Pyridine 2-bromo-4-methyl

Isoxazolo[5,4-6]pyridine, 3,5-dimethy 1-,3C NMR, 6, 620 (79S449) Isoxazolo[5,4-6]pyridine, 3-methyl- H NMR, 6, 619 (77JHC435) Isoxazolo[5,4-6]pyridine, 3-methyl-5-phenyl-13C NMR, 6, 620 (79S449) Isoxazolo[2,3-a]pyridinium, 5-bromo-4-hydroxy- H NMR, 6, 619 <7UCS(C)1196>... 

With the catalysis of strong Lewis acids, such as tin(IV) chloride, dipyrromethenes may aiso be alkylated. A very successful porphyrin synthesis involves 5-bromo-S -bromomethyl and 5 -unsubstituted 5-methyl-dipyrromethenes. In the first alkylation step a tetrapyrrolic intermediate is formed which cyclizes to produce the porphyrin in DMSO in the presence of pyridine. This reaction sequence is useful for the synthesis of completely unsymmetrical porphyrins (K.M. Smith, 1975). 

Halothiophenes, which are not activated through the presence of —I—M-substituents, undergo substitution smoothly under more forcing conditions with copper salts in pyridine or quinoline. Hence 3-cyanothiophene and 5-methyl-2-cyanothiophene have been obtained from the corresponding bromo compounds. 2-Bromothiophene reacts readily with aliphatic cuprous mercaptides in quinoline at 200°C to give thioethers in high yields. The use of the copper-catalyzed Williamson synthesis of alkoxythiophenes from iodo- or bromo-thiophenes and alcoholate has been mentioned before. The reaction of 2-bromothiophene with acetanilide in nitrobenzene in... 

Reaction of 2 equiv of 2-aminopyridines with 2-hydropolyfluoroalk-2-anoates 351 in MeCN in the presence of NEts at 90 °C for 50 h afforded a mixture of the isomeric 2-oxo-2H- and 4-oxo-4//-pyrido[l,2-n]pyrimidines 110 and 111. Reaction of 3 equiv of 2-amino-pyridines and 2-hydropoly-fluoroalk-2-enoates 351 in MeCN in the presence K2CO3 could be accelerated by ultrasonic irradiation (125W). 2-Amino-6-methylpyridine yielded only 2-substituted 6-methyl-4//-pyrido[l,2-n]pyrimidin-4-ones 111 (R = 6-Me), whereas 2-amino-5-bromopyridine gave a mixture of 7-bromo-4//-pyrido[l,2-n]pyrimidin-4-one (111, R = 7-Br, R = CF2C1) and 2-(chlor-o,difluoromethyl)-6-bromoimidazo[l, 2-n]pyrimidine-3-carboxylate in 44 and 8% yields, respectively (97JCS(P 1)981). Reactions in the presence of K2CO3 in MeCN at 90°C for 60h afforded only imidazo[l,2-n]pyrimidine-3-carboxylates. 

This pyridine-pyrimidine ring transformation has also been observed on treatment of 2-bromoquinoline with potassium amide in liquid ammonia, 2-methylquinazoline being obtained (67RTC187). Similarly, 8-bromo-l,7-phenanthroline gives 2-methyl-l,3,5-triazaphenanthrene (83JHC447)... 

Amide-induced pyridine-pyrimidine transformation is also reported with 2-bromo-l, 5-naphthyridine. 2-Methyl-4-amino-l, 3,5-triazanaphtha-lene is obtained, together with its 4-amino derivative The presence of the amino group at position 4 is certainly due to a SnH amino-dehydrogenation in preformed 2-methyl-l,3,5-triazanaphthalene (63RTC997, 73RC459, 94MI1). 

By oxidation with chromic acid, this is converted into cyclohexanone-3-carboxylic acid, in which the —CH. OH— group is converted into the —CO— group. This is converted into its ethyl ester and treated with magnesium methyl iodide, and the product, on hydrolysis, yields l-methyl-cyclohexane-l-ol-3-carboxylic acid, which is converted byhydro-bromic acid into 1-bromo-l - methyl - cyclohexane - 3 - carboxylic acid. When this is digested with pyridine, hydrobromic acid is eliminated and yields l-methyl-A -cyclohexane-3-carboxylic acid of the formula—... 

Preparation of 9, 11 -Epoxy-17a-21 -Dihydroxy-16 -Methyl-4-Pregnene-3 0-Dione 21-Acetate To a stirred solution of 100 mg of the 9a-bromo-11(3,17a,2Ttrihydroxy-16 3-methyl-4-pregnene-3,20-dione 21-acetate in 3 ml of tetrahydrofuran and 1 ml of methanol under nitrogen was added 1.02 ml of 0.215 N methanolic sodium methoxide. After 10 minutes at 25°C, 0.2 ml of acetic acid was added and the methanol removed in vacuo. The residue was acetylated with 1.00 ml of pyridine and 0.5 ml of acetic anhydride at 60°C for 70 minutes. The mixture was taken to dryness in vacuo, water added, and the product extracted into chloroform. The residue was crystallized from ether-acetone to give pure 9(3,11 (3-epoxy-17a,21-dihydroxy-16(3-methyl-4-pregnene-3,20-dione 21-acetate. 

A microwave-assisted variant of the Rosenmund von Braun reaction has also been developed (Scheme 73) [83]. DMF at 200 °C proved not very useful for the cyanodehalogenation of methyl (3R)-6-bromo-5-oxo-2,3-dihydro-5ff-[l,3]thiazolo[3,2-a]pyridine-3-carboxylates since only low yields of the corresponding nitrile were obtained, and there were substantial amoimts of unconverted starting material. Extending the reaction time from 10 to 20 min gave more desired reaction product but also significant amoimts of... 

Ethyl substitution at the imidazole 5-position (469) was found to increase potency over the unsubstituted analogue (468), while methyl substitution (470) had a slightly deleterious effect on binding (Table 6.41). Chloro (491), bromo (492), cyano (493) and fluoromethyl (494) substitution at this position were all well tolerated (Table 6.43). Introduction of a chloro-substituted pyridine (475) in place of the more usual / -chlorophenyl group (470) resulted in a slight loss of affinity for the CBi receptor, as did replacement of the p-chloro group of (470) with bromo (471), fluoro (472) and in particular, met-hoxy (473). Trifluoromethyl substitution (474) however, was well tolerated. 

Bromo substituents in the 6- and 6 -positions of 2,2 -bipyridines are particularly reactive, being readily converted to amino,cyano, ° al-koxyl, hydrazino, chloro, and hydrogen groups and by way of the corresponding lithio derivatives to carboxyl, methyl, aldehyde or alkylcarbonyl, and other groupings. 6,6 -Dibromo-2,2 -bi-pyridine also reacts with the disodium derivatives of polyethylene glycols to give crown ethers akin to 100, and 6,6 -bis(chloromethyl)-2,2 -bi-pyridine " and the derived 6,6 -bis(mercaptomethyl)-2,2 -bipyridine... 

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