Abstract

The present invention relates to an improved process for O-demethylating methoxy substituted morphinan-6-one derivatives using AlCl3 as a demethylating agent in a reaction-inert solvent having a water content ranging from 0.1 %wt to 0.8 %wt.10

IPC Classes  ?

• C07D 489/08 - Oxygen atom

Abstract

(A) reacting the alkali metal salt of 2, 6-dichlorpurine with a 2-desoxy-3, 5 -di-O-p-toluoyl-alpha-D-erythro-pentofuranose or a derivative thereof, in a suitable organic solvent, said reaction optionally being carried out in the presence of a Lewis-acid, whereby a mixture comprising the intermediate N (9) -beta-compound, the N (7) -beta-regio- isomer, and the N (9) -alpha-stereoisomer is formed; (B) isolating from said reaction mixture formed the crude reaction product comprising the intermediate N (9) -beta- compound by a purification method, preferably by precipitation or crystallization, using a suitable organic solvent or a mixture of such organic solvents or a mixture of one or more of such organic solvents with water, without using a chromatographic purification method, and (C) subjecting the isolated intermediate N (9 ) -beta-compound to ammonolysis, where upon the 2 '-deoxyadenosine compound is formed, and (D) precipitating or crystallizing the 2 '-deoxyadenosine compound as formed in step (C) from a suitable organic solvent.

IPC Classes  ?

• C07H 19/173 - Purine radicals with 2-deoxyribosyl as the saccharide radical

Abstract

The invention relates to a method for producing 4-(alkyl)-1-(2-methyl-3-(2,6-dimethylmorpholine)propyl) benzol, in particular for producing 4-(1,1-dimethylpropyl)-1-(2-methyl-3-(2,6-dimethylmorpholine)propyl) benzol (amorolfine), by selectively reducing the corresponding alpha benzyl keto compound using hydrogen in that the corresponding 4-(alkyl)-1-(2-methyl-1-oxo-3-(2,6-dimethylmorpholine)propyl)benzol compound is provided as a salt of a strong acid in a suitable inert solvent and said salt is hydrated using hydrogen in the presence of a suitable catalyst.

IPC Classes  ?

• C07D 295/02 - Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms containing only hydrogen and carbon atoms in addition to the ring hetero elements

Abstract

The invention relates to a method for producing N-phenyl-N-(4-piperidinyl)amide salts, particularly pharmaceutically tolerable addition salts of the compound Remifentanil, in that a compound of the formula (III) is reacted with an acrylic acid alkyl ester of the formula CH2=CH-C(O)-OR: where independently of each other R denotes low-molecular alkyl, preferably (C1-4)alkyl, preferably methyl or ethyl, R1 denotes low-molecular alkyl, preferably (C1-4)alkyl, preferably methyl or ethyl; and HX denotes an inorganic or organic acid, wherein the components are optionally reacted in the presence of a catalyst, preferably at a higher temperature, thereby obtaining the salt of the compound of formula (I).

IPC Classes  ?

• C07D 211/66 - Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals attached in position 4 having a hetero atom as the second substituent in position 4

Abstract

Method of producing 2'-deoxy-5-azacytidine (Decitabine) by providing a com- pound of formula (I), wherein R is a removable substituent known per se; and Rl is a removable substituent; further providing a silylated base of formula (II), wherein R2 is a protecting group, preferably a trimethylsilyl TMS) -residue; reacting the compound of formula (I) and the com- pound of formula (II) together in a suitable anhydrous solvent and in the presence of a suitable catalyst; and removing the substituents R from the compound obtained in order to obtain the com- pound 2'-deoxy-5-azacytidine (Decitabine), characterized in that said catalyst is selected from the group comprising a salt of an aliphatic sulphonic acid or a salt of a strong inorganic acid.

IPC Classes  ?

• C07H 19/12 - Triazine radicals

Abstract

Method of producing 2'-deoxy-5-azacytidine (Decitabine) by providing a compound of formula (I), wherein R is a removable substituent known per se; and R1 is a removable substituent; further providing a silylated base of formula (II), wherein R2 is a protecting group, preferably a trimethylsilyl TMS ) -residue; reacting the compound of formula (I) and the compound of formula (II) together in a suitable anhydrous solvent and in the presence of a suitable catalyst; and removing the substituents R from the compound obtained in order to obtain the compound 2'-deoxy-5-azacytidine (Decitabine), characterized in that said catalyst is selected from the group comprising a salt of an aliphatic sulphonic acid or a salt of a strong inorganic acid.

IPC Classes  ?

• C07H 19/12 - Triazine radicals

Abstract

Method of producing a free nucleoside compound, the compound 2'- deoxy-5-azacytidine (Decitabine) being excluded, by reacting a glycoside donor preferably a 1-halogen derivative, or 1-0-acyl, 1-0-alkyl, or an imidate preferably a trichloromethyl derivative, or a thio-alkyl derivative of a blocked monosaccharide or oligosaccharide preferably ribose and 2-desoxyribose derivatives with a protected nucleoside base, in a suitable anhydrous solvent and in the presence of a catalyst, and removing the protecting groups from said blocked nucleoside compound, wherein said catalyst is selected from the group comprising salts of an aliphatic sulphonic acid and/or salts a strong inorganic acid containing a non-nucleophilic anion.

IPC Classes  ?

• C07H 19/00 - Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radicalNucleosidesMononucleotidesAnhydro derivatives thereof
• C07H 19/06 - Pyrimidine radicals
• C07H 19/12 - Triazine radicals
• C07H 19/16 - Purine radicals

Abstract

Method of producing a free nucleoside compound, the compound 2'- deoxy-5- azacytidine (Decitabine) being excluded, by reacting a glycoside donor preferably a 1-halogen derivative, or 1-0-acyl, 1-0-alkyl, or an imidate preferably a trichloromethyl derivative, or a thio-alkyl derivative of a blocked monosaccharide or oligosaccharide preferably ribose and 2-desoxyribose derivatives with a protected nucleoside base, in a suitable anhydrous solvent and in the presence of a catalyst, and removing the protecting groups from said blocked nucleoside compound, wherein said catalyst is selected from the group comprising salts of an aliphatic sulphonic acid and/or salts a strong inorganic acid containing a non-nucleophilic anion.

IPC Classes  ?

• C07H 19/00 - Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radicalNucleosidesMononucleotidesAnhydro derivatives thereof
• C07H 19/06 - Pyrimidine radicals
• C07H 19/12 - Triazine radicals
• C07H 19/16 - Purine radicals

Abstract

The invention relates to a method for producing n-methylnaltrexone bromide, a compound of the general formula (I), X' meaning an anion that is different from bromide anion, and R meaning hydrogen or a leaving group, being dissolved or dispersed in a suitable polar solvent, said solution or dispersion being mixed with a compound containing bromide anions, and the resulting reaction mixture being stirred until the n-methylnaltrexone bromide is formed and crystallized, wherein, in the case that R means a leaving group, said group is removed during or after the reaction.

IPC Classes  ?

• C07D 489/08 - Oxygen atom
• A61K 31/485 - Morphinan derivatives, e.g. morphine, codeine
• A61P 25/04 - Centrally acting analgesics, e.g. opioids
• A61P 1/10 - Laxatives

Abstract

The invention relates to a method for the production of n-methyl naltrexone bromide, wherein a compound of the general formula (I), in which X- represents an anion that is different from a bromide anion and R represents hydrogen or a nucleofuge, (i) is dissolved or dispersed in a suitable polar solvent, (ii) said solution or dispersion is mixed with a compound containing bromide anions, and (iii) the reaction mixture thus obtained is stirred until the n-methyl naltrexone bromide has formed and crystallized, wherein, (iv) if R represents a nucleofuge, R is removed before, during, or after the conversion.

IPC Classes  ?

• C07D 489/08 - Oxygen atom
• A61K 31/485 - Morphinan derivatives, e.g. morphine, codeine
• A61P 25/04 - Centrally acting analgesics, e.g. opioids
• A61P 1/10 - Laxatives

Abstract

Solvent-free crystalline polymorphic form of naltrexone, characterized in that it has the XRD data listed in Table 1, and a method for the preparation of this polymorphic form; and a method for converting this polymorphic form of naltrexone into a known polymorphic form of naltrexone.

IPC Classes  ?

• C07D 489/08 - Oxygen atom
• A61K 31/485 - Morphinan derivatives, e.g. morphine, codeine
• A61P 25/30 - Drugs for disorders of the nervous system for treating abuse or dependence

Abstract

A process for purifying plant extracts which consist essentially of noroxymorphone compounds and which comprise, as impurities, .alpha.,.beta.-unsaturated noroxymorphone compounds, by (a) converting the plant extract or the product of a subsequent stage in the synthesis of a selected noroxymorphone compound in a reaction which converts the hydroxyl groups present in the mixture to leaving groups of the formula -OR2 in which R2 is the introduced radical of the leaving group, (b) these leaving groups are optionally detached again, then (c) the resulting mixture is subjected to a selective hydrogenation, so that a saturated bond is formed in the .alpha.,.beta.-position of the unsaturated noroxymorphone compounds and any remaining leaving groups are each converted to a hydroxyl group and then optionally (d) the pure noroxymorphone compound is isolated; processing of the noroxymorphone purified in this way to naltrexone or naloxone or a salt of these compounds or a quaternary derivative of these compounds; pharmaceutical formulations comprising such a compound.

IPC Classes  ?

• C07D 489/08 - Oxygen atom
• A61K 31/00 - Medicinal preparations containing organic active ingredients