Alkyl halide with pyrimidines

Trifluoromethylation is the most important perfluoroalkylation reaction. Kobayashi and co-workers reported the trifluoromethylation of aryl, vinyl, alkyl halides with trifluoromethyl iodide in the presence of copper powder in aprotic solvents such as HMPA at 120-150 °C [83,84], and this methodology has been applied to the preparation of fluorinated pyrimidine and purine nucleosides [85,86] (Scheme 27). 

In the presence of potassium carbonate, alkyl halides reacted with the imidic acid tautomers 154 of l,2,4-triazolo[l,5-c]pyrimidin-2-ones (153) to afford the 2-alkoxy derivatives 155 (85USP4528288 94JMC2371) (Scheme 60). 

Dihydro-2//-pyrido[l,2-a]pyrimidines were quaternized with alkyl halides or benzyl chloride.188,189,193... 

As has already been pointed out, the Finkelstein reaction can be conducted in situ in the absence of solvents. For example, alkylations of purine and pyrimidine bases with alkyl halides and dimethyl sulfate have been carried out by solid/liquid phase-transfer catalysis in the absence of any additional solvent [48], as have cyanation of haloalkanes [49] and / -eliminations [50]. Noteworthy is the synthesis of glycosyl isothiocyanates by the reaction of potassium thiocyanate with molten glycosyl bromide at 190 °C [51]. 

Thieno[3,2-d]pyrimidine-2(l//)-thiones 217-219 and -4(3//-thiones 245 were S-methylated smoothly with methyl iodide in base to the corresponding 2-methylthio (82EUP43054 89CPB1197) and 4-methylthio (86JHC 1757) compounds. 5-Alkylation of thieno[3,2-d]pyrimidin-4(3//)-one-2(l//)-thione 223 with alkyl halides in dilute sodium hydroxide solution afforded 2-alkylthio derivatives 284. Nucleophilic displacement of the alkyl-thio group in compound 284 by primary amines has also been reported (90EUP404356). 

Substituted thieno[3,4-d]pyrimidine-2(l//),4-diones 306 and 312 were alkylated at position 1 with alkyl halides, in DMF, DMSO or THF, in the presence of sodium hydride (87USP4670560 88JMC1786 90JHC1761 91 Mil). The alkylation of compound 303 with ethyl bromoacetate in DMF in the presence of sodium hydride produced derivative 381 (93MI1). Alkylation of N-3-protected thieno[3,4-d]pyrimidine 320 with l-bromo-2-chloroethane in dimethyl sulfoxide containing sodium hydride, afforded 1 -(2-chloroethyl)-3-(2,4-dime thoxyphenylmethyl)thieno [3,4-d] pyrimidine-... 

The reaction of the salt 308 with alkyl halides in base gave the corresponding 2-alkylthiothieno[3,4-d]pyrimidin-4(3//)-ones 369. Heating the latter with ammonia or amines afforded 2-amino(or substituted amino)thieno[3,4-d]pyrimidin-4(3//)-ones 370 (90EUP404356). When 2-methylthiothieno[3,4-d]pyrimidin-4(3//)-one 360 was heated with o-tolu-idine at 200°C, displacement of the 2-methylthio group afforded compound 372 (91MIP1). 

A one-pot procedure was developed (2001JHC419) for the synthesis of (2-al-kylthio-4-oxothieno[3,2-[Pg.87]

N-Alkylation of triazolopyrimidines has been made with dialkyl sulfates or alkyl halides in alkaline media. Alkylation of the 2-oxo- and 5-oxo-l, 2,4-triazolo[4,3-c]pyrimidines 25 and 92 took place at the nitrogen atom adjacent to the carbonyl function in each case to give the N2-alkylated 91 (68JOC530 94JMC2371) and N6-alkylated derivatives 93 (60G1821 ... 

Methylsulfanyl)-5-oxo-5,8-dihydropyrido[2,3-cf]pyrimidine-6-carboxylic acid is alkylated at N8,325 as is ethyl 4-acetamido-2-(methylsulfanyl)-5-oxo-5,8-dihydropyrido[2,3-(/]-pyrimidine-6-carboxylate (5)326 or ethyl 5-oxo-5,8-dihydro-2-pyridylpyrido[2,3-t/]pyrimidine-6-carboxylate196 by treatment with an appropriate alkyl halide in dimethylformamide/ potassium carbonate. 

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