摘要:
A method is described for the preparation of aryl-pyridine compounds of formula (I) by cross-coupling reaction, promoted by catalytic systems based on palladium or nickel between compounds of formula (II) and (III) in which:—Met represents Mg or Zn,—Y represents Cl, Br, I or acetoxy,—Z represents I, Br, Cl, triflate, sulphonate, phosphate,—R1, R2, R3, R4, which are the same as one another or different, represent hydrogen, a linear and/or branched C1-C4 alkyl, and/or an aryl, and/or a heteroaryl, or R1 and R2 and/or R3 and R4, taken together, form a C3-C8 ring, an aryl and/or a heteroaryl,—A represents —COR5 where R5 represents hydrogen, a linear and/or branched C1-C4 alkyl, and/or an aryl, and/or a heteroaryl, or—A represents —CRs5(OR6)(OR7) where R5 has the meaning described above and R6 and R7, which are the same as one another or different, represent a linear and/or branched C1-C4 alkyl, and/or an aryl, and/or a heteroaryl, or R6 and R7, joined together, represent a C1-C8 alkyl or alkenyl.
摘要:
A method is described for the preparation of aryl-pyridine compounds of formula (I) by cross-coupling reaction, promoted by catalytic systems based on palladium or nickel between compounds of formula (II) and (III) in which: -Met represents Mg or Zn, —Y represents Cl, Br, I or acetoxy, —Z represents I, Br, Cl, triflate, sulphonate, phosphate, —R1, R2, R3, R4, which are the same as one another or different, represent hydrogen, a linear and/or branched C1-C4 alkyl, and/or an aryl, and/or a heteroaryl, or R1 and R2 and/or R3 and R4, taken together, form a C3-C8 ring, an aryl and/or a heteroaryl, -A represents —COR5 where R5 represents hydrogen, a linear and/or branched C1-C4 alkyl, and/or an aryl, and/or a heteroaryl, or -A represents —CRs5(OR6)(OR7) where R5 has the meaning described above and R6 and R7, which are the same as one another or different, represent a linear and/or branched C1-C4 alkyl, and/or an aryl, and/or a heteroaryl, or R6 and R7, joined together, represent a C1-C8 alkyl or alkenyl.
摘要:
The invention relates to a new process for the production and/or purification of the salt of the compound (S)-2-[4-(2-fluorobenzyloxy)benzylamino]propanamide, i.e. ralfinamide, or the respective R-enantiomer, with methanesulfonic acid in high yields and very high enantiomeric and chemical purity in the form of the crystalline anhydrous polymorph identified as form A, wherein said salt is substantially free from impurities having genotoxic effect, such as (C1-C5)alkanylmethanesulfonates, and residual solvents known as potential precursors thereof, such as (C1-C5)alkanols or esters thereof with lower alkanoic acids.The process foresees (i) production and/or crystallization of the salt, from water, acetone, an aliphatic ketone of 4-5 carbon, atoms or mixtures thereof with water, or (ii) slurring the solid salt with (a) water, (b) a mixture of water with acetone or an aliphatic ketone of 4-5 carbon atoms, (c) acetone, an aliphatic ketone of 4-5 carbon atoms or a mixture thereof, or (iii) exposure of the solid salt to air stream having high degree of relative humidity, and, when the obtained product consists as a whole or in part of crystalline hemihydrate pseudopolymorph form H crystals, converting said product into anhydrous form A crystals by submitting it to water removal.The crystalline hemihydrate pseudopolymorph form H of ralfinamide methanesulfonate, or its R-enantiomer, is a useful intermediate for obtaining the crystalline anhydrous polymorph A free from the above impurities having genotoxic effect and/or residual solvents known as precursors thereof, and exhibits a physicochemical profile conferring significant advantages in the design and development of solid dosage forms, in particular, of modified release formulations.
摘要:
A process is described for the preparation of arylpyridine compounds by aryl-aryl cross-coupling reactions between a halopyridine and an arylmagnesium halide carried out in the presence of a catalytic amount of a zinc salt and a catalytic amount of palladium. The zinc salt is preferably selected from ZnCl2, ZnBr2 and/or Zn(OAc)2, while the palladium is preferably used in the form of Pd(PPh3)4 or Pd(OAc)2 +4 PPh3. The reaction can also be carried out in the presence of bidentate phosphines, such as, for example, 1,3-bis(diphenylphosphine)propane or 1,4-bis(diphenylphosphine)-butane. It is thus possible to obtain molar yields higher than 97% (calculated relative to the halopyridine) and a catalyticity of more than 2000.
摘要:
A process for the direct and regioselective functionalization of phenothiazine which allows one to introduce an SH group in position 2, said process comprising the sulfination or sulfonation of the phenothiazine N-protected with an alkoxycarbonyl, an alkylsulfonyl or an arylsulfonyl group, the reduction of the produce obtained to give the N-protected 2-mercapto-phenothiazine, and the deprotection of the nitrogen atom. The thus-obtained 2-mercapto-phenothiazine is an important intermediate for the preparation of pharmacological active compounds.
摘要:
Compounds of formula ##STR1## (wherein Ar, R, R.sub.1 and X have the meaning reported in the description) are useful intermediates for the preparation of a variety of organic compounds, also optically active, like alpha-haloketones, alpha-hydroxyketones or ketals, alpha-arylalkanoic acids.
摘要:
A process is described for the preparation of mono (2-ammonium-2-hydroxymethyl-1,3-propanediol) (2R,cis)-1,2-epoxypropyl-phosphonate with improved characteristics of stability, of processing for the preparation of pharmaceutical forms and of stability of the pharmaceutical forms that contain it.
摘要:
A stereoselective process is described for preparing optically active alpha,beta-disubstituted carbonyl compounds, comprising forming an acetal between an alpha,beta-unsaturated aldehyde or ketone and tartaric acid or a derivative thereof, halogenating the product thus obtained, and restoring the carbonyl compound.
摘要:
A new enantioselective process is described for preparing optically active alpha-arylalkanoic acids by:(a) halogenation on the aliphatic carbon atom alpha to the ketal group, of ketals of formula ##STR1## in which Ar represents an aryl, optionally substituted;R represents a C.sub.1 -C.sub.4 alkyl;R.sub.1 and R.sub.2, represent a hydroxy, a O.sup.- M.sup.+, OR.sub.3 or NR.sub.4 R.sub.5 group;the carbon atoms indicated by an asterisk both simultaneously are in (R) or (S) configuration. This reaction is diastereoselective, so that a mixture of alpha-haloketals is obtained in which one of the two epimers prevails, and generally strongly prevails, over the other.(b) rearrangement of the haloketals of formula ##STR2## in which X is Cl, Br or I to alpha-arylalkanoic acids in a single stage or in two successive stages, by way of esters of formula ##STR3## The compounds (A) and (C) are all new compounds. The rearrangement step (b) may be performed under new, inventive conditions. The esters of formula (C) have pharmacological activity analogous to that of the corresponding alpha-arylalkanoic acids.
摘要:
A process is described for the preparation of alpha-hydroxyl-alkanoic acids of formula ##STR1## which are known anti-inflammatory agents or intermediates for known pharmaceutical products. The process consists essentially in the rearrangement of phenolates of formula ##STR2## wherein Ar is an unsubstituted or substituted phenyl or naphthyl, in aqueous environment or in an organic medium, at temperatures comprised within the range of from 0.degree. to 100.degree. C. and within short times, followed by either acid or alkaline hydrolysis.