67049-00-7

Basic information

• Product Name: 4-Isothiazolecarboxylic acid, 3-phenyl-, ethyl ester
• CAS NO: 67049-00-7
• Molecular Formula: C12H11NO2S
• Molecular Weight: 233.291
• Mol File: 67049-00-7.mol
• Article Data: 7

Chemical Properties

• CAS DataBase Reference: 4-Isothiazolecarboxylic acid, 3-phenyl-, ethyl ester(CAS DataBase Reference)
• NIST Chemistry Reference: 4-Isothiazolecarboxylic acid, 3-phenyl-, ethyl ester(67049-00-7)
• EPA Substance Registry System: 4-Isothiazolecarboxylic acid, 3-phenyl-, ethyl ester(67049-00-7)

Safety Data

• Hazardous Substances Data: 67049-00-7(Hazardous Substances Data)

Upstream product

• 5852-49-3 5-phenyl-1,3,4-oxathiazol-2-one 
• 83553-48-4 ethyl 2-iodothiazole-5-carboxylate 
• 71-43-2 benzene 
• 172678-67-0 ethyl 2-phenyl-1,3-thiazole-5-carboxylate 
• 53256-19-2 ethyl (Z)-3-amino-3-phenylacrylate 
• 68-12-2 N,N-dimethyl-formamide 
• 95-50-1 1,2-dichloro-benzene 
• 27545-54-6 3-phenyl-isothiazole-4,5-dicarboxylic acid 
• 55-21-0 benzamide 
• 18160-82-2 3-phenyl-1,2-thiazole-4-carboxylic acid 
• 124413-63-4 ethyl 3-amino-3-phenyl-2-propenoate 
• 124413-13-4 ethyl 3-amino-3-phenyl-2-thioformylacrylate 
• 623-47-2 propynoic acid ethyl ester 
• 33831-72-0 ethyl 3-amino-3-phenylprop-2-enoate 

Downstream Products

• 138128-85-5 4-(chloromethyl)-3-phenylisothiazole mesylate 
• 110703-81-6 [4-Oxo-3-(3-phenyl-isothiazol-4-ylmethyl)-3,4-dihydro-phthalazin-1-yl]-acetic acid ethyl ester 
• 112065-65-3 [4-Oxo-3-(3-phenyl-isothiazol-4-ylmethyl)-3,4-dihydro-phthalazin-1-yl]-acetic acid 

Relevant articles and documents

Lead Optimization Generates CYP11B1 Inhibitors of Pyridylmethyl Isoxazole Type with Improved Pharmacological Profile for the Treatment of Cushing's Disease

Cushing's disease, characterized by elevated plasma cortisol levels, can be controlled by inhibition of 11β-hydroxylase (CYP11B1). The previously identified selective and potent CYP11B1 inhibitor 5-((5-methylpyridin-3-yl)methyl)-2-phenylpyridine Ref 7 (IC50= 2 nM) exhibited promutagenic potential as well as very low oral bioavailability in rats (F = 2%) and was therefore modified to overcome these drawbacks. Successful lead optimization resulted in similarly potent and selective 5-((5-methoxypyridin-3-yl)methyl)-3-phenylisoxazole 25 (IC50 = 2 nM, 14-fold selectivity over CYP11B2), exhibiting a superior pharmacological profile with no mutagenic potential. Furthermore, compound 25 inhibited rat CYP11B1 (IC50 = 2 μM) and showed a high oral bioavailability (F = 50%) and sufficient plasma concentrations in rats, providing an excellent starting point for a proof-of-principle study.

Microwave-induced generation and reactions of nitrile sulfides: An improved method for the synthesis of isothiazoles and 1,2,4-thiadiazoles

The 1,3-dipolar cycloaddition reactions of nitrile sulfides, generated by microwave-assisted decarboxylation of 1,3,4-oxathiazol-2-ones, have been investigated. By this approach ethyl 1,2,4-thiadiazole-5-carboxylates 3 were prepared in good yield by cycloaddition of the nitrile sulfides to ethyl cyanoformate. Similarly, reaction of benzonitrile sulfide with dimethyl acetylenedicarboxylate (DMAD) afforded dimethyl 3-phenylisothiazole-4,5- dicarboxylate (5). In contrast, o-hydroxybenzonitrile sulfide, generated from the corresponding oxathiazolone 2d, reacted with DMAD to give methyl 4-oxo-4H-[1]benzopyrano[4,3-c]isothiazole-3-carboxylate (8) in high yield. A ca. 1:1 mixture of ethyl 3-phenylisothiazole-4- and 5-carboxylates (6,7) was formed from benzonitrile sulfide and ethyl propiolate. The corresponding reaction with diethyl fumarate gave diethyl trans-4,5-dihydro-3-phenylisothiazole-4,5- dicarboylate (10). 3-Arylisothiazoles, unsubstituted at both the 4- and 5-positions, were prepared from the reaction of 5-aryl-1,3,4-oxathiazolones with norbornadiene by a pathway involving cycloaddition of the nitrile sulfide to the norbornadiene, followed by retro-Diels-Alder extrusion of cyclopentadiene from the resulting isothiazoline cycloadduct 12. In summary, the use of microwave irradiation, rather than conventional heating methods, allows nitrile sulfide generation and reactions to be carried out in shorter times, with easier work-up and, in some cases, in higher yields.

Synthesis of 2-llkoxycarbonyl enamino thioaldehydes and selenaldehydes (as Pentacarbonyltungsten(0) Complexes). Improved synthesis of simple and 2-cyano enamino thioaldehydes and some chemical reactions of these compounds

A series of stable 2-alkoxycarbonyl enamino thioaldehydes (2a-g) were synthesized by solvolysis of the Vilsmeier salts (1) with aqueous or methanolic sodium hydrogen sulphide. Three 2-alkoxycarbonyl enamino selenaldehydes were obtained as the pentacarbonyltungsten(o) complexes (7a-c). The 2-cyano and simple enamino thioaldehydes (3a-m) and (6a-j) (including some new homologues obtained by an improved synthetic method) are described. Some reactions of 2-cyano and 2-alkoxycarbonyl enamino thioaldehydes were examined e.g. oxidation with MCPBA to give the isothiazoles (8). The symmetrically tetrasubstituted pyridines (9) were produced by bimolecular cyclisation under acidic conditions: hydrolysis in acidic 95% aq. EtOH gave the enamino aldehydes (11) and aroylacetonitriles (12) together with (9). The imines (13) were formed in good yield on reaction with primary amines.