Pyrimidines trifluoromethyl

Trifluoromethyl-substituted dioxazine or pyrimidine derivatives are obtained oriK3.cliQn oihexafluoroacetone with cyanoguanidines [93] orcyanoacetamides... 

Bis(trifluoromethyl)-substituted pyrimidines are also available fromtrifluoro-acetonitrde on reaction with enamines and ynamines [d ] With dimethylami-nocrotonates, a cyclocondensation takes place to give 2-pyridones. 5-Cyano-6-trifluoromethyluracil is available via a similar route [95] (equation 18)... 

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). 

Heating 6-bromo- and 6-chloro-2-halomethyl- (99JHC1065) and 6-bromo-, 6-chloro- and 6-fluoro-2-phenyl-4/f-pyrido[l, 2-u]pyrimidin-4-ones (00JMC2814) in phenyl ether at 220 °C for 10 min yielded the appropriate 7-halo-1,8-naphthyridin-4-ols. 6-Amino-2-trifluoromethyl-4//-pyrido[l, 2-a]-pyrimidin-4-one was transformed into 7-amino-2-trifluoromethyl-l,4-dihy-dro-l,8-naphthyridin-4-one in 90% yield (98EJM383). 

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 ethyl (V-(cyanoacetyl)urethane with trifluoroacetonitrile gave 5-cyano-6-trifluoromethyluracil (85JOC4642). Trifluoroacetonitrile reacted with benzyl cyanide (86JOU1408) and diethyl malonate (89JHC7) to yield 2,6-bis(trifluoromethyl)pyrimidines. Cycloaddition of trifluoroacetonitrile with enamines having a /3-H offered a general route to 2,4-bis(trifluoromethyl)pyrimidines (84LA991). 

The crystal structures of 4-phenyl-2- 4-[4-(2-pyrimidinyl)piperazin-l-yl]butyl -2,3,5,6,7,8-hexahydro-177-pyrido[l,2-c][l,3]oxazine-l,3-dione <1995ZK899>, 4-cyano-l-phenyl-l-trifluoromethyl-2,3-dihydro-l/7-pyrido[l,2-r-]pyrimidin-... 

Reaction of 2-cyanomethylpyridine with iV-(l-aryl-l-chloro-2,2,2-trifluoroethyl)-iV -(4-methylphenyl)carbodiimides, and with (1,1,2,2,2-pentachloro- and l,l-dichloro-2,2,2-trifluoroethyl)isocyanates or A-methoxycarbonyl-l,2,2,2-tetrachloro-, — l-chloro-2,2-trifluoroacetaldehyde imines afforded 3-aryl-4-cyano-l-(4-methylphenyl)imino-3-trifluoromethyl-2,3-dihydro-17/-pyrido[l,2-f]pyrimidines and 4-cyano-3-trichloro-, 4-cyano-3-trifluoro-17/-pyrido[l,2-4pyrimidin-l-ones, respectively <2004CHE47>. Refluxing 2-cyanomethylpyridine and iV-(l-aryl-l-chloro-2,2,2-trifluoroethyl)isocyanates in benzene furnished l-aryl-4-cyano-l-trifluoromethyl-l,2-dihydro-3//-pyrido[l,2-4pyrimidin-3-ones. However, when the solution of the isocyanate was added dropwise to the solution of 2-cyanomethylpyridine, and the reaction mixture was then treated with NEt at room temperature, the isomeric 3-aryl-4-cyano-3-trifluoromethyl-2,3-dihydro-l//-pyr-ido[l,2-dpyrimidin-l-ones were obtained. Reaction of l-(acetyl- and benzoylmethylene)-6,7-dimethoxy-l,2,3,4-tetra-hydroisoquinolines with PhCONCS yielded 1-acetyl-, 1 -benzoyl-9,10-dime thoxy-3-pheny 1-6,7-dihydro-2//-pyrimido[6,l- ]isoquinoline-2-thiones <2003SL2369>. 

Cyclocondensation of 2-iminopiperidine and 3-aryl-2-propynylnitriles afforded 4-aryl-2-imino-6,7,8,9-tetrahydro-22/-pyrido[l,2- ]pyrimidines <20000L3389, 2002W002/00629>. The minor isomers, 2-aryl-4-imino-6,7,8,9-tetrahy-dro-4/7-pyrido[l,2- ]pyrimidines could also be isolated in 2-30% yields from the reaction mixtures <20000L3389>. When the reactions were carried out in the presence of 2 equiv of NaHMDS, the product ratio was reversed. From the reaction mixture of 2-aminopyridine and perfluoro-2-methylpent-2-ene in MeCN, a 9 1 mixture of 2,4-difluoro-2-pentafluoroethyl-3-trifluoromethyl-477- and the isomeric 2,4-difluoro-4-pentafluoroethyl-3-trifluoromethyl-277-pyr-ido[l,2- ]pyrimidine (64%), and 2-pentafluoroethyl-3-trifluoromethyl-47/-pyrido[l,2- ]-pyrimidine-4-one (20%) was isolated <2000JFC(103)105>. 

A series of 2-(5-aryl-3-styryl-4,5-dihydro-lA-pyrazol-l-yl)-4-(trifluoromethyl)-pyrimidines 78 was synthesized by the cyclocondensation of 5-aryl-l-carboxamidino-3-styry 1-4,5-dihydro-1 //-pyrazoles 76 with 4-alkoxy-l,l,l-trifluoroalk-3-en-2-ones 77 <06S2349>. 

Microwave-assisted regiospecific shyntesis of 2-trifluoromethyl-7-trihalomethylated pyrazolo[l,5-a]pyrimidines has been reported <06MI358>. A one-step synthesis of pyrazolo[ 1,5-a]pyrimidine via an intermolecular aza-Witting reaction has been achieved <06JHC523>. 

A series of antimicrobial pyrazolo[3,4-<7]pyrimidines containing 8-(trifluoromethyl)quinoline have been synthesized from 5-amino-1-[8-... 

Dihydropyrimidines are normally readily oxidized to the corresponding pyrimidines by dehydrogenation, hydrogen transfer, or disproportionation reactions <1994HC(52)1, 1996CHEC-II(6)93>. For example, the oxidation of a series of trifluoromethyl ketones 522 with DDQ occurred readily at room temperature <1997H(44)349>. Facile room temperature oxidation with ceric ammonium nitrate (CAN) has also been achieved <2003ARK(xv)22>. 

Oxazines and 1,3-thiazines have been used quite extensively as substrates in pyrimidine syntheses <1994HC(52)1>, and an improved procedure for the synthesis of 6-trifluoromethyluracil derivatives 956 from 2-dimethylamino-4-trifluoromethyl-l,3-oxazine-6-one 955 has been developed using DBU in xylene <2000USP6140270, 2002USP6355796>. 

Methyl 5-(3-fluorophenyl)-7-methyl-l,2,3,4,5,8-hexahydropyrido[2,3-tetrahydro derivative 137 by the action of sodium nitrite in acetic acid <1994T8085>. Oxidation of 2,7-disubstituted-5-trifluoromethyl-l,2-dihydropyrido[2,3-r/]pyrimidin (3//)-ones using active Mn02 in CH2CI2 gave the corresponding pyridopyrimidin-4(3//)-ones 138 <1995IJB587>. 

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