105601-20-5

Basic information

• Product Name: RIVASTIGMINE
• Synonyms: 3-[1-(Dimethylamino)ethyl]phenyl Ethyl(methyl)carbamate
• CAS NO: 105601-20-5
• Molecular Formula: C₁₄H₂₂N₂O₂
• Molecular Weight: 250.34
• Mol File: 105601-20-5.mol

Chemical Properties

• Boiling Point: 316.2±34.0 °C(Predicted)
• Appearance: /
• Density: 1.038±0.06 g/cm3(Predicted)
• PKA: 8.62±0.50(Predicted)
• CAS DataBase Reference: RIVASTIGMINE(CAS DataBase Reference)
• NIST Chemistry Reference: RIVASTIGMINE(105601-20-5)
• EPA Substance Registry System: RIVASTIGMINE(105601-20-5)

Safety Data

• Hazardous Substances Data: 105601-20-5(Hazardous Substances Data)

Usage

Uses

(±)-Rivastigmine is a brain selective acetylcholinesterase inhibitor. Nootropic.

Upstream product

• 90870-20-5 4-nitrophenyl ethyl(methyl)carbamate 
• 105601-04-5 (+/-)-3-<1-(Dimethylamino)ethyl>phenol 
• 1392101-39-1 3-(1-bromoethyl)phenyl ethyl(methyl)carbamate 
• 124-40-3 dimethyl amine 
• 624-78-2 N-Ethylmethylamine 
• 530-62-1 1,1'-carbonyldiimidazole 
• 624-60-2 N-methyl-ethylamine hydrochloride 
• 7693-46-1 4-Nitrophenyl chloroformate 
• 50893-53-3 carbonochloridic acid 1-chloro-ethyl ester 
• 1222073-98-4 rac-1-(N-ethyl-N-methylaminocarbonyloxy)-3-(1-hydroxyethyl)benzene 
• 121-71-1 3-Hydroxyacetophenone 
• 855300-09-3 1-(N-ethyl-N-methylaminocarbonyloxy)-3-acetylbenzene 
• 948829-23-0 C₁₇H₁₈N₂O₅ 
• 42252-34-6 N-ethyl-N-methylcarbamoyl chloride 

Downstream Products

• 415973-05-6 (R)-3-(1-(dimethylamino)ethyl) phenylethyl(methyl)carbamate 
• 123441-03-2 rivastigmin 
• 1202748-14-8 R-rivastigmine (-) DPTTA salt 
• 399515-02-7 (S)-N-ethyl-3-[(1-dimethylamino)ethyl]-N-methylphenylcarbamate di-p-toluoyl-D-tartrate 

Relevant articles and documents

A General Catalytic Method for Highly Cost- and Atom-Efficient Nucleophilic Substitutions

A general formamide-catalyzed protocol for the efficient transformation of alcohols into alkyl chlorides, which is promoted by substoichiometric amounts (down to 34 mol %) of inexpensive trichlorotriazine (TCT), is introduced. This is the first example of a TCT-mediated dihydroxychlorination of an OH-containing substrate (e.g., alcohols and carboxylic acids) in which all three chlorine atoms of TCT are transferred to the starting material. The consequently enhanced atom economy facilitates a significantly improved waste balance (E-factors down to 4), cost efficiency, and scalability (>50 g). Furthermore, the current procedure is distinguished by high levels of functional-group compatibility and stereoselectivity, as only weakly acidic cyanuric acid is released as exclusive byproduct. Finally, a one-pot protocol for the preparation of amines, azides, ethers, and sulfides enabled the synthesis of the drug rivastigmine with twofold SN2 inversion, which demonstrates the high practical value of the presented method.

Amorphous and crystalline forms of rivastigmine hydrogentartrate

Rivastigmine hydrogentartrate in amorphous form or in a crystalline form characterized by an X-ray powder diffraction pattern exhibiting peaks at 2Θ values of 5.1, 14.7, 16.5, 17.6, 18.6, 20.4, 21.1° ± 0.2° (Form I), or 2Θ values of 9.5, 11.3, 13.2, 14.1, 15.5, 19.1 20.0° ± 0.2° (Form II), methods for its preparation and pharmaceutical compositions comprising the same.

PROCESS FOR MAKING AMINOALKYLPHENYL CARBAMATES AND INTERMEDIATES THEREFOR

The invention relates to a process for making the compound of general formula (I), or an acid addition salt wherein the dotted line indicates a carbon-carbon bond on the asymmetric carbon, which process comprises the steps of a) the reaction of the compound of formula (II), wherein the dotted line has the same meaning, with bis(p-nitτophenyl)carbonate of the formula (IX) preferably at the temperature between -20 to 50°C and in an inert solvent, followed by b) the reaction of the so formed intermediate of the formula (VII-1) with ethylmethylamine.

Process for the preparation of phenylcarbamates

A process for the preparation of aminoalkyl phenyl carbamate compounds of Formula I, wherein R1 and R2 independently are hydrogen or a C1-6 alkyl; R3 and R4 are the same or different and each is a C1-6 alkyl; or R3 and R4 together with the nitrogen to which they are attached form a cyclic three to eight membered ring, with or without a heteroatom like nitrogen or oxygen; R5 and R6 independently are hydrogen, linear, branched or cyclic C1-6 alkyl; or R5 and R6 together with the nitrogen to which they are attached form a cyclic three to eight membered ring, with or without a heteroatom like nitrogen or oxygen; the carbon centre designated “*” can be racemic or enantiomerically enriched in the (R)— or (S)-configuration; and pharmaceutically acceptable acid addition salts thereof.

AN EFFICIENT METHOD FOR PREPARATION OF (S)-3-[(1-DIMETHYL AMINO)ETHYL]-PHENYL-N-ETHYL-N-METHYL-CARBAMATE

The present invention relates to a method for preparation of substituted phenyl carbamate and pharmaceutically acceptable salts thereof, which are of current pharmaceutical interest. The substituted phenyl carbamate and pharmaceutically acceptable salts thereof are useful to raise cholinergic activity in the central nervous system and useful in treatment of diseases such as Alzheimer's disease, Down's syndrome, Huntingdon's chorea, Friedrich's ataxia etc. (S)-3-[(1-dimethyl amino)ethyl]- phenyl-N-ethyl-N-methyl-carbamate (I) is the active ingredient of the pharmaceutical composition referred in US 5,602,176. This compound is also used to induce selective inhibition of acetylcholinesterase activity in the brain.

NOVEL PROCESSES FOR THE PREPARATION OF AMINOALKYL PHENYLCARBAMATES

The present invention relates to a process for preparing an aminoalkyl phenylcarbamate (4), comprising the steps of converting a hydroxy phenyl ketone (2) to a phenylcarbamate ketone (3), and converting the phenylcarbamate ketone (3) to the desired aminoalkyl phenylcarbamate (4). Optionally the aminoalkyl phenylcarbamate (4) may be resolved into its enantiomers and/or converted into a pharmaceutically acceptable acid addition salt. The invention further relates to aminoalkyl phenylcarbamates (4) and pharmaceutically acceptable salts prepared by the above process, in particular, to rivastigmine (1) and rivastigmine hydrogen tartrate (9). The aminoalkyl phenylcarbamates (4) may be comprised in pharmaceutical compositions. The invention further relates to a method of inhibiting acetylcholine esterase or treating dementia, senile dementia, Alzheimer's disease, Huntington's chorea, tardive dyskinesias, hyperkinesia, a confusion disorder, ataxia, Friedrich's ataxia, Down's syndrome, mania or an acute confusion disorder, using the aminoalkyl phenylcarbamates (4) of the present invention.

A PROCESS FOR THE PREPARATION OF PHENYLCARBAMATES

A process for the preparation of compound of formula (I); wherein R is hydrogen, linear, branched or cyclic lower alkyl, cyclohexyl, allyl, propargyl or benzyl; R is hydrogen, methyl, ethyl or propyl; or R and R together with the nitrogen to which they are attached form a cyclic moiety of three to eight-membered ring, with or without a hetero atom like nitrogen or oxygen; R is hydrogen or lower alkyl; R and R are the same or different and each is a lower alkyl; comprising reacting compound of formula (II); wherein R, R and R are as defined above, with compound of formula (III); wherein Rand R are as defined above, in the presence of a base, and further resolving the compound of formula (I) to obtain (S)-isomer of compound of formula (I), substantially free of R-isomer.

Cyclic phenyl carbamates and their action on acetylcholinesterase

Several six-, seven-, and eight-membered cyclic phenyl carbamates of the miotin type have been synthesised and their in vitro potency as inhibitors of acetylcholinesterase determined. The eight-membered rings were found to be the most potent and are compa