243119-20-2

Basic information

• Product Name: Isoxazole, 3-methyl-5-(1-methyl-2-pyrrolidinyl)- (9CI)
• Synonyms: Isoxazole, 3-methyl-5-(1-methyl-2-pyrrolidinyl)- (9CI)
• CAS NO: 243119-20-2
• Molecular Formula: C9H14N2O
• Molecular Weight: 166.22026
• Product Categories: OXAZOLE
• Mol File: 243119-20-2.mol

Chemical Properties

• Appearance: /
• CAS DataBase Reference: Isoxazole, 3-methyl-5-(1-methyl-2-pyrrolidinyl)- (9CI)(CAS DataBase Reference)
• NIST Chemistry Reference: Isoxazole, 3-methyl-5-(1-methyl-2-pyrrolidinyl)- (9CI)(243119-20-2)
• EPA Substance Registry System: Isoxazole, 3-methyl-5-(1-methyl-2-pyrrolidinyl)- (9CI)(243119-20-2)

Safety Data

• Hazardous Substances Data: 243119-20-2(Hazardous Substances Data)

Upstream product

• 50-00-0 formaldehyd 
• 147402-52-6 A 79814 
• 163849-08-9 5(S)-(3-methyl-5-isoxazolyl)-2-pyrrolidinone 
• 173521-73-8 (S)-2-(3-aminobut-2-enoyl)-N-methylpyrrolidine 
• 163849-06-7 3-methyl-5-(1-methyl-2-pyrrolidinyl)-5-hydroxy-4,5-dihydro-isoxazole 
• 770712-14-6 (S)-2-(3-Methyl-isoxazol-5-yl)-pyrrolidine-1-carboxylic acid ethyl ester 
• 53310-79-5 ethyl (2S)-2-(hyroxymethyl)pyrrolidine-1-carboxylate 
• 770712-13-5 ethyl (2S)-2-[(1E)-3-oxobut-1-enyl]pyrrolidine-1-carboxylate 
• 15761-39-4 1-(tert-butoxycarbonyl)-L-proline 
• 69610-40-8 N-(tert-butoxycarbonyl)-L-prolinol 
• 69610-41-9 Boc-L-Pro-H 
• 130418-90-5 (S)-tert-butyl 2-ethynylpyrrolidine-1-carboxylate 
• 130419-38-4 (S)-2-(2,2-dibromoethenyl)-1-pyrrolidinecarboxylic acid 1,1-dimethylethyl ester 
• 147402-51-5 (S)-3-methyl-5-<1-(tert-butoxycarbonyl)-pyrrolidinyl>isoxazole 

Relevant articles and documents

Domino primary alcohol oxidation-wittig reaction: Total synthesis of ABT-418 and (E)-4-oxonon-2-enoic acid

Domino oxidation of primary alcohols to α,β-unsaturated compounds using the combination of PCC-NaOAc and stabilized Wittig reagent and its application towards total synthesis of ABT-418 and 4-oxonon-2-enoic acid is described.

Pyrrolidines bearing a quaternary α-stereogenic center. Part 1: Synthesis of analogs of ABT-418, a powerful nicotinic agonist

We describe herein the synthesis of various analogs of ABT-418, in which the stereogenic center is at the same time both quaternary and functional. The key step is the obtention of the aminoaldehyde 1a by means of ring contraction of the parent heterocycl

An efficient, scaleable procedure for the conversion of esters to isoxazoles

A concise, regiocontrolled route to isoxazoles, based on the condensation of an ester with a metallated imine, has been developed. The intermediate vinylogous amides react smoothly with hydroxylamine to provide, after dehydration, substituted isoxazoles. The method has been used for the multi-kilo scale preparation of ABT-418, a novel cholinergic channel activator.

Synthesis and 11C-labelling of two selective high affinity nicotinic cholinergic agonists for evaluation as radioligands for PET studies

ABT-418 ((S)-3-methyl-5-[1-methyl-2-pyrrolidinyl]isoxazole) and N-methylcytisine (N-methyl- 1,2,3,4,5,6-hexahydro-1,5-methano-8H-pyrido-[1,2-a][1,5]diazocin-8-one) are two high affinity nicotinic cholinergic agonists. ABT-418 was synthesized in 7 steps from commercially available (S)-Boc- proline in 35% overall yield. Methylation of commercial cytisine cleanly gave N-methyl-cytisine. ABT-418 and N-methylcytisine were labelled using [11C]methyl iodide by methylation of the corresponding nor-precursors for their in vivo evaluation as positron emission tomography (PET) probes of the nicotinic cholinergic receptors in baboon brain. As for [11C]nicotine, specific binding in vivo could not be demonstrated for ABT-418. Therefore, further experiments are needed to determine the full PET pharmacological profile and the subsequent potential clinical applications of ABT-418 as a tracer for PET experiments. For labelled N-methyl-cytisine, radioactivity in the cerebral cortex and in tile blood were similar. Thus, 11C-labelled N-methylcytisine does not appear to be a suitable ligand for mapping brain nAChR.

Intermediates for the preparation of enantiomerically-pure-3-methyl-5-(1-C1-C3-alkyl)-2-pyrrolidinyl)isoxazole

Novel compounds useful in the preparation of enantiomerically-pure 3-methyl-5-(1-(C1 -C3 -alkyl)-2-pyrrolidinyl)isoxazole in high yield, namely 5(S)-(3-methyl-5-isoxazolyl)-2-pyrrolidinone, 3-methyl-5-(1-methyl-2-pyrrolidinyl)-5-hydroxy-4,5-dihydro-isoxazole, and 1-(1-methyl-2(S)-pyrrolidinyl)-1,3-butanedione-3-oxime.

Method of preparing enantiomerically-pure 3-methyl-5-(1-alkyl-2(s)-pyrrolidinyl)isoxazoles

A novel process for preparing enantiomerically-pure 3-methyl-5-(1-(C1 -C3 -alkyl)-2-pyrrolidinyl)isoxazole in high yield, wherein a protected 2-oxo-pyrrolidine starting material is reacted with a suitable organic anion and a resulting beta-keto oxime intermediate is cyclized and dehydrated.

Method of preparing enantiomerically-pure 3-methyl-5-(1-alkyl-2(S)-pyrrolidinyl) isoxazoles

A novel process for preparing enantiomerically-pure 3-methyl-5-(1-(C1 -C3 -alkyl)-2-pyrrolidinyl)isoxazole in high yield, wherein a protected pyrrolidine or 2-oxo-pyrrolidine starting material is reacted with a suitable organic anion and a resulting beta-keto oxime intermediate is cyclized and dehydrated, as well as intermediates useful in the preparation thereof.

A short, efficient chiral synthesis of a novel cholinergic channel activator, ABT-418 [(S)-3-methyl-5-(1-methyl-2-pyrrolidinyl)isoxazole], from (S)-pyroglutamic acid

ABT-418 [(S)-3-methyl-5-(1-methyl-2-pyrrolidinyl)isoxazole] (1) is a cholinergic channel activator with potent cognitive and anxiolytic activities in animal models. A three-pot synthesis of enantiomerically pure ABT-418 starting from commercially available (S)-pyroglutamic acid is described. The overall yield of the synthesis is 43%.