The present invention is directed to methods for the asymmetric synthesis of esketamine. The present invention is further directed to key intermediates in the asymmetric esketamine synthesis. In one embodiment, the invention is an asymmetric synthesis of esketamine comprising the conversion of (S)-2′-chloro-2-methoxy-3,4,5,6-5 tetrahydro-[1,1′-biphenyl]-3-yl carbamate to (S)-2′-chloro-1-isocyanato-6-methoxy-1,2,3,4-tetrahydro-1,1′-biphenyl.

##STR00001##

The present invention is directed to methods for the asymmetric synthesis of esketamine. The present invention is further directed to key intermediates in the asymmetric esketamine synthesis. In one embodiment, the invention is an asymmetric synthesis of esketamine comprising the conversion of (S)-2′-chloro-2-methoxy-3,4,5,6-5 tetrahydro-[1,1′-biphenyl]-3-yl carbamate to (S)-2′-chloro-1-isocyanato-6-methoxy-1,2,3,4-tetrahydro-1,1′-biphenyl.

##STR00001##

The present disclosure relates to compositions and methods related to bicyclo[2.2.1] heptanamine-containing compounds and salts.

The present disclosure relates to compositions and methods related to bicyclo[2.2.1] heptanamine-containing compounds and salts.

Provided is a hydrogenation catalyst for an amide compound, containing hydroxyapatite and platinum and vanadium that are fixed on the hydroxyapatite, 15 to 80% of the surface of the platinum being covered with vanadium. The hydrogenation catalyst can promote a reduction reaction in which an amide compound is converted into an amine compound, can be used under mild conditions, and has such durability that the catalyst can be repeatedly used while retaining a high activity.

Provided is a hydrogenation catalyst for an amide compound, containing hydroxyapatite and platinum and vanadium that are fixed on the hydroxyapatite, 15 to 80% of the surface of the platinum being covered with vanadium. The hydrogenation catalyst can promote a reduction reaction in which an amide compound is converted into an amine compound, can be used under mild conditions, and has such durability that the catalyst can be repeatedly used while retaining a high activity.

Disclosed are compounds of Formulas (I), (II), (III), (IV), and (V): ##STR00001##
and/or a salt thereof, wherein R.sub.1 is —OH or —OP(O)(OH).sub.2, and X.sub.1, X.sub.2, X.sub.3, R.sub.2, R.sub.2a, R.sub.a, R.sub.b, and R.sub.c are defined herein. Also disclosed are methods of using such compounds as selective agonists for G protein-coupled receptor S1P.sub.1, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as autoimmune diseases and vascular disease.

Disclosed are compounds of Formulas (I), (II), (III), (IV), and (V): ##STR00001##
and/or a salt thereof, wherein R.sub.1 is —OH or —OP(O)(OH).sub.2, and X.sub.1, X.sub.2, X.sub.3, R.sub.2, R.sub.2a, R.sub.a, R.sub.b, and R.sub.c are defined herein. Also disclosed are methods of using such compounds as selective agonists for G protein-coupled receptor S1P.sub.1, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as autoimmune diseases and vascular disease.

The present disclosure relates to compositions and methods related to bicyclo[2.2.1] heptanamine-containing compounds and salts.

The present disclosure relates to compositions and methods related to bicyclo[2.2.1] heptanamine-containing compounds and salts.