This invention is directed to asymmetric synthesis of funapide, which is useful for the treatment and/or prevention of sodium channel-mediated diseases or conditions, such as pain.

Organosilicon Lewis acids supported on activated oxides and metal oxo complexes grafted on the organosilicon Lewis acids as heterogeneous catalysts and the related compositions, methods and systems are described. These organosilicon Lewis acids and the grafted metal oxo complexes catalyze industrially important chemical reactions including, respectively, C—F bond activation and olefin metathesis reactions such as homocoupling and polymerizations.

The disclosed embodiments detail improved methods for the synthesis of diketopiperazines from amino acids. In particular improved methods for the cyclocondensation and purification of N-protected 3,6-(aminoalkyl)-2,5-diketopiperazines from N-protected amino acids. Disclosed embodiments describe methods for the synthesis of 3,6-bis-[N-protected aminoalkyl]-2,5-diketopiperazine comprising heating a mixture of an amino acid in the presence of a catalyst in an organic solvent. The catalyst is selected from the group comprising sulfuric acid, phosphoric acid, p-toluenesulfonic acid, 1-propylphosphonic acid cyclic anhydride, tributyl phosphate, phenyl phosphonic acid and phosphorous pentoxide among others. The solvent is selected from the group comprising: dimethylacetamide, N-methyl-2-pyrrolidone, diglyme, ethyl glyme, proglyme, ethyldiglyme, m-cresol, p-cresol, o-cresol, xylenes, ethylene glycol and phenol among others.

Methods for preparing the Bruton's Tyrosine Kinase (“BTK”) inhibitor compound 2-{3′-hydroxymethyl-1-methyl-5-[5-((S)-2-methyl-4-oxetan-3-yl-piperazin-1-yl)-pyridin-2-ylamino]-6-oxo-1,6-dihydro-[3,4′]bipyridinyl-2′-yl}-7,7-dimethyl-3,4,7,8-tetrahydro-2H,6H-cyclopenta[4,5]pyrrolo[1,2-a]pyrazin-1-one are provided. Methods for preparing tricyclic lactam compounds are also provided.

The invention provides compounds of general structure I: (Ar.sup.1—Ar.sup.2—Ar.sup.3-E-P(=D)R.sub.2-).sub.nM.sub.mX.sub.nL.sub.n″. In this structure: •Ar.sup.1, Ar.sup.2 and Ar.sup.3 are aromatic groups wherein: —Ar.sup.1 and Ar.sup.3 are in a 1,3 relationship on Ar.sup.2, —each of Ar.sup.1, Ar.sup.2 and Ar.sup.3 optionally comprises one or more ring substituents of formula YR′.sub.r wherein each Y independently is absent or is O, S, B, N or Si and each R′ is independently H, halogen, alkyl, cycloalkyl, aryl or heteroaryl and r is 1, 2 or 3, where r is 1 if Y is absent or is O or S, 2 if Y is B or N and 3 if Y is Si, —Ar.sup.1, Ar.sup.2 and Ar.sup.3 are each independently carbocyclic or heterocyclic and each is independently monocyclic, bicyclic or polycyclic and each ring of each of Ar.sup.1, Ar.sup.2 and Ar.sup.3 independently has 5, 6 or 7 ring atoms; •E is absent or is selected from the group consisting of O, S, NR″, SiR″.sub.2, AsR″.sub.2 and CR″.sub.2; •M is a complexing metal; •X is selected from the group consisting of H, F, Br, CI, I, OTf, dba (dibenzylidene acetone), OC(═O)CF.sub.3 and OAc; •L is selected from the group consisting of PR″.sub.2, NR″.sub.2, OR″, SR″, SiR″.sub.3, AsR″.sub.3, alkene, alkyne, aryl and heteroaryl, each of said alkene, alkyne, aryl and heteroaryl being optionally substituted, for example with one or more halogens and/or with one or more R groups as defined herein; •each R is independently alkyl, cycloalkyl, heterocyclyl, heterocycloalkyl, aryl or -, heteroaryl; •D is absent or is ═S or —O or —Z-linker-Z—, where each Z independently is O or NH or N-alkyl and linker is an alkyl chain of 2-5 carbon atoms in length; •each R″ is independently H, alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl, each other than H being optionally substituted, or R″.sub.2 is —Z-linker-Z— as defined above; and •m is 0 or 1 or 2; wherein if m is 0, n is 1, n′ and n″ are 0 and -- is absent; and if m is 1 or 2, n is 1 or 2 and n′ and n″ are integers such that the coordination sphere of M is filled, and D is absent.

Processes for separating conjunct polymer from an organic phase are described. A mixture comprising an ionic liquid phase and the organic phase into the ionic phase and an organic phase comprising the conjunct polymer and at least one silyl or boryl compound. The organic phase is separated in a fractionation column into an overhead fraction comprising unreacted silane or borane compound and a bottoms fraction comprising the conjunct polymer and the silyl or boryl compound. The bottoms fraction is passed through an adsorption zone, and the silyl or boryl compound is recovered. Alternatively, the organic phase is passed through an adsorption zone first to remove the conjunct polymer and then a fractionation zone to separate the unreacted silane or borane compound from the silyl or boryl compound.

The present invention discloses recyclable polymeric catalyst of Formula I, for chlorination of organic acids and alcohols using chlorinating agents such as carbonyl chloride, oxalyl chloride or thionyl chloride,

##STR00001##

wherein, ‘m’ on the pendent groups on polystyrene backbone can have values from 1 to 5 and R is the alkyl group ranging from C1 to C5.

A process for the synthesis of Dapsone and intermediates thereof are described.

The present invention is directed to reaction mixtures comprising a water-surfactant mixture, wherein the catalyst comprises a compound with solubilizing groups. This technology improves the solubility of the reaction components in the water-surfactant mixture and thereby, greatly increases the productivity and selectivity of the chemical reaction.

It is an object of the present invention to provide a method for producing a terminal-modified polybutadiene or terminal-modified hydrogenated polybutadiene that does not become colored or white and turbid, without using an organotin compound. The production method of the present invention includes reacting an acrylate or methacrylate represented by formula (I), a diisocyanate compound represented by formula (II), and a polybutadiene or hydrogenated polybutadiene having a hydroxyl group at a polymer terminal, represented by formula (III), in the presence of at least one selected from an organoaluminum compound and an organozinc compound (with the proviso that zinc naphthenate is excluded). ##STR00001##