Cyano 4-methoxyphenyl

Other N-methylations of l-[cyano-(4-methoxyphenyl)-methyI]cyclohexanol using formaldehyde, formic acid, and excess water by a modified Eschweiler-Clarke reaction are described (3). 

Reaction of 2-cyano-3-(4-methoxyphenyl)acroyl chloride and 2-amino-pyridine in boiling benzene in the presence of NEt3 for 5 h gave a 2 1 mixture of 3-cyano-4-(4-methoxyphenyl)-3,4-dihydro-2//-pyrido[l, 2-n]pyr-imidin-2-one and 2- [2-cyano-3-(4-methoxyphenyl)acroyl]amino pyridine (01SUL151). 

Likewise 3-amino-2-cyano-4-(3-methoxyphenyl)-A -carboethoxypyrrole is converted into 7-(3-methoxyphenyl)-pyrrolo[3,2- pyrimidin-4-one by, first decarboxylation, and then cyclization in refluxing formic acid <2006BMCL2091>. Replacing the 3-methoxyphenyl group on the pyrrole with a reduced pyrrole (a mimic of a ribofuranose ring) leads to a 4-aminopyrrolo[3,2- pyrimidine when treated with formamidine acetate <2006BMCL2662>. 

Synthesis (Cavalla and White (Wyeth), 1969 1969 Bradley 1980 Kleemann et al. 1999) By condensation of 2-(m-methoxyphenyl)butyronitrile with ethyl 4-iodobutyrate by means of NaNH2 in liquid NH3 to give ethyl 5-cyano-5-(m-methoxyphenyl)heptanoate, which is cyclized by hydrogenation with H2 over Raney Ni in cyclohexane to yield 6-ethyl-6-(m-methoxyphenyl)hexahydro-2H-azepin-2-one this ketone is reduced with LiAIH4 in THF to 3-ethyl-3-(m-methoxyphenyl)hexahydro-IH-azepine, which in turn, is reductively methylated with HCHO, H2 and Pd/C in ethanol to give 1-methyl-3-ethyl-3-(m-methoxyphenyl)-hexahydro-1H-azepine, and finally demethylated by refluxing with 80% HBr to yield a racemic mixture of the final product. 

Cyclization of 3-Amino-1,2,4-triazoles by Reaction with Alkylidene- or Arylidenemalononitrile. [3 + 3] Cycloaddition of 3-amino-l,2,4-triazole (65) onto 4-methoxybenzylidenemalononitrile produced only the 7-amino-6-cyano-5-(4-methoxyphenyl)-l,2,4-triazolo[4,3-a]pyrimidine (66) [88IJC(B) 478)]. The alternative addition that may afford the 5-amino-6-cyano-7-(4-methoxyphenyl)-l,2,4-triazolo[4,3-a]pyrimidine (110) did not take place. Utilization of ethoxymethylene malononitrile in place of arylidenemalononitrile in this reaction gave 66 (R = H) in addition to 7-amino-6-cyano-l,2,4-triazolo[l,5-a]pyrimidine 67 (R = H) (70JPR254) (Scheme 46). 

Cyclization of the piperidone derivative (158) gave rise to diastereomer-ically pure perhydropyrido[2,l-h][l,3]oxazin-6-one (159) (94JA10819). Heating l-(3-methoxy-l-propyl)-2-hydroxy-3-cyano-4-methylpyridin-6(l//)-one in 25% sulfuric acid at 80°C for 2 h gave 8-methyl-6-oxo-2,3,4,6-tetrahydropyrido[2,1 -fo][ 1,3]oxazine-9-carboxamide (89EUP316779). 8-(4-Methoxyphenyl)-2,3,4,6-tetrahydropyrido[2, -b [1,3]oxazine-2,6-dione was obtained by cyclization of 3-[4-(4-methoxyphenyl)-2,6-dioxo-l,2,3,6-... 

Methoxyphenylacetonitrile l-Cyano-l-(3-methoxyphenyl)tridecane 1-Bromododecane N-Methyl-p-(3-methoxyphenyl)ethylamine... 

Structural proofs have been given by comparing some of the preceding condensation products with compounds obtained by reacting elemental sulfur with cinnamylidene compounds. Condensation of 5-p-methoxyphenyl-3-methylthio-l, 2-dithiolium iodide with ethyl cyanoacetate3 5 4 2 folio wed by the ethanolysis of the cyano group gave the same dithiolylidene malonate as the reaction of elemental sulfur on ethyl p-methoxycinnamylidene malonate.15... 

An important application of oxidation of a C-H bond adjacent to a nitrogen atom is the selective oxidation of amides. This reaction proceeds in the presence of ferf-BuOOH as the oxidant and Ru(II) salts. Thus in the example of Eq. (36), the a-tert-butylperoxy amide of the isoquinoline was obtained, which is an important synthetic intermediate for natural products [138]. This product can be conveniently reacted with a nucleophile in the presence of a Lewis add. Direct trapping of the iminium ion complex by a nudeophile was achieved in the presence of trimethylsilyl cyanide, giving a-cyanated amines as shown in Eq. (37) [45]. This ruthenium/peracid oxidation reaction provides an alternative to the Strecker reaction for the synthesis of a-amino acid derivatives since they involve the same a-cyano amine intermediates. In this way N-methyl-N-(p-methoxyphenyl) glycine could be prepared from N,N-dimethyl-p-methoxyaniline in 82% yield. 

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