Pyrimidines ethylene derivs

Reaction of 2-chloromethyl-4//-pyrido[l,2-u]pyrimidine-4-one 162 with various nitronate anions (4 equiv) under phase-transfer conditions with BU4NOH in H2O and CH2CI2 under photo-stimulation gave 2-ethylenic derivatives 164 (01H(55)535). These alkenes 164 were formed by single electron transfer C-alkylation and base-promoted HNO2 elimination from 163. When the ethylenic derivative 164 (R = R ) was unsymmetrical, only the E isomer was isolated. Compound 162 was treated with S-nucleophiles (sodium salt of benzyl mercaptan and benzenesulfinic acid) and the lithium salt of 4-hydroxycoumarin to give compounds 165-167, respectively. 

Nucleophilic attack with electron-rich arenes and ethylene derivatives at C-7 of 5-methoxyfuroxano[3,4-d -pyrimidine 245 leads to 7-substituted 6,7-dihydro-5-methoxyfuroxano[3,4-r/]pyrimidines 246 (Equation 47) <2003JP0431>. 

Of greater versatility is an extension of Albert and Royer s acridine synthesis. The first successful use of this in the quinazoline series was for the removal of the chlorine atom in 2-chloro-4-phenylquin-azoline, although it had been used previously to prepare 8-nitro-6-methoxyquinazoline in very poor yield. The 4-chloroquinazoline is converted to its 4-(A -toluene-p-sulfonylhydrazino) quinazoline hydrochloride derivative which is decomposed with alkali in aqueous ethylene glycol at lOO C (Scheme 13). The yields are high (60-70%) when R is Me, Cl, OMe but low when R is NO2, and in the latter case it is preferable to use dilute sodium carbonate as the base. This reaction is unsatisfactory if the unsubstituted pyrimidine ring is unstable towards alkali, as in 1,3,8-triazanaphthalene where the pyrimi-... 

Reduced pyrimidines are much less stable toward hydrolysis than the fully conjugated analogs, and this is often used synthetically to produce amino acids and diamines. The BH3 reduction of cyclic amidines (1,4,5,6-tetrahydropyr-imidines) to hexahydropyrimidines, and their subsequent hydrolysis was mentioned above <1999JFIC105>, but there are many more examples. For instance, m-cyclobutane /5-amino acids 544 can be prepared from the cyclobutane derivatives 542 formed by the [2-F2] photocycloaddition reaction between uracil and ethylene <2002TL6177, 2004TL7095, 2006SL1394>. 

Perhydropyrido[l,2-a]pyrimidine (282) can be converted in an acetic anhydride-formic acid mixture to the 1-formyl derivative, and the 1-formyl group can be reduced to the methyl group with lithium aluminum hydride.342 Treatment with ethylene oxide in the presence of sodium hydroxide leads to the l-(2-hydroxyethyl) derivative,342 and heating with diethylaminoethyl chloride in acetone in the presence of triethylamine gives the l-(2-diethyl-aminoethyl)perhydropyrido [ l,2- ]pyrimidine.27 6,27 7... 

The cyclization of 3-[2-[4-[(2-fluorophenyl)-(2-phenylhydrazono) methyl]-l-piperazinyl]ethyl]-2-methyl-4/7-pyrido[l,2-a]pyrimidin-4-one 452 in boiling ethylene glycol in the presence of potassium carbonate overnight gave indazole derivative 453 in 25% yield (90EUP353821, 90USP4957916). Ocaperidone 8 was obtained when the Z oxime 454 was stirred in toluene in the presence of aqueous potassium hydroxide at 45-55°C for 0.5 hour, then at reflux for 3 hours (91EUP453042). 

Reduction of pyrimidine nucleosides to their 5, 6 -dihydro derivatives by various reagents has been discussed (see p. 293). As stated previously (see p. 290), reduction of the ethylenic linkage at C5 -C6 renders the nucleoside susceptible to cleavage at the glycosyl link by dilute mineral acid. It is noteworthy that, as of this date, conclusive experimental evidence which would provide an explanation of the observed stability of pyrimidine nucleosides toward dilute acids is still lacking. 

The parent compound, perhydropyrrolo[l,2-a]pyrimidine (428), is obtained by the reaction between 4-chlorobutanal and 1,3-diaminopropane in the presence of potassium carbinate (83TLI559). A study of ring-chain tautomerism in such systems shows that in neutral aqueous solutions 428 predominates [84ACS(B)526]. 6-Propyl and 6-heptyl derivatives (430) were prepared by reduction of429 with LiAIH4. Hydroxyethylation of 430 with 50% excess ethylene oxide gives rise to 431 (76URP527433). 

Monaharan has developed a versatile synthetic route for the synthesis of 2 -0-[(N, iV-dimethylamino)-oxyethyl] modified purine and pyrimidine nucleoside phosphoramidites (63a-d) to be used as antisense oligonucleotide building blocks. In the syntheses of the purine-based analogues, the (iV, N-dimethylamino)-oxyethyl group was introduced via a 2 -allyloxy nucleoside intermediate, while the pyrimidine-based nucleosides were obtained from the TBDMS-protected 2,2 -anhydro-5-methyluridine via ring opening reaction in the presence of borane and ethylene glycol. The aminoxy derivatives were... 

Reacting ethylene glycol monobenzoate 635 with acetaldehyde and HCl gas gave 636, whose reaction with pyrimidine derivatives followed by de-benzoylation gave 637 (86JHC1651). The base-catalyzed hydrolysis of 6-substituted 9-(l-ethoxyethyl)purines takes place by nucleophilic attack of hydroxyl ion on C-8 of the purine moiety [82ACSA(B)707],... 

Functionalization of UPy derivatives in order to prepare bi- or multifunctional telechelics is not limited to reactions on the ureido-substituent, but may also use a functionality at the 5- or 6-position of the pyrimidine ring (Scheme 2). Oleflnic UPy derivatives have been obtained by condensation of an ethylenically unsaturated /3-ketoester with guanidine. The resulting UPy 2f has been used to end-functionalize telechelic poly(dimethylsiloxane) via hydrosilylation with a Karstedt s catalyst [17]. 

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