Pyrimidine, 2 chloro 2 dimethylamino

Reaction of 9-[chloro(dimethylamino)methylene]tetrahydropyrido[l, 2-a]pyrimidin-4-ones 608 and aldimines or ketimines 609 in chloroform and acetonitrile gave a diastereomeric mixture of tricyclic compounds 611 and 612 at room temperature (82BEP892120, 82TL2891). The formation of compound 610 and the formation of a 1 1 mixture of the tricyclic products 611 and 612 could be detected by H NMR spectroscopy (82TL2891). After refluxing the reaction mixtures, only the thermodynamic product 611 could be isolated in pure form. 9-[Chloro(dimethylamino)methylene] derivatives 608 (R = CN, COOEt) also reacted with cyclic imines to yield the corresponding tetra- and pentacyclic quaternary salts, similar to 611 and 612 (87H2615). 

Note Despite the large variety in substituents in the pyrimidine ring, dimethylamino (+1), chloro (-1) and oxo (-M), the respective purine-8-ylidene ligands were remarkably similar in their electronic properties (A vCO of cm- ) [102],... 

Pyrimidine 6-Chloro-4-((chloro-dimethylamino-methylen)-amino]-5-cyan-2-dimethylamino-E9b/1, 11 ((H2N)2C = C(CN)2 4-R2 =CC12]... 

Chloro-2-(dimethylamino)pyrimidine was reacted with diethyl aminomethylenemalonate in ethanol in a sealed tube at I40°C for 6 hr to give 4-pyrimidinylaminomethylenemalonate (281) in 73% yield (72USP3673184). 

Catalytic reduction of 7-(l-chloroalkyl)-8-chloro-9-[(dimethylamino-methylene)amino]-4-oxo-4//-pyrido[ 1,2-a]pyrimidine-3-carboxylate 331 over 10% palladium-on-charcoal with hydrogen in acetic acid gave 7-alkyl-9-[(dimethylaminomethylene)amino]-4-oxo-4//-pyrido[l,2- ]pyrimidine-3-carboxylates 332 (91H1455). 

This high-pressure methodology was later used by several groups, e.g., for the preparation of 4-(dimethylamino)pyridine (DMAP) derivatives [91] and oligoanilines [92]. More intriguingly, the synthesis of enantiomerically pure C-6 substituted pyrazolo[3,4-d]pyrimidines 147 has been performed by SNAr reaction of 4-amino-6-chloro-l-phenylpyrazolo[3,4-d]pyrimidine (145) under high-pressure conditions at ambient temperature. Conventional synthetic conditions (reflux at 0.1 MPa) were unsuccessful. The S enantiomer displayed higher affinity and selectivity for the adenosine Al receptor than the R enantiomer (Scheme 40) [93]. 

Pyrimidine 6-Chloro-5-cyano-2-dimethylamino-4-ethoxycarbo-nyl- E9b/2, 23 [(NC)2C=CC1-COOC2 + R2N-CN]... 

Typical preparations have been described for 2-(r-hydroxyiminomethyl)pyrazine (138) 2-(4 -dimethylamino-T-hydroxyiminobutyl)pyrazine (1186) 2-(2 -hydroxy-iminopentyl)-6-methylpyrazine (645) 2-(2 -hydroxyimino-3, 3 -dimethylbutyl)-6-methylpyrazine (645) 2-[r-hydroxyimino-2-(pyridin-2"-yl) (hyl]pyrazine (642) 2-[2 -hydroxyimino-2 -(pyridin-2"-yl, pyrazin-2"-yl, or pyrimidin-4 -yl)ethyl]pyrazine (642) 2-[l, 2 -bishydroxyimino-2 -(pyridin-2"-yl)ethyl]pyrazine (642) 2-12 -(2",4"-dinitrophenylhydrazono)-3 -methylbutyl]-6-methylpyrazine (645) 2-[ 1-(substituted hydrazono)ethyl]pyrazine (1196) 2-[l -phenyl-1 -(substituted hydrazono)methyl]-pyrazine (1196) 2-(r-thiosemicarbazonoethyl)pyrazine (138) 2-(2 -chloro-l -thiosemicarbazonoethyOpyrazine (138) and 2,5-dimethyl-3,6-bis(r-semicarbazono-ethyl)pyrazine (1196). 

Ethyl 4,5-diamino-2-(dimethylamino)thieno[2,3-z/]pyrimidine-6-carboxylate (142) was prepared in 93% yield from 4-amino-6-chloro-2-(di-methylamino)pyrimidine-5-carbonitrile (143) with ethyl 2-mercaptoacetate in refluxing EtOH-THF (5 1) (2000S255). 

Other synthons for 1,3-dicarbonyl compounds that have been successfully applied include p-chloro-a,P-unsaturated ketones and aldehydes, P-dimethylamino-a,P-unsaturated ketones (easily obtained from ketones by reaction with DMFDMA), P-alkoxy-enones"" and vinyl-amidinium salts."" Alkynyl-ketones react with 5-alkyl-isothioureas, giving 2-alkylthio-pyrimidines" and propiolic acid reacts with urea to give uracil directly in about 50% yield. "" 1,3-Keto-esters with formamidine produce 4-pyrimidinones"" and C-substituted formamidines with ethyl cyanoacetate give 2-substituted-6-amino -pyrimidinones. In analogy, pyrimidines fused to other rings, for example as in quinazolines, can be made from ortho-aminonitriles " and in general, from P-enamino esters. ... 

Glycine ethyl ester hydrochloride (5.5 g, 39 mmol) in DMF (15 mL) was refluxed for 15 min with NaOMe (2.1 g, 39 mmol) in a sealed tube. The mixture was then added to 4-chloro-5-(4-chlorophenyldia7Cnyl)-2,6-bis(dimethylamino)pyrimidine (3.4 g, 13 mmol) in DMF (20 mL) and the mixture heated for 15 min at 60- 70 C. After standing overnight the precipitate was collected, washed with EtOH, then suspended in H20 and filtered. The Solid (3.0 g) was suspended in HOAc (30 mL) and Zn dust (2.4 g) was added. The mixture was relluxed for 1 h then after cooling, the precipitate was collected, washed with HOAc and filtered. The filtrate was evaporated to dryness and the residue was boiled with HzO (10 mL) and after neutralizing and cooling the precipitate was collected (0.98 g). 

Aryl-6-phenyl-2-methylthio/secondary amino substituted-4(3//)-pyrimidinones were derived from a reaction of N-arylamino substituted 1,3-diaza-1,3-butadienes with substituted ketenes that was analyzed by computational methods <97T13829>. 1,3-Diazines related to 6-amino-4-chloro-5-cyano-2-(dimethylamino)pyrimidine were prepared in one-pot fashion from 1,1-diamino-2,2-dicyanoethylene and phosgeniminium chloride <97SC1223>. Pyrazolo[3,4- /]pyrimidines were derived from 4-substituted 5-aminopyrazole-l-carbothioamides <97JCR(S)352>. Amino-5-(trifluoromethyl)-l,2,4-triazole gave polysubstituted 2-... 

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