An improved and well reproducible process for the preparation of Enclomiphene citrate having needle shaped crystal habit is provided. It is also related to a solid form of Enclomiphene citrate.

An improved and well reproducible process for the preparation of Enclomiphene citrate having needle shaped crystal habit is provided. It is also related to a solid form of Enclomiphene citrate.

The present disclosure provides industrially scalable methods of making (Z)-endoxifen or a salt thereof, crystalline forms of endoxifin, and compositions comprising them. The present disclosure also provides methods for treating hormone-dependent breast and hormone-dependent reproductive tract disorders.

The present disclosure provides industrially scalable methods of making (Z)-endoxifen or a salt thereof, crystalline forms of endoxifin, and compositions comprising them. The present disclosure also provides methods for treating hormone-dependent breast and hormone-dependent reproductive tract disorders.

The present disclosure generally relates to compounds useful as immunomodulators. Provided herein are compounds, compositions comprising such compounds, and methods of their use. The disclosure further pertains to pharmaceutical compositions comprising at least one compound according to the disclosure that are useful for the treatment of various diseases, including cancer and infectious diseases.

The present disclosure generally relates to compounds useful as immunomodulators. Provided herein are compounds, compositions comprising such compounds, and methods of their use. The disclosure further pertains to pharmaceutical compositions comprising at least one compound according to the disclosure that are useful for the treatment of various diseases, including cancer and infectious diseases.

Disclosed is a process for preparing (Z)-endoxifen, comprising (i) recrystallizing an input crystalline solid comprising a mixture of (Z)-endoxifen (1) and (E)-endoxifen (2) from a first solvent to provide a first crystalline solid and a first mother liquor, wherein the first mother liquor has a ratio of (1) to (2) at least 1.3 times greater than the ratio in the input crystalline solid (1) and (2); (ii) recrystallizing a solid produced by concentrating the first mother liquor, or by removal of the first solvent from the first mother liquor, from a second solvent to give a second crystalline solid and a second mother liquor; (iii) optionally recrystallizing the second crystalline solid from the second solvent one to five additional times to give a third crystalline solid; wherein the third crystalline solid has a ratio of (Z)-endoxifen (1) to (E)-endoxifen (2) greater than 20:1.

##STR00001##

Disclosed is a process for preparing (Z)-endoxifen, comprising (i) recrystallizing an input crystalline solid comprising a mixture of (Z)-endoxifen (1) and (E)-endoxifen (2) from a first solvent to provide a first crystalline solid and a first mother liquor, wherein the first mother liquor has a ratio of (1) to (2) at least 1.3 times greater than the ratio in the input crystalline solid (1) and (2); (ii) recrystallizing a solid produced by concentrating the first mother liquor, or by removal of the first solvent from the first mother liquor, from a second solvent to give a second crystalline solid and a second mother liquor; (iii) optionally recrystallizing the second crystalline solid from the second solvent one to five additional times to give a third crystalline solid; wherein the third crystalline solid has a ratio of (Z)-endoxifen (1) to (E)-endoxifen (2) greater than 20:1.

##STR00001##

1,7-diaryl-1,6-heptadiene-3,5-dione derivatives, methods for the production and use thereof.

The present disclosure provides industrially scalable methods of making (Z)-endoxifen or a salt thereof, crystalline forms of endoxifen, and compositions comprising them. The present disclosure also provides methods for treating hormone-dependent breast and hormone-dependent reproductive tract disorders.