101403-24-1

Basic information

• Product Name: (S)-1,2,3,4-tetrahydro-5-methoxy-N-propyl-2-Naphthalenamine(Rotigotine)
• Synonyms: (S)-1,2,3,4-tetrahydro-5-methoxy-N-propyl-2-Naphthalenamine(Rotigotine);(S)-1,2,3,4-Tetrahydro-5-methoxy-N-propyl-2-naphthalenamine;Rotigotine InterMediate;(S)-5-Methoxy-N-propyl-1,2,3,4-tetrahydronaphthalen-2-aMine;2-NaphthalenaMine, 1,2,3,4-tetrahydro-5-Methoxy-N-propyl-, (S)-
• CAS NO: 101403-24-1
• Molecular Formula: C₁₄H₂₁NO
• Molecular Weight: 219.32
• Product Categories: APIs Intermediate
• Mol File: 101403-24-1.mol

Chemical Properties

• Boiling Point: 346.117 °C at 760 mmHg
• Flash Point: 143.285 °C
• Appearance: /
• Density: 1.014 g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.533
• PKA: 10.26±0.20(Predicted)
• CAS DataBase Reference: (S)-1,2,3,4-tetrahydro-5-methoxy-N-propyl-2-Naphthalenamine(Rotigotine)(CAS DataBase Reference)
• NIST Chemistry Reference: (S)-1,2,3,4-tetrahydro-5-methoxy-N-propyl-2-Naphthalenamine(Rotigotine)(101403-24-1)
• EPA Substance Registry System: (S)-1,2,3,4-tetrahydro-5-methoxy-N-propyl-2-Naphthalenamine(Rotigotine)(101403-24-1)

Safety Data

• Hazardous Substances Data: 101403-24-1(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
(S)-1,2,3,4-tetrahydro-5-methoxy-N-propyl-2-Naphthalenamine (Rotigotine) is used as a transdermal patch for the treatment of Parkinson's disease and restless legs syndrome. It modulates the dopamine receptors in the brain, providing relief from motor control issues and mood disturbances associated with these conditions.
Additionally, it is being investigated for its potential in treating other conditions such as depression and attention deficit hyperactivity disorder (ADHD), where its dopamine agonist properties may offer therapeutic benefits.
Rotigotine is available by prescription and should be used under the guidance of a healthcare professional. Common side effects include dizziness, nausea, and skin irritation at the application site.

InChI:InChI=1/C14H21NO/c1-3-9-15-12-7-8-13-11(10-12)5-4-6-14(13)16-2/h4-6,12,15H,3,7-10H2,1-2H3/t12-/m0/s1

Upstream product

• 107-10-8 propylamine 
• 32940-15-1 5-methoxy-2-tetralone 
• 105086-92-8 (S)-5-methoxy-2-amino-1,2,3,4-tetrahydronaphthalene 
• 4018-91-1 2-Amino-5-methoxy-1,2,3,4-tetrahydronaphthalene 
• 1374308-75-4 C₁₄H₁₉NO 
• 244239-68-7 (R)-N-(5-methoxy-1,2,3,4-tetrahydronaphthalen-2-yl)propionamide 
• 1222074-03-4 (S)-(-)-2-(N-propylamino)-5-methoxytetraline (+)-N-(3,5-dinitrobenzoyl)-α-phenylglycine salt 
• 136247-07-9 2-(N-benzylamino)-5-methoxytetralin 
• 58349-23-8 (S)-(-)-2-(N-benzylamino)-5-methoxytetralin 
• 58349-15-8 (S)-5-methoxy-1,2,3,4-tetrahydronaphthalen-2-amine hydrochloride 
• 244239-67-6 (S)-N-(5-methoxy-1,2,3,4-tetrahydronaphthalen-2-yl)propionamide 

Downstream Products

• 93601-86-6 (S)-(-)-(5-methoxy-1,2,3,4-tetrahydronaphthalen-2-yl)propylamine hydrochloride 
• 1148154-91-9 (2S)-5-methoxy-N-propyl-N-(2'-(thien-2-yl)ethyl)tetralin-2-amine 
• 78598-91-1 2-(N-propylamino)-5-methoxytetraline 
• 1563175-00-7 (S)-5-methoxy-N-(2-(4-(3′-methoxybiphenyl-4-yl)piperazin-1-yl)ethyl)-N-propyl-1,2,3,4-tetrahydronaphthalen-2-amine 
• 125572-93-2 rotigotine hydrochloride 
• 99755-59-6 rotigotine 
• 165950-84-5 (S)-1,2,3,4-tetrahydro-5-hydroxy-N-propyl-naphthalen-2-ammonium hydrobromide 
• 136316-06-8 (S)-(-)-2--5-methoxytetralin 
• 129388-80-3 (S)-(-)-2--5-hydroxytetralin 
• 136247-11-5 N-((S)-5-Methoxy-1,2,3,4-tetrahydro-naphthalen-2-yl)-2-(4-nitro-phenyl)-N-propyl-acetamide 
• 101470-23-9 Desthienyl-Rotigotine 

Relevant articles and documents

New catalytic route for the synthesis of an optically active tetralone-derived amine for rotigotine

Rotigotine is a launched drug for the treatment of Parkinson's disease and restless legs syndrome. The key steps of an alternative route for the synthesis of rotigotine have been demonstrated. Formation of a prochiral enamide, asymmetric hydrogenation of the enamide with high enantioselectivity, and reduction of the resulting amide to an amine have been proved to work successfully. The best conditions screened to date for the asymmetric hydrogenation of enamide 9 to amide 10 were with [(RuCl((R)-T-BINAP))2(μ-Cl)3][NH2Me2] at 25 bar H2 and 30 °C (500:1 S/C ratio, 99% conversion, 91% ee S). Reduction of amide 10 to amine 5 was best achieved with Red-Al giving 95% conversion.

Synthesis and pharmacology of the enantiomers of the potential atypical antipsychotic agents 5-OMe-BPAT and 5-OMe-(2,6-di-OMe)-BPAT

The optically pure enantiomers of the potential atypical antipsychotic agents 5-methoxy-2-[N-(2-benzamidoethyl)-N-n-propylamino]tetralin (5-OMe-BPAT, 5) and 5-methoxy-2-{N-[2-(2,6-dimethoxy)benzamidoethyl]-N-n-propylamino}tetralin [5-OMe-(2,6-di-OMe)-BPAT

Synthesis of Pharmaceutically Relevant 2-Aminotetralin and 3-Aminochroman Derivatives via Enzymatic Reductive Amination

2-Aminotetralin and 3-aminochroman derivatives are key structural motifs present in a wide range of pharmaceutically important molecules. Herein, we report an effective biocatalytic approach towards these molecules through the enantioselective reductive coupling of 2-tetralones and 3-chromanones with a diverse range of primary amine partners. Metagenomic imine reductases (IREDs) were employed as the biocatalysts, obtaining high yields and enantiocomplementary selectivity for >15 examples at preparative scale, including the precursors to Ebalzotan, Robalzotan, Alnespirone and 5-OH-DPAT. We also present a convergent chemo-enzymatic total synthesis of the Parkinson's disease therapy Rotigotine in 63 % overall yield and 92 % ee.

Preparation method of rotigotine

The invention relates to the technical field of medicine preparation, and discloses a preparation method of rotigotine, which comprises the following steps: by taking 5-methoxy-2-tetralone as an initial raw material, reacting with R-alpha-methylbenzylamine, performing debenzylation reduction and S-mandelic acid chiral resolution, then reacting with a propionyl chloride reagent to generate an amide compound, and then reducing by a sodium borohydride reagent to obtain the rotigotine; and finally, reacting with 2-(thiophene-2-yl) 2-nitric acid benzene sulfonic acid ethyl ester to obtain the rotigotine. The preparation process route is as follows: the rotigotine is mild in preparation condition, simple and convenient to operate, relatively high in yield of key intermediates, high in optical purity and easy for industrial large-scale production, and has a very good application prospect.

Preparation method for rotigotine

The invention discloses a preparation method for rotigotine. The preparation method includes the following steps: S1. performing an amination reduction reaction on a 5-methoxy-2-tetralone solution, tert-butanesulfinamide, a catalyst, and sodium borohydride to obtain a substance A; S2. performing an alkylation reaction on a solution of the substance A, bromopropane, and a basic catalyst to obtain asubstance B; S3. reacting the substance B with a hydrochloric acid methanol solution to obtain a substance C; S4. performing a reaction on the substance C, 2-(2-bromoethyl)thiophene, potassium carbonate, and N,N-dimethylformamide to obtain a substance D; and S5. reacting acetic acid with hydrogen bromide to obtain the rotigotine. The preparation method is simple in operation, is high in yield, ismild in reaction condition, is green and environmentally friendly, is high in purity of the prepared rotigotine, and is suitable for large-scale industrial production.

Enantioselective Synthesis of β-Aminotetralins via Chiral Phosphoric Acid-catalyzed Reductive Amination of β-Tetralones

A new protocol for the synthesis of chiral β-aminotetralins has been developed via chiral phosphoric acid-catalyzed asymmetric reductive amination of β-tetralones using a Hantzsch ester as an organic hydride donor. Various chiral β-aminotetralins were obtained in good yields with good to high enantioselectivities. Furthermore, the utility of our new protocol was successfully demonstrated in the enantioselective synthesis of rotigotine. (Figure presented.).

PROCESSES FOR THE PREPARATION OF ROTIGOTINE AND INTERMEDIATES THEREOF

The present invention provides processes for the preparation of a compound of Formula 2 or a salt thereof, wherein R1 is selected from the group consisting of H, C1-C3 alkyl, and C(0)R3; R3 is selected from the group consisting of C1-C6 alkyl, C6-C10aryl and C7-C20 arylalkyl; the carbon atom marked with "*" is racemic, enantiomerically enriched in the (R)-configuration, or enantiomerically enriched in the (S)-configuration. Also provided are intermediate compounds of the processes.

luo Ti gastrodia tuber of a kind of preparation method

The invention discloses a preparation method of rotigotine, and belongs to the technical field of medicine synthesis. According to the method, 5-methoxy-2-tetralone is used as a raw material for amination, asymmetric reduction, halogenation and methoxyl group removal four step reaction for synthesis of chiral rotigotine {(-)-(S)-2-(N-propyl-N-(2-(2-thiophene) ethyl] amino]-5-hydroxy-1, 2, 3, 4-tetralin}. According to the method, a simplex stereoscopic structural compound is synthesized by stereo selective chemical reaction, in the asymmetric reduction process, hantzsch ester 1, 4-dihydropyridine (HEH) is used as a reducing agent, and chiral phosphoric acid is used as a catalyst to synthesize an important intermediate (S)-2-(N-n-propyl) amido-5-methoxy tetralin (II) with a simplex stereoscopic structure, the use of a chiral reagent for splitting to obtain the simplex stereoscopic structural compound is avoided, the synthesis procedure is shortened, the yield is improveds, and the method is favorable for industrialized production.

COMPOSITIONS AND METHODS FOR TREATMENT OF NEUROLOGIC DISEASES

Provided are compounds, pharmaceutical acceptable salts, polymorphs, solvates, enantiomers, stereoisomers and hydrates thereof. The pharmaceutical compositions comprising the compounds may be formulated for oral, buccal, rectal, topical, transdermal, transmucosal, intravenous, parenteral administration, syrup or injection, and may be used for the treatment of neurologic diseases, such as depression, Alzheimer's disease, multiple sclerosis, Batten disease, Parkinson's disease and restless legs syndrome.

PROCESS FOR THE PREPARATION OF OPTICALLY ACTIVE (S)-(-)-2-(N-PROPYLAMINO)-5-METHOXYTETRALINE AND (S)-(-)-2-(N-PROPYLAMINO)-5-HYDROXYTETRALINE COMPOUNDS

The present invention describes a novel process for the preparation of optically active (S)-(?)-2-(N-propylamino)-5-methoxytetraline and (S)-(?)-2-(N-propylamino)-5-hydroxytetraline compounds based on the optical resolution of mixtures of the enantiomers of 2-(N-propylamino)-5-methoxytetraline and 2-(N-propylamino)-5-hydroxytetraline respectively. This process comprises (a) reacting a mixture of the enantiomers of said compounds with an optically active organic acid to form diastereoisomeric salts and separating the salts by crystallization. Said compounds are useful in the preparation of (6S)-(?)-5,6,7,8-tetrahydro-6-[propyl-(2-thienyl)ethyl]amino-1-naphthol (Rotigotine). Rotigotine is a dopamine agonist and is indicated for the treatment of Parkinson's disease.