Provided herein are intermediates and processes useful for facile synthesis of compounds of Formula 2: ##STR00001##
wherein R.sup.1 is C(O)R.sup.2; R.sup.2 is alkyl optionally substituted with 1-5 halogens; G is phenyl or a 5-6 membered heteroaryl optionally substituted with 1-2 R.sup.3; and each R.sup.3 is independently C.sub.1-C.sub.6 alkyl, CN, C.sub.1-C.sub.6 alkyl-CN, 3-6 membered cycloalkyl, or 4-6 membered heterocycloalkyl.

The present invention provides a process of producing a trifluoromcthoxylated aryl or trifluoromothoxylated heteroaryl having the structure: ##STR00001##
wherein
A is an aryl or heteroaryl, each with or without substitution; and
R.sub.1 is —H, -(alkyl), -(alkenyl), -(alkynyl), -(aryl), -(heteroaryl), -(alkylaryl), -(alkylheteroaryl), —NH-(alkyl), —N(alkyl).sub.2, —NH-(alkenyl), —NH-(alkynyl) —NH-(aryl), —NH-(heteroaryl), —O-(alkyl), —O-(alkenyl), —O-(alkynyl), —O-(aryl), —O-(heteroaryl), —S-(alkyl), —S-(alkenyl), —S-(alkynyl), —S-(aryl), or —S-(heteroaryl), comprising:
(a) reacting a compound having the structure: ##STR00002##
with a trifluoromethylating agent in the presence of a base in a first suitable solvent under conditions to produce a compound having the structure: ##STR00003##
and
(b) maintaining the compound produced in step (a) in a second suitable solvent under conditions sufficient to produce the trifluoromethoxylated aryl or trifluormethoxylated heteroaryl having the structure: ##STR00004##

The present invention provides a process of producing a trifluoromcthoxylated aryl or trifluoromothoxylated heteroaryl having the structure: ##STR00001##
wherein
A is an aryl or heteroaryl, each with or without substitution; and
R.sub.1 is —H, -(alkyl), -(alkenyl), -(alkynyl), -(aryl), -(heteroaryl), -(alkylaryl), -(alkylheteroaryl), —NH-(alkyl), —N(alkyl).sub.2, —NH-(alkenyl), —NH-(alkynyl) —NH-(aryl), —NH-(heteroaryl), —O-(alkyl), —O-(alkenyl), —O-(alkynyl), —O-(aryl), —O-(heteroaryl), —S-(alkyl), —S-(alkenyl), —S-(alkynyl), —S-(aryl), or —S-(heteroaryl), comprising:
(a) reacting a compound having the structure: ##STR00002##
with a trifluoromethylating agent in the presence of a base in a first suitable solvent under conditions to produce a compound having the structure: ##STR00003##
and
(b) maintaining the compound produced in step (a) in a second suitable solvent under conditions sufficient to produce the trifluoromethoxylated aryl or trifluormethoxylated heteroaryl having the structure: ##STR00004##

Fosnetupitant chloride hydrochloride having improved stability, characterized by the following chemical structure: ##STR00001##

The invention provides novel 6-aryl or 6-heteroaryl 4-morpholin-4-yl-pyhdine-2-one compounds of formula (I), pharmaceutical compositions containing such compounds, and methods for using such compounds in treatment of diseases including cancer, diabetes, inflammatory diseases, neurodegenerative disorders, cardiovascular disorders and viral infections; wherein R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are as defined in the specification.

##STR00001##

Disclosed are a process for preparing new crystal salt forms of sulfasalazine, in particular crystal Form A of the D(−)-N-methylglucamine (meglumine) salt of sulfasalazine (see FIG. 1), crystal form A of the piperazine salt of sulfasalazine (see FIG. 2) and crystal Form B of the diethylamine salt of sulfasalazine (see FIG. 4), and a pharmaceutical composition containing one or more of the inventive crystal salt forms in particular in the treatment of a disease or condition in which modulation of inflammatory cells is beneficial, a disease or condition concerning bones or joints and/or the gastro-intestinal tract.

Disclosed are a process for preparing new crystal salt forms of sulfasalazine, in particular crystal Form A of the D(−)-N-methylglucamine (meglumine) salt of sulfasalazine (see FIG. 1), crystal form A of the piperazine salt of sulfasalazine (see FIG. 2) and crystal Form B of the diethylamine salt of sulfasalazine (see FIG. 4), and a pharmaceutical composition containing one or more of the inventive crystal salt forms in particular in the treatment of a disease or condition in which modulation of inflammatory cells is beneficial, a disease or condition concerning bones or joints and/or the gastro-intestinal tract.

Provided herein are small molecule inhibitors for the targeting or IRE1 protein family members. Binding may be direct or indirect. Further provided herein are methods of using IRE1 small molecule inhibitors for use in treating or ameliorating cancer in a subject. Moreover, IRE1 small molecule inhibitors described herein are for the treatment of cancer, where the cancer is a solid or hematologic cancer.

Provided herein are small molecule inhibitors for the targeting or IRE1 protein family members. Binding may be direct or indirect. Further provided herein are methods of using IRE1 small molecule inhibitors for use in treating or ameliorating cancer in a subject. Moreover, IRE1 small molecule inhibitors described herein are for the treatment of cancer, where the cancer is a solid or hematologic cancer.

The present invention relates to novel compounds having anti-cancer activity, methods of making these compounds, and their use for treating cancer and drug-resistant tumors, e.g. melanoma, metastatic melanoma, drug resistant melanoma, prostate cancer and drug resistant prostate cancer.