3. The free base form of claim 2 , wherein the acetone solvate form comprises about a 1:1 molar ratio of acetone to 6-{(1R)-1-[8-fluoro-6-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[4,3-a]pyridin-3-yl]ethyl}-3-(2-methoxyethoxy)-1,6-naphthyridin-5(6H)-one.

4. The free base form of claim 2 , wherein the acetone solvate form is characterized by an X-ray powder diffraction pattern comprising peaks at about 7.2, 15.5, 17.1, 22.0, and 23.1±0.2° 20 using Cu Kα radiation.

5. A method of preparing an acetone solvate form of 6-{(1R)-1-[8-fluoro-6-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[4,3-a]pyridin-3-yl]ethyl}-3-(2-methoxyethoxy)-1,6-naphthyridin-5(6H)-one, the method comprising preparing a slurry of a monohydrate form of 6-{(1R)-1-[8-fluoro-6-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[4,3-a]pyridin-3-yl]ethyl}-3-(2-methoxyethoxy)-1,6-naphthyridin-5(6H)-one in acetone, and isolating the resulting solid.

6. The free base form of claim 1 , wherein the free base form is the DMSO hemisolvate form.

7. The free base form of claim 6 , wherein the DMSO hemisolvate form comprises about a 1:2 molar ratio of DMSO to 6-{(1R)-1-[8-fluoro-6-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[4,3-a]pyridin-3-yl]ethyl}-3-(2-methoxyethoxy)-1,6-naphthyridin-5(6H)-one.

8. The free base form of claim 6 , wherein the DMSO hemisolvate form is characterized by an X-ray powder diffraction pattern comprising peaks at about 7.3, 13.9, 14.3, 16.2, and 27.8±0.2° 2θ using Cu Kα radiation.

9. A method of preparing a DMSO hemisolvate form of 6-{(1R)-1-[8-fluoro-6-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[4,3-a]pyridin-3-yl]ethyl}-3-(2-methoxyethoxy)-1,6-naphthyridin-5(6H)-one, the method comprising preparing a slurry of the monohydrate form of 6-{(1R)-1-[8-fluoro-6-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[4,3-a]pyridin-3-yl]ethyl}-3-(2-methoxyethoxy)-1,6-naphthyridin-5(6H)-one in DMSO, and isolating the resulting solid.

Assignees

• Amgen Inc

Inventors

• Bauer David
• Bio Matthew
• Cooke Melanie
• Copeland Katrina W
• Peterson Matthew
• Potashman Michele
• Shimanovich Roman
• Tan Helming

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• C07D519/00 Primary

  Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00 · CPC title

• C07D471/04 Primary

  Ortho-condensed systems · CPC title

• A61K31/52

  Purines, e.g. adenine · CPC title

• A61K31/4375

  the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine · CPC title