51-57-0

Usage

Uses

Used in Pharmaceutical Industry:
(+)METHAMPHETAMINE HYDROCHLORIDE is used as a medicinal compound for [application reason] due to its central nervous system activity and similarity to dextroamphetamine. It is used in the treatment of attention deficit hyperactivity disorder (ADHD) and as a component in certain nasal decongestants.
Used in Research and Forensic Applications:
(+)METHAMPHETAMINE HYDROCHLORIDE is used as an analytical reference material for [application reason] in research and forensic applications. Its role in these fields is to provide a reference for the identification and analysis of the compound, which is crucial in understanding its effects and potential for abuse.
Used in Drug Enforcement and Policy:
(+)METHAMPHETAMINE HYDROCHLORIDE is used as a regulated substance for [application reason] in drug enforcement and policy. Its classification as a Schedule II compound in the United States indicates its high potential for abuse and the need for strict control over its production, distribution, and use.

Originator

Desoxyn ,Abbott Laboratories

Manufacturing Process

2 Methods of prepearing of methamphetamine: 1. (-)-Ephedrin was reduced by hydrogenesation with hydrogen in the presence of Pt-C catalyst to give the (+)-N-α-dimethylphenethylamine (methamphetamine), melting point 172°-174°C.2. Methamphetamine was obtained by the methylation of phenylisopropylamine. To give methamphetamine hydrochloride the base methamphetamine was treated by eqimolar quantity of hydrochloric acid.

Therapeutic Function

Sympathomimetic, Central stimulant

Biochem/physiol Actions

Sympathomimetic with more potent central effects than amphetamine. It is transported into terminals via the monoamine transporters and induces release of dopamine, norepinephrine, epinephrine, and serotonin. Dopamine release is important for the addictive properties of methamphetamine while norepinephrine and epinephrine release are important for the cardiovascular effects. Serotonin neurotoxin.

Safety Profile

Poison by ingestion, subcutaneous, intravenous, and intraperitoneal routes. An experimental teratogen. Experimental reproductive effects. Questionable carcinogen with experimental neoplastigenic data. When heated to decomposition it emits toxic fumes of NOx and HCl. See also BENZEDRINE and various amphetamines.

InChI:InChI=1/C10H15N.ClH/c1-9(11-2)8-10-6-4-3-5-7-10;/h3-7,9,11H,8H2,1-2H3;1H/t9-;/m0./s1

Upstream product

• 537-46-2 Methamphetamin 
• 100-44-7 benzyl chloride 
• 299-42-3 ephedrine 
• 345-78-8 Novafed 
• 50-98-6 ephedrine hydrochloride 
• 1334921-74-2 C₁₅H₂₃NO₂ 
• 152614-95-4 BOC-pseudoephedrine 

Downstream Products

• 89578-44-9 (S)-(+)-N-Propionyl-N-methylamphetamine 
• 5411-22-3 benzfetamine hydrochloride 
• 6192-97-8 (S)-1-cyclohexyl-N-methylpropan-2-amine 
• 1587700-82-0 C₁₈H₂₉NO₂ 
• 156-08-1 benzphetamine 
• 77001-77-5 C₁₂H₁₄F₃NO 
• 1292765-48-0 (S)-6-mercapto-N-(4-(2-(methylamino)propyl)phenyl)hexanamide 
• 1292765-47-9 (S)-N-(4-(2-(2,2,2-trifluoro-N-methylacetamido)propyl)phenyl)-6-(tritylthio)hexanamide 
• 131654-31-4 (S)-N-(1-(4-aminophenyl)propan-2-yl)-2,2,2-trifluoro-N-methylacetamide 
• 131654-30-3 (S)-2,2,2-trifluoro-N-methyl-N-(1-(4-nitrophenyl)propan-2-yl)acetamide 
• 95688-67-8 [Hydroxy(4-phenylbutyl)phosphinyl]acetic acid, ethyl ester 
• 14482-57-6 Phenylpropionyl-L-pervitin 

Relevant academic research and scientific papers

A short enantioselective synthesis of ephedrine, amphetamine and their analogues via two stereocentered Co(III)-catalyzed hydrolytic kinetic resolution of racemic syn-benzyloxy epoxide

An efficient route for the synthesis of 6 drugs belonging to phenethylamine and amphetamine classes in excellent overall yields and high optical purity has been described. The strategy involves introduction of stereogenic centers by means of two-stereocentered Co(III)-catalyzed hydrolytic kinetic resolution (HKR) of racemic syn-benzyloxy epoxide followed by Pd-catalyzed regioselective cationic hydrogenation of amino alcohols as the key reactions.

An efficient, scalable process for benzphetamine hydrochloride

Commercial manufacturing of benzphetamine hydrochloride along with its impurity profiling is disclosed. Deoxygenation of pseudoephedrine is reported with ～100% retention by shielding the amine group as its tert-butyl carbamate, which is very straightforward to eliminate at the end. Four unknown process-related impurities are isolated from the samples of final API and characterized on the basis of their NMR and mass spectral analysis. Structures of the isolated impurities are confirmed by independent syntheses and coinjecting with the isolated one.

Significant determinants of isotope composition during HI/Pred synthesis of methamphetamine

Methamphetamine HCl was synthesized using three variations of the hydriodic acid/red phosphorus (HI/Pred) synthetic route. A Plackett-Burman experimental design was used to determine how reaction parameters affected the isotopic composition of the product. Isotope ratio mass spectrometry results showed only the source of precursor 13C was significant in determining product δ13C; the manufacturer, reaction temperature, time, scale, and source of HI were not significant. The precursor was also the main determinant of product δ2H, with smaller contributions from the HI source for one method. From precursor to product, large δ2H depletion occurred for most samples. Deuterium nuclear magnetic resonance spectroscopy (2H NMR) was used to investigate the specific site of this. Significant fraction of deuterium was observed only at the benzylic position, the site of hydrogen addition during synthesis. Methamphetamine synthesized from ephedrine was shown to be depleted in this position.

Evaluation of characteristic deuterium distributions of ephedrines and methamphetamines by NMR spectroscopy for drug profiling

We have established a method for quantitative analysis of the deuterium contents (D/H) at the phenyl, methine, benzyl, N-methyl and methyl groups of l-ephedrine/HCl, d-pseudoephedrine/HCl and methamphetamine/HCl by 2H NMR spectroscopy. Comparison of the 5 position-specific D/H values of l-ephedrine/HCl and d-pseudoephedrine/HCl prepared by three methods (chemical synthesis, semichemical synthesis, and biosynthesis) showed that chemically synthesized ephedrines and semi-synthetic ephedrines have highly specific distributions of deuterium at the methine position and at the benzyl position, compared with the other positions. The classification of several methamphetamine samples seized in Japan in terms of the D/H values at these two positions clearly showed that the methamphetamine samples had been synthesized from ephedrines extracted from Ephedra plants or semisynthetic ephedrines but not from synthetic ephedrine. This isotope ratio analysis method should be useful to trace the origins of seized methamphetamine in Southeast Asia.

PROCESS FOR PREPARING BENZYLATED AMINES

This present invention relates to a process for preparing benzylated amines by the reaction of an amine selected from methamphetamine and propylhexedrine with benzyl halide. Numerous improvements are obtained by employing the amine in molar excess with respect to benzyl halide, preferably in a molar ratio of 2 to 1. The excess amine is employed to selectively neutralize by-product acid as the amine salt. The amine salt is then separated from the reaction mixture and basified to reclaim starting amine for recycle to the process.