Crystalline forms of 1-(4-{[6-amino-5-(4-phenoxy-phenyl)-pyrimidin-4-ylamino]-methyl}-piperidin-1-yl)-propenone

Patent metadata

Field	Value
Publication number	US-10464923-B2
Application number	US-201815902482-A
Country	US
Kind code	B2
Filing date	Feb 22, 2018
Priority date	Feb 27, 2017
Publication date	Nov 5, 2019
Grant date	Nov 5, 2019

Abstract

The present invention relates to a solid form of 1-(4-{[6-Amino-5-(4-phenoxy-phenyl)-pyrimidin-4-ylamino]-methyl}-piperidin-1-yl)-propenone, or pharmaceutically acceptable salts thereof, useful as BTK inhibitors.

First claim

We claim:

1. A solid form of compound 1,

wherein said solid form is a crystalline form A2,
wherein said form A2 is characterized by the following 2θ XRPD peaks at 4.7, 9.4, 15.0, 17.5, 17.9, 19.0, 19.7, 20.6 and 23.4±0.2 degrees under the following conditions: monochromatic Cu-Kα 1 radiation, λ=1.5406 Å.

2. A solid form of compound 1,

which is a solid form Malonate-NF1 of a malonate salt of compound 1 characterized by two or more 2θ XRPD peaks at 7.6, 15.6, or 25.0±0.2 degrees under the following conditions: monochromatic Cu-Kα 1 radiation, λ=1.5406 Å.

3. The Malonate-NF1 salt of claim 2 , characterized by four or more 2θ XRPD peaks at 7.6, 12.9, 15.6, 16.2, 20.7, 20.9, 22.4, or 25.0±0.2 degrees.

4. A solid form of compound 1,

which is a solid form Succinate-NF1 of a succinate salt of compound 1 characterized by two or more 2θ XRPD peaks at 6.7, 19.2, or 20.7±0.2 degrees under the following conditions: monochromatic Cu-Kα 1 radiation, λ=1.5406 Å.

5. The Succinate-NF1 salt of claim 4 , characterized by four or more 2θ XRPD peaks at 6.7, 14.7, 15.5, 19.2, 20.7, 21.6, or 21.9±0.2 degrees.

6. A solid form of compound 1,

which is a solid form Oxalate-NF1 of an oxalate salt of compound 1 characterized by two or more 2θ XRPD peaks at 7.5, 17.8, or 19.5±0.2 degrees under the following conditions: monochromatic Cu-Kα 1 radiation, λ=1.5406 Å.

7. The Oxalate-NF1 salt of claim 6 , characterized by four or more 2θ XRPD peaks at 7.5, 9.0, 16.1, 17.3, 17.8, 19.5, 20.3 or 23.8±0.2 degrees.

8. The solid form of claim 1 , characterized as a mixture of crystalline forms A1 and A2;
wherein said crystalline form A1 is characterized by the following 2θ XRPD peaks at 4.8, 9.5, 15.1, 17.4, 18.1, 20.0, and 23.8±0.2 degrees under the following conditions: monochromatic Cu-Kα 1 radiation, λ=1.5406 Å.

9. A pharmaceutical composition, comprising:
a solid form of compound 1 of claim 1 , and
a pharmaceutically acceptable adjuvant, carrier, or vehicle.

10. A method for treating a BTK-mediated disorder in a patient in need thereof, comprising:
administering to said patient a solid form of compound 1 of claim 1 ;
wherein said BTK-mediated disorder is systemic lupus erythematosus (SLE), multiple sclerosis, or rheumatoid arthritis.

11. A solid form of compound 1,

which is a solid form Fumarate-NF1 of a fumarate salt of compound 1 characterized by four or more 2θ XRPD peaks at 6.7, 14.8, 15.2, 16.7, 18.3, 19.3, or 20.8±0.2 degrees under the following conditions: monochromatic Cu-Kα 1 radiation, λ=1.5406 Å.

12. A solid form of compound 1,

which is a solid form Maleate-NF1 of a maleate salt of compound 1 characterized by four or more 2θ XRPD peaks at 10.5, 11.5, 17.9, 18.4, 19.0, 20.3, 20.5, or 24.7±0.2 degrees under the following conditions: monochromatic Cu-Kα 1 radiation, λ=1.5406 Å.

13. A solid form of compound 1,

which is a solid form Citrate-NF1 of a citrate salt of compound 1 characterized by four or more 2θ XRPD peaks at 7.5, 12.1, 13.8, 15.0, 16.3, 17.7, 20.3, or 20.8±0.2 degrees under the following conditions: monochromatic Cu-Kα 1 radiation, λ=1.5406 Å.

Assignees

• Merck Patent Gmbh

Inventors

• Becker Axel
• Poma Marco
• Burini Edoardo
• Saal Christoph
• Theuerkorn Vedad

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61P35/02

  specific for leukemia · CPC title

• C07D401/12 Primary

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

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title

• C07D403/12

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