The present invention relates to a process for the preparation of the active pharmaceutical ingredient Fingolimod Hydrochloride (I) and its highly pure intermediate [2-acetamido-2-(acetyloxy methyl)-4-phenylbutyl] acetate(II)

##STR00001##

Phenyl rings provide a robust scaffold for molecular design, given the limited number of ring carbon atoms and the fixed geometry in between. However, it can be difficult to form highly substituted phenyl rings suitable for covalent attachment of multiple moieties thereto. Moreover, binding phenyl rings to a surface in a fixed geometry may be difficult. Hexasubstituted benzenes having certain structural features may alleviate the foregoing difficulties by providing versatile groups for further functionalization and surface attachment. Such hexasubstituted benzenes may have a structure of

##STR00001##

in which each X is independently Cl, Br or N.sub.3, and each Z is independently —CH(Br)CH.sub.3, —CH(N.sub.3)CH.sub.3, —CH═CH.sub.2, —CH.sub.2CH.sub.3, —CH.sub.2CH.sub.2SiR′.sub.3 (R′=hydrocarbyl), or

##STR00002##

Alternating groups in the hexasubstituted benzenes may be directed toward opposite faces of the phenyl ring, such that orthogonal reactive groups are directed toward the opposite faces. Certain groups may facilitate surface attachment of the hexasubstituted benzenes.

Phenyl rings provide a robust scaffold for molecular design, given the limited number of ring carbon atoms and the fixed geometry in between. However, it can be difficult to form highly substituted phenyl rings suitable for covalent attachment of multiple moieties thereto. Moreover, binding phenyl rings to a surface in a fixed geometry may be difficult. Hexasubstituted benzenes having certain structural features may alleviate the foregoing difficulties by providing versatile groups for further functionalization and surface attachment. Such hexasubstituted benzenes may have a structure of

##STR00001##

in which each X is independently Cl, Br or N.sub.3, and each Z is independently —CH(Br)CH.sub.3, —CH(N.sub.3)CH.sub.3, —CH═CH.sub.2, —CH.sub.2CH.sub.3, —CH.sub.2CH.sub.2SiR′.sub.3 (R′=hydrocarbyl), or

##STR00002##

Alternating groups in the hexasubstituted benzenes may be directed toward opposite faces of the phenyl ring, such that orthogonal reactive groups are directed toward the opposite faces. Certain groups may facilitate surface attachment of the hexasubstituted benzenes.

An intermediate of a polyamine derivative, a preparation method therefor, and a use thereof. The intermediate is easy to prepare and high in purity; and when the intermediate is used for preparing the polyamine derivative, the obtained product is high in purity, the operation is simple and convenient, the purity and yield of the polyamine derivative are improved, the purification operation for the product is simplified, and the industrial production of the polyamine derivative and a medicinal salt thereof can be improved. Further provided is a preparation method for the polyamine derivative, the operation thereof is simple and convenient, and the purity of the obtained product is high. The method has a very good application prospect in the field of chemical medicines.

An intermediate of a polyamine derivative, a preparation method therefor, and a use thereof. The intermediate is easy to prepare and high in purity; and when the intermediate is used for preparing the polyamine derivative, the obtained product is high in purity, the operation is simple and convenient, the purity and yield of the polyamine derivative are improved, the purification operation for the product is simplified, and the industrial production of the polyamine derivative and a medicinal salt thereof can be improved. Further provided is a preparation method for the polyamine derivative, the operation thereof is simple and convenient, and the purity of the obtained product is high. The method has a very good application prospect in the field of chemical medicines.

Polymorphic forms of (R)-oxybutynin HCl, including three crystalline forms, are prepared and characterized. Uses of the various polymorphic forms of (R)-oxybutynin HCl for Obstructive Sleep Apnea (OSA) treatment are also disclosed.

Polymorphic forms of (R)-oxybutynin HCl, including three crystalline forms, are prepared and characterized. Uses of the various polymorphic forms of (R)-oxybutynin HCl for Obstructive Sleep Apnea (OSA) treatment are also disclosed.

Phenyl rings provide a robust scaffold for molecular design, given the limited number of ring carbon atoms and the fixed geometry in between. However, it can be difficult to form highly substituted phenyl rings suitable for covalent attachment of multiple moieties thereto. Moreover, binding phenyl rings to a surface in a fixed geometry may be difficult. Hexasubstituted benzenes having certain structural features may alleviate the foregoing difficulties by providing versatile groups for further functionalization and surface attachment. Such hexasubstituted benzenes may have a structure of ##STR00001##
in which each X is independently Cl, Br or N.sub.3, and each Z is independently —CH(Br)CH.sub.3, —CH(N.sub.3)CH.sub.3, —CH═CH.sub.2, —CH.sub.2CH.sub.3, —CH.sub.2CH.sub.2SiR′.sub.3 (R′=hydrocarbyl), or ##STR00002##
Alternating groups in the hexasubstituted benzenes may be directed toward opposite faces of the phenyl ring, such that orthogonal reactive groups are directed toward the opposite faces. Certain groups may facilitate surface attachment of the hexasubstituted benzenes.

Amines and amine derivatives that improve the buffering range, and/or reduce the chelation and other negative interactions of the buffer and the system to be buffered. The reaction of amines or polyamines with various molecules to form polyamines with differing pKa's will extend the buffering range. Derivatives that result in polyamines that have the same pKa yield a greater buffering capacity. Derivatives that result in zwitterionic buffers improve yield by allowing a greater range of stability.

Amines and amine derivatives that improve the buffering range, and/or reduce the chelation and other negative interactions of the buffer and the system to be buffered. The reaction of amines or polyamines with various molecules to form polyamines with differing pKa's will extend the buffering range. Derivatives that result in polyamines that have the same pKa yield a greater buffering capacity. Derivatives that result in zwitterionic buffers improve yield by allowing a greater range of stability.