The present disclosure is concerned with piperazine-2,5-diones that are capable of inhibiting TGF-β and methods of treating cancers such as, for example, multiple myeloma and a hematologic malignancy, and methods of treating fibrotic conditions using these compounds. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

The present disclosure is concerned with piperazine-2,5-diones that are capable of inhibiting TGF-β and methods of treating cancers such as, for example, multiple myeloma and a hematologic malignancy, and methods of treating fibrotic conditions using these compounds. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Disclosed embodiments relate to improved methods for the synthesis of activated fumarate intermediates and their use in chemical synthesis. Disclosed embodiments describe the synthesis of activated fumarate esters including those derived from activating groups including: 4-nitrophenyl, diphenylphophoryl azide, pivaloyl chloride, chlorosulfonyl isocyanate, p-nitrophenol, MEF, trifluoroacetyl and chlorine, for example, ethyl fumaroyl chloride and the subsequent use of the activated ester in situ. Further embodiments describe the improved synthesis of substituted aminoalkyl-diketopiperazines from unisolated and unpurified intermediates allowing for improved yields and reactor throughput.

Disclosed embodiments relate to improved methods for the synthesis of activated fumarate intermediates and their use in chemical synthesis. Disclosed embodiments describe the synthesis of activated fumarate esters including those derived from activating groups including: 4-nitrophenyl, diphenylphophoryl azide, pivaloyl chloride, chlorosulfonyl isocyanate, p-nitrophenol, MEF, trifluoroacetyl and chlorine, for example, ethyl fumaroyl chloride and the subsequent use of the activated ester in situ. Further embodiments describe the improved synthesis of substituted aminoalkyl-diketopiperazines from unisolated and unpurified intermediates allowing for improved yields and reactor throughput.

Provided herein are dUTPase inhibitors, compositions comprising such compounds and methods of using such compounds and compositions.

Provided herein are dUTPase inhibitors, compositions comprising such compounds and methods of using such compounds and compositions.

The invention provides heterocyclic compounds with quaternary centers and methods of preparing compounds. Methods include the method for the preparation of a compound of Formula (II):

##STR00001##

comprising treating a compound of Formula (I):

##STR00002##

with a transition metal catalyst and under alkylation conditions as valence and stability permit.

The invention provides heterocyclic compounds with quaternary centers and methods of preparing compounds. Methods include the method for the preparation of a compound of Formula (II):

##STR00001##

comprising treating a compound of Formula (I):

##STR00002##

with a transition metal catalyst and under alkylation conditions as valence and stability permit.

The present disclosure provides a process for preparation of 3,6-dichlorocyano pyrazine, 3,6-dioxopiperizine derivatives and production of favipiravir via ammonia or amine-mediated cyclization and chlorination using POCl3 in the presence of pyridine or PCl5. [Formula] wherein in 3,6-dioxopiperazine derivatives (III), X is CN, CONH2 or COOR2′, R1, R2 and R2′ are individually selected from H, C1-C12 alkyl, COOR3 and SO2R3 wherein R3 is substituted or unsubstituted linear or branched lower alkyl.

##STR00001##

The present disclosure provides a process for preparation of 3,6-dichlorocyano pyrazine, 3,6-dioxopiperizine derivatives and production of favipiravir via ammonia or amine-mediated cyclization and chlorination using POCl3 in the presence of pyridine or PCl5. [Formula] wherein in 3,6-dioxopiperazine derivatives (III), X is CN, CONH2 or COOR2′, R1, R2 and R2′ are individually selected from H, C1-C12 alkyl, COOR3 and SO2R3 wherein R3 is substituted or unsubstituted linear or branched lower alkyl.

##STR00001##