Pyrimidine, 5-bromo-, reaction with

Pyrimidine, see also azines amino-, reactions of, 234 4-amino-2-methyl-, 137 anilino-dechlorination of, 274 benzo-fusion, effect of, 350 6-bromo-, reaction with piperidine, 143... 

Reaction of 9-bromo-2-morphohno-4//-pyrido[l, 2-n]pyrimidin-4-ones with 4-vinylpyridine in DMF at 80 °C for 16 h in the presence of CS2CO3 and PdCbCdppf), and with amines and phenols in boiling THF for 20 h in the presence of KOr-Bu and PdCbCdppf) yielded 9-[2-(4-pyridyl)vinyl), 9-(substituted amino), and 9-aryloxy derivatives, respectively (01MIP9). 4-Hydroxyaniline gave a 9-(4-hydroxyphenyl)amino derivative. 

Uracils and related pyrimidines undergo oxidative addition to the 5,6-double bond, and the reaction with a number of oxidants to form 5,6-epoxides and 5,6-diols was discussed in CHEC-II(1996) <1996CHEC-II(6)93>. Oxidative halogenation can also occur <1996SC3583, 1998NN1125>, as shown by the formation of 5-bromo-5,6-dihydro-6-methoxyuracil 100 from uracil 99 by treatment with a mixture of potassium bromate and potassium bromide in the presence of Dowex ion-exchange resin in methanol <1996SC3583>. 

One final reaction of the ANRORC type which is of some limited synthetic utility is the conversion of certain 6-substituted 2-bromopyridines into pyrimidines by treatment with sodamide in liquid ammonia (e.g. equation 192). Here, the postulated mechanism involves addition of amide ion at the 4-position, ring opening by cleavage of the C(3)—C(4) bond and loss of the 2-bromo substituent, and ring closure of the acyclic intermediate thus obtained. 

Chloro, 3-bromo, 3-iodo, and 3-nitro derivatives of 5,7-dimethyl-pyrazolo[l,5-a]pyrimidine derivatives were prepared by chlorination, bromination, iodination, and nitration of 3-unsubstituted 5,7-dimethyl-pyrazolo[l,5-a]pyrimidines. Reaction with bromine and potassium thiocyanate gave a 3-thiocyanato derivative, which was converted into the mercapto derivative upon saponification. Nitrosation gives the 3-nitroso derivative and acylation with trifluoroacetic anhydride affords the trifluoroacetyl derivative (74JMC645 77JMC386). 

Condensation of 2-hydrazinopyrimidine (384) with an aromatic aldehyde formed the Schiff bases (386), which then cyclized with bromine to 6-bromo-l,2,4-triazolo[4,3-a]pyrimidine (383) and with carbon disulfide to 387 (92PS145). A similar cyclization was effected also on 384 to give 388 (68T2839 85FRP2549834), but the cyclization of 384 or 385 with carbon disulfide afforded 3-thiolo-l,2,4-triazolo[4,3-a]pyrimidin-7-ones 389 and 390, respectively. A small amount of the isomeric 3-thiolo-l, 2,4-triazolo[4,3-a]pyrimidin-5-one was isolated in the former case (68T2839). Reaction of 385 with benzaldehyde [67JCS(C)498] or p-chlorobenzaldehyde (90MI3) followed by oxidation with LTA in benzene afforded 391 (Scheme 73). 

The halogen metal exchange reaction between 7-bromo or 7-iodo-3-phenyltriazolopyrimidine 165 and butyllithium in iV,N,N, N -tetra-methylethylenediamine afforded the 7-lithio compound 166, whereas a similar reaction with the 7-chloro derivative 165 (R = H) gave the ring-fission product, 5-amino-l-phenyl-l//-l,2,3-triazole-4-carbonitrile 169 (91 CPB2793). Reaction of 166 with electrophiles such as benzaldehyde and ketones gave 170 and 167 respectively, together with 7,7 -bis[3-phenyl-3//-1,2,3-triazolo[4,5-d]pyrimidine] 168 (Scheme 34). 

Cyclization with 1,3-dicarbonyl compounds can give high yields of fused pyrimidines [2249, 2722] the halogen of 3-bromo-2,4-pentanedione (which would be expected to be labile) survives the reaction with a 3-aminopyrazole to give a fused bromodimethylpyrimidine in good yield [3426]. 

The NH group in the 3-position of 2-methylpyrido[2,3-fif pyrimidin-4(3//)-one has been used for Mannich condensations with formaldehyde and piperidine or alkylated by a variety of chloro compounds after conversion into the anion by sodium amide.82,328-330 Applying the Mitsunobu reaction with iodomethane to 6-bromo-2-(pivaloylamino)pyrido[2,3-t/]pyrimidin-4(3//)-one results in methylation of Nl.331... 

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