Abstract

The present invention provides an efficient and improved process for the preparation of Lisdexamphetamine and its pharmaceutically acceptable salts. The process involves the conversion of 1-norephedrine to (2S)-2-amino-l -phenylpropane via a chiral intermediate, (4S, 5R)-4-Methyl-5-Phenyl-2-oxazolidinone, synthesized by treating 1-norephedrine with dimethyl carbonate in the presence of alkali alkoxides, such as sodium methoxide. (2S)-2- amino-1 -phenylpropane is then coupled with amine- and hydroxyl-protected L-Lysine, specifically Di-Boc-L-Lysine-p-nitrophenyl ester (Di-Boc-L-Lysine-ONP) and/or Di-Boc L-lysine OSu., to form Lisdexamphetamine. The process concludes with deprotection and conversion to pharmaceutically acceptable salts. The invention offers advantages such as high yield, improved purity, and scalability, making it cost-effective and suitable for large- scale pharmaceutical manufacturing. Additionally, the use of specific protection groups, including Boc for amines and p-nitrophenol for hydroxyls, ensures efficient coupling and synthesis. The described process is ideal for producing Lisdexamphetamine for therapeutic applications.

IPC Classes  ?

• C07C 271/10 - Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
• C07C 231/14 - Preparation of carboxylic acid amides by formation of carboxamide groups together with reactions not involving the carboxamide groups
• C07C 231/02 - Preparation of carboxylic acid amides from carboxylic acids or from esters, anhydrides, or halides thereof by reaction with ammonia or amines
• C07C 269/04 - Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups the nitrogen atom not being part of nitro or nitroso groups from amines with formation of carbamate groups

Abstract

The invention relates to method for preparation of pure enantiomers of 1-(1-naphthyl)ethyl amine by preparing lactate salt with chiral lactic acid as resolving agent. The method comprises reaction of L-lactic acid or D-lactic acid with racemic 1-(1-naphthyl)ethyl amine to form diastereomeric salts of (R/S)-1-(1-naphthyl)ethyl amine-(D/L)-lactate from which pure enantiomer is isolated. The invention also comprises method for preparation of compound with enriched enantiomers of 1-(1-naphthyl)ethyl amine from the mother liquor separated from the diastereomeric lactate salt. The enriched enantiomer is reacted with pure enantiomers of mandelic acid or lactic acid, preferably D-mandelic acid or L-mandelic acid and converted to diastereomeric mandelate salt. Pure (R)- or (S)-1-(1-naphthyl)ethyl amine is obtained from the diastereomeric mandelate salt. The chiral purity of pure enantiomer obtained is between 99% and 100%.

IPC Classes  ?

• C07C 211/30 - Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing at least one six-membered aromatic ring the six-membered aromatic ring being part of a condensed ring system formed by two rings

Abstract

The invention involves condensation of various derivatives of cyclic alkene alcohols of Formula (II) or Formula (III) where, R1is alkyl, aryl, alkyl aryl or heterocyclic carbamoyl. R2is either R1as mentioned earlier or an acyl group, -C(=O)-R3where, R311212 alkyl, (subst)aryl, alkyl aryl with olivetol to get (-)-trans-∆9-tetrahydrocannabinol (also known as Dronabinol, Formula (I)). The process disclosed provides high purity of dronabinol at crude stage making it easy for purification.

IPC Classes  ?

• C07D 311/78 - Ring systems having three or more relevant rings
• C07D 311/80 - DibenzopyransHydrogenated dibenzopyrans

Abstract

The present invention relates to a process for preparation of dexmethylphenidate hydrochloride from racemic methylphenidate. The process involves the treatment of racemic mixture of dl-throe-methylphenidate base in the presence of di-pivaloyl-D-tartaric acid (D-DPTA) in a solvent to isolate dipivaloyl tartrate salt of d-threo-methylphenidate. The dipivaloyl tartrate salt of d-threo-methylphenidate is treated with a base to obtain a d-threo-methylphenidate base, which is extracted using a suitable solvent. The d-threo-methylphenidate base is treated with hydrochloric acid-isopropyl alcohol solution to obtain slurry of d-threo-methylphenidate hydrochloride also known as dexmethylphenidate hydrochloride. The dexmethylphenidate hydrochloride slurry is filtered and washed with acetone. The invention also discloses a process for recovery of D-DPTA from the salt mother liquor and from the spent aqueous layer. The process is economical, environmental friendly and results in increased yield and optically pure dexmethylphenidate hydrochloride.

IPC Classes  ?

• C07D 211/34 - Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals

Abstract

A method for the preparation of β-amino alcohol of formula (III) in which R1 is Ph, (substituted) Ph, R2 is C1-8 alkyl or C4-6 cyclo alkyl, R3 = R4R5CHNH2 where, R4 = H, C1-8 alkyl, C4-6 cyclo alkyl, or - COOR6 (R6=C1-C8 alkyl); R5 = (subst) aryl], the method including subjecting an α-hydroxy ketone of formula (I) in which R1 and R2 are as defined above is reacted with a chiral amine of formula R3NH2 where R3 = R4R5CH- where, R4 = H, C1-8 alkyl, C4-6 cycloalkyl, or - COOR6 (R6=C1-8 alkyl), R5 = (subst) aryl] to produce a compound of formula (II) in which R1, R2 and R3 are as defined above, followed by reduction to form the compound of formula (III).

IPC Classes  ?

• C07C 213/02 - Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton by reactions involving the formation of amino groups from compounds containing hydroxy groups or etherified or esterified hydroxy groups
• C07C 215/02 - Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton

Abstract

The present invention relates to method of production of optically active chiral amine from alpha hydroxy ketone using enzyme transaminase as the biocatalyst. In particular the present invention relates to productionof (1R, 2S)-Norephedrine and its salts from R-Phenylacetylcarbinol (R- PAC) by employing S-transaminase as the biocatalyst and Isopropylamine as the amine donor.

IPC Classes  ?

• C12P 13/22 - TryptophanTyrosinePhenylalanine3,4-Dihydroxyphenylalanine

Abstract

A process for preparation of (R)- aromatic α-hydroxy ketones of formula (I), said process occurring in strain(s) of yeast expressing a recombinant pyruvate decarboxylase, having cysteine residues at positions 221 and 222 of PDC1, an isoenzyme of said pyruvate decarboxylase, substituted with glutamate and alanine respectively such that the said mutation being in the regulatory site of pyruvate decarboxylase, selectively favours carboligation reaction over decarboxylation.

IPC Classes  ?

• C12P 7/26 - Ketones
• C12N 9/88 - Lyases (4.)