Nucleophile Substitution an chlorierten Mono‐ und Dicyan‐benzolen

Beck, G.; Degener, E.; Heitzer, Helmut

doi:10.1002/jlac.19687160107

Cited by 13 publications

(5 citation statements)

References 2 publications

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“…The chloro-aminoindazole 10 could be prepared by the reaction of hydrazine with 2,6-dichlorobenzonitrile 9 (Scheme ) . Using 9 had a 2-fold benefit.…”

Section: Resultsmentioning

confidence: 99%

The Discovery and Development of a Safe, Practical Synthesis of ABT-869

Kruger

Rozema

Chu-Kung

et al. 2009

Org. Process Res. Dev.

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The discovery, development and implementation of two chemical routes to ABT-869 is reported. Optimization of the first-generation heterocycle formation and Suzuki coupling is briefly described. Key features of the second-generation synthesis include the development of a safe hydrazine condensation by utilizing an inorganic base to increase the onset temperature of exothermic decomposition. The second-generation Suzuki reaction is discussed in detail, culminating in the use of an oxygen monitor as a PAT to maximize reproducibility on scale.

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“…The chloro-aminoindazole 10 could be prepared by the reaction of hydrazine with 2,6-dichlorobenzonitrile 9 (Scheme ) . Using 9 had a 2-fold benefit.…”

Section: Resultsmentioning

confidence: 99%

The Discovery and Development of a Safe, Practical Synthesis of ABT-869

Kruger

Rozema

Chu-Kung

et al. 2009

Org. Process Res. Dev.

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“…To this solution was added 1 equiv of potassium fluoride and the mixture heated to 90 °C for 2 h. Upon cooling and concentration of the mixture, a solid precipitate formed which was collected and recrystallized from ethanol to give analytically pure product. Synthesis of 2-Aminodichlorotrimesonitriles 18a-m. 16 To a solution of trichlorotrimesonitrile (17) in acetone at room temperature was added a slight molar excess of the desired aniline.…”

Section: Methodsmentioning

confidence: 99%

“…Synthesis of 2-Aminodichlorotrimesonitriles 18a-m.I6 To a solution of trichlorotrimesonitrile (17) in acetone at room temperature was added a slight molar excess of the desired aniline.…”

Section: -Fluoro-456-trichloroisophthalamidementioning

confidence: 99%

“…Trimesonitrile (16) was converted to trichlorotrimesonitrile (17) via catalytic chlorination; reaction of 17 with 1 equiv of the desired substituted aniline formed the aminotrimesonitriles 18. Reaction with 2 equiv of primary lower alkylamines resulted in disubstitution, forming 19, while higher alkyl and aromatic primary amines did not undergo disubstitution under these conditions.…”

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confidence: 99%

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Synthesis and antiinflammatory evaluation of substituted isophthalonitriles and trimesonitriles, benzonitriles, and terephthalonitriles

Heilman¹,

Battershell²,

Pyne³

et al. 1978

J. Med. Chem.

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In an effort to develop nonacidic, nonsteroidal, antiinflammatory agents without gastrointestinal complications, a series of cyanobenzenes was synthesized for antiinflammatory evaluation. Twenty-seven substituted isophthalonitriles, 19 trimesonitriles, 30 benzonitriles, and 16 terephthalonitriles were tested in the rat utilizing the carrageenan-induced pedal edema assay. Based on the performance of phenylbutazone in this assay (43.8% reduction at 100 mg/kg), six compounds, dosed at 50 mg/kg, produced reductions in inflammation comparable to this standard. However, the LD50 value of each compound dosed at this level was in the range of 40--56 mg/kg in the mouse; therefore, further the LD50 value of each compound dosed at this level was in the range of 40--56 mg/kg in the mouse; therefore, further study was not warranted. Fifteen compounds possessed activity in excess of 20% reduction at 200 mg/kg and also possessed LD50 values greater than 300 mg/kg. Of these cyanobenzenes, trimesonitrile (16), 4-chlorobenzonitrile, 2-chloroterephthalonitrile, and 2-fluoroterephthalonitrile with reductions in edema of 32, 30, 46, and 49%, respectively, represent the best candidates for subsequent study.

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“…Treatment of 6-arninoindazole with chlorine in the presence of hydrochloric acid gives an adduct which is reduced by zinc and acid to 4,5,7-trichloro-6-hydroxyindazole [806] . Pentachlorobenzonitrile (357; R = CI) reacts with four equivalents of hydrazine in dimethylformamide at 140 0 to yield 3-amino-4,5,6, 7tetrachloroindazole (359; R = CI) via the corresponding intermediate (358; R = CI); with less hydrazine at room temperature p-substitution occurs predominandy [807] Cyclization of 5-chloro-2-phenylazobenzoic acid with phosphorus pentachloride, phosphorus oxychloride, or thionyl chloride gives 5,7 -dichloro-3-hydroxy-2-phenylindazole, which is converted into 3,5,7-trichloro-2-phenylindazole (356) on further treatment with phosphorus oxychloride [805]. …”

Section: Benzopyrazoles (Indazoles)mentioning

confidence: 99%