N- 4-cyano-3-

Chemical Name Propanamide, N-(4-cyano-3-(trifluoromethyl)phenyl)-3-((4-fluorophenyl)sulfonyl)-2-hydroxy-2-methyl- (racemic mixture)... 

N-(4-cyano-3-trifluoromethylphenyl)-3-(4-fluoropher>ylsulfonyl)-2-hydro)ty-2-methylpropionamide (IV)... 

Numerous examples of N—S bond formation using oxidative conditions have been described in the literature. A convenient synthesis of isothiazoles involves the direct oxidation of -y-iminothiols and numerous variations have been studied (see Chapter 4.17), The oxidation of the amidine (248) to give the 3-aminoisothiazole (249) illustrates the reaction scheme (65AHC(4)107, 72AHC(14)1), which has been extended to the synthetically useful 5-amino-4-cyano-3-methylisothiazole (251) obtained by oxidation of (250) with hydrogen peroxide (75JHC883). 

Reaction of 4-cyano-3-imino-2,3,5,6,7,8-hexahydro-l//-pyrido[l,2-c]pyr-imidin-l-one 169 with 2-chloroethyl isocyanate at ambient temperature and under reflux gave N-acylated 170 and tetracyclic derivative 171, respectively (95MI1). Similar reaction of 3-amino-4-cyano-2,4a5,6,7,8-hexahydro-l// pyrido[l,2-c]pyrimidin-1-ones 172 afforded tricyclic compounds 173. 

N-(4-hydroxycyclohexyl)-3-mercapto-3-cyano-4-arylazetidine-2-ones were synthesized from N-(4-hydroxycyclohexyl)aryldiimine by reaction with ethyl a-mercapto-a-cyanoacetate on basic alumina under microwaves. The reaction time was reduced from hours to minutes in comparison to conventional heating and, moreover, the yield was improved [121]. 

G. Pilcher, W. E. Acree Jr., J. R. Powell. Enthalpies of Combustion of the Pyridine N-oxide Derivatives 4-Methyl-, 3-Cyano-, 4-Cyano-, 3-Hydroxy-, 2-Carboxy-, 4-Carboxy-, and 3-Methyl-4-Nitro, and of the Pyridine Derivatives 2-Carboxy- and 4-Carboxy-. The Dissociation Enthalpies of the N-O Bonds. J. Chem. Thermodynamics 1998, 30, 869-878. (b) M. D. M. C. Ribeiro da Silva, personal communication. 

CijH NjOj 90357-51-0) see Bicalutarnide 4 -cyano-3 -trifluoromethylmethacrylanilidc (Cl2H,7F7N20 90357-53-2) sec Bicalutarnide AL[4-cyano-2-(trifluoromethyl)phenyl (acetamide (C 0H7F,N () 175277-96-0) see Mabutcrol /V-(4-cyano-3-trifluoromethylphenyl)-3-(fluorophenyl-sulfanyl)-2-hydroxy-2-methylpropionamide (C,hH14F4N202S 90356-78-8) see Bicalutarnide 2-cyano-3-(3,4,5-trimethoxyphenyl)-2-propcnoic acid ethyl ester... 

Monoterpene Bases.—Yohimbine-Corynantheine (and Related Oxindoles)-Pier aline Group. It is well known that 3,4-dehydroyohimbane (35a) is reduced by zinc-acetic acid to a mixture of yohimbane (35c) and i/ -yohimbane (35d) however, when 10-methoxy-3,4-dehydroyohimbane (35b) was similarly treated, a 2,3,4,7-tetrahydro-derivative (17 % yield) was formed as well as the corresponding 10-methoxy-yohimbanes. It was shown that this did not arise by further reduction of either of the methoxy-yohimbanes and no explanation is yet available for this interesting difference. Reserpine, a 6-methoxyindole, underwent C(3)-N(4) bond fission on reaction with zinc-acetic acid, as did indoles with no ring A methoxy-group. Cleavage of the C(3)-N(4) bond with the formation of N(4)-cyano-C(3)-alkoxy- or hydroxy-seco-derivatives was observed when yohimbine, i/ -yohimbine, and methyl reserpate were subjected to von Braun degradation conditions in alcohol or aqueous solution. 

An efficient and rapid method for synthesis of jS-lactams under solvent-free conditions in the presence of a phase-transfer agent (18-crown-6) in a closed Teflon vessel has also been developed by Hamelin et al. [46a]. The same solvent-free approach has also been successfully used by Kidwai et al. for synthesis of N-(4-hydroxycyclohexyl)-3-mercapto-3-cyano-4-arylazetidine-2-ones [40]. The adducts... 

Trifluoromethylquinoline-N-oxide under similar conditions gave 4-cyano-3-trifluoromethylquinoline in 48% yield [91], while 4-nitroquinoline-N-oxide gave (31) on reaction with potassium cyanide and ethyl cyanoacetate [92]. 

Cycloaddition of 2-styryl-4/7-3,l-benzoxazines and malononitrile gave 1 -amino-3-aryl-2-cyano-1 //,6//-pyrido[l, 2-n][3, l]benzoxazin-4-ones (99ZN(B)923). These tricyclic derivatives were also prepared in the reaction of 2-methyl-4//-3,l-benzoxazin-4-one and arylidenemalononitrile in AcOH in the presence of NaOAc. 

A 9 1 mixture of 2,4-difluoro-4-pentafluoroethyl-3-trifluoromethyl-2//-, and 2,4-difluoro-2-pentafluoroethyl-3-trifluoromethyl-4//-, as well as 2-pentafluoroethyl-3-trifluoromethyl-4-oxo-4//-pyrido[l,2-n]pyrimidine were characterized by H, and NMR (00JFC105). 2-Trifluoromethyl-3-cyano-4-imino- and -4-oxo-4//-pyrido[l, 2-n]pyrimidines were characterized by and F NMR (00MI27). 

Acidic hydrolysis of 4-imino-3-cyano-2-trifluoromethyl-4//-pyrido[l,2-n]pyrimidines in boiling EtOH with aqueous hydrochloric acid afforded 4-0X0 derivatives (00MI27). 

Cyclization of 3-cyano-2-[(3-hydroxypropyl)amino]-5-(4-pyridyl)pyri-dine-l -oxide (298) in POCI3 yielded 9-cyano-7-(4-pyridyl)-3,4-dihydro-2/f-pyrido[],2-n]-pyrimidine I -oxide (299) (94EJM175). After heating 3-cyano-4-trifluoromethyl-6-phenyl-2-[(3-hydroxypropyl- and 3-hydroxybutyl)-amino] pyridines in boiling POCI3 for 1 h, the product was treated with aqueous NH4OH to yield 6-phenyl-8-trifluoromethyl-9-cyano-3,4-dihydro-2//-pyr-ido-[l,2-n]pyrimidine and its 4-methyl derivative (01CHE329). 

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). 

Cyclocondensation of 2-aminopyridines and ethyl cyano(hydroxyimi-no)acetate in the presence of NaOEt gave 4-amino-3-nitroso-4//-pyrido[l,2-n]pyrimidin-2-ones 348 (95JHC1725). 

Cyclocondensation of 2-iminopiperidine hydrochloride with an E Z isomeric mixture of ethyl 2-cyano-3-methylsulfanyl-3-( 1,2,4,5-tetrahydro-3/f-benzo[r/ azepin-3-yl)acrylate in DMF in the presence of DBU at 100°C gave 2-substituted 6,7,8,9-tetrahydro-4//-pyrido[l, 2-n]pyrimidine-3-carbo-nitrile (01EUP1074549). 

Preparation of 4-Phenyl-4-Cyano-N-Methyl Azacydoheptane Methobromide A 0.1 M nitrobenzene solution of 1-dimethylamino-3-cyano-3-phenyl-6-bromohexane was kept at 100°C for 1 hour whereby the quaternary salt precipitated out MP 246 to 247 C. 

A solution of 69g of sodium in 1,380 ccof absolute alcohol is mixed with 257.4 g of /3-methyl-thioethyl-d -methyl)-n-butvl-cyano-acetic acid ethyl ester and 114 g of thiourea and the whole mass boiled under reflux with stirring for six hours. After concentration under vacuum the residue is taken up in 1.5 liters of water and shaken up thrice, each time with 300 cc of ether. The aqueous alcoholic layer is stripped, under vacuum, of the dissolved ether and mixed with 300 cc of 30% acetic acid under stirring and ice cooling. The precipitated material is sucked off, washed with water, dried and recrystallized from isopropyl alcohol. The thus obtained j3-methvl-thioethyl-(1 -methyD-n-butyl-cyano-ecetyl thiourea forms yellowish green crystals having a melting point of 229°C to 230°C. 

Interfacial polycondensation between a diacid chloride and hexamethylenediamine in the presence of small amounts of ACPC also yield polymeric azoamid, which is a macroazo initiator.[27] In this manner, azodicarbox-ylate-functional polystyrene [28], macroazonitriles from 4,4 -azobis(4-cyano-n-pentanoyl) with diisocyanate of polyalkylene oxide [29], polymeric azo initiators with pendent azo groups [3] and polybutadiene macroazoinitiator [30] are macroazoinitiators that prepare block and graft copolymers. 

In 2004, Alterman et al. apphed their cyanation protocol to the synthesis of N-(t-butyl)-3-(4-cyanobenzyl)-5-isobutylthiophene-2-sulfonamide [61]. Deprotection of the sulfonamide followed by carbamate formation via reaction with butyl chloroformate finally gave the target compoimd for biological evaluation as a selective angiotensin 11 AT2 receptor agonist (Scheme 65). The cyano derivative, however, showed only a low affinity for the AT2 receptor (Ki value >10 p,M). 

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