Pyrimidine reaction with hydrazine

Reaction of 160 with hydrazine affords the hydrazino derivative 161, which reacts further with hydrazine to yield the pyrazolo [3,4-d] pyrimidine derivative 162. Reaction with hydrazine hydrochloride afforded 163, which was converted into 162 upon treatment with hydrazine (79JHC1109). 

The majority of pyrimido[4,5-c]pyridazines have been prepared from pyrimidine precursors. The chloropyrimidines (176) give the desired heterocyclic ring (177) on reaction with hydrazine (72BSF1483). Hydrazine also reacts with ethyl a-diazo-/3-oxo-5-(4-chloro-2-methylthiopyrimidine)propionate (178) to give the pyrimido[4,5-c]pyridazine-3-carboxamide (78). A mechanism for this interesting reaction has been proposed as shown, on the basis of the detection of hydrogen azide in the reaction mixture. There is no precedent for the reaction of the a-carbon of a-diazo-/3-oxopropionates with nucleophiles under basic conditions (76CPB2637). 

Kurasawa and Takada transformed the 2-oxo-2H-pyrido[l,2-u]pyrimi-dine (30) with phosphoryl chloride-dimethylformamide to the pyrido-[l,2-a]pyrimidine (201) and reacted the latter with methylhydrazine to obtain 4°, of the pyrido[l,2-a] pyrimidine (202) and 78% of the pyridazino-[3,4-b]quinoxaline(203 R = Me, R2 = NMeNH2). Reaction with hydrazine gave the pyridazino[3,4-b]quinoxaline (203 R = H, R2 = OEt).26-27... 

Substitutions can also occur at the 2-position of similar thienopyrimidines <86PHA23,91IJC(B)618>. 2-Methylthiothieno[2,3-(7]pyrimidines undergo reaction with hydrazine in an analogous manner <87KGS1131>. 

Reaction with Hydrazines, Guanidine, and Amidines Synthesis of Pyrazoles and Pyrimidines... 

The reaction of aryl isothiocyanates with pyrrole77 has been applied to the heterocyclic isothiocyanate ethyl 3-isothiocyanatopyridine-2-carboxylate and yields ethyl 3- [(pyrrol-2-yl)-thioearbonyl]amino pyridine-2-carboxylate (9), which can be used for cyclization reactions with hydrazine or methylamine to give the corresponding 3-substituted 2-(pyrroI-2-yl)-pyrido[3,2-[Pg.166]

The diazines are very susceptible to nucleophilic addition pyrimidine, for example, is decomposed when heated with aqueous alkali by a process which involves hydroxide addition as a first step, and it is converted into pyrazole by reaction with hydrazine. 

Mercapto pyrimidines 82 were synthesized from acetoacetanilide, dihydroxybenzaldehyde, and thiourea, which were readily alkylated with benzyl chloride to afford 2-benzylthio derivatives 83 (Scheme 32). 83 when reacted with different amines in acetic acid furnished 2-amino derivatives 84 (R = Ar), whereas upon reaction with hydrazine hydrate 83 afforded 2-hydrazinyl derivative 84 (R = NH2), which with different aldehydes gave hydrazones 85 (R = 2-furyl, 2-thienyl). Arylidene thiazolidinone 86 was obtained from 84 with carbon disulfide, monochloroacetic acid, and aryl aldehydes, while 84 with ethyl acetoacetate and different aromatic aldehydes provided pyrazoles 87 (Scheme 32) (10MI9). Such tetrasubstituted pyrimidines act as cyclin-dependent kinase (CDK2) inhibitors. 

Reaction of 5-chloro-l,2,4-triazolo[l,5-c]pyrimidines (165) with sodium hydroxide, thiourea, or hydrazine hydrate (79AJC1585) or with sodium azide (85EUP152841) also caused the displacement of the chlorine atom to... 

Thiadiazinotriazolopyrimidines can be prepared in several ways from the hydrazine-substituted thiadiazino-pyrimidine 186. Reaction with carbon disulfide gives the thione 187 reaction with either anhydrides or orthoformates with sulfuric acid gives the substituted triazoles 188, and reaction with cyanogen iodide gives the aminotriazole 189 (Scheme 47) <2004HC0335>. 

Synthesis from pyrido[7,2-a/pyrimidines. Reaction of the disubstituted pyridopyrimidinone 416 with hydrazine gives the aminopyrazole-fused product 417 (Equation 153) <1996FA781, 2003JIC311, 2004IJB1561>. Similarly, substituent interaction in the pyridopyrimidine 418 with amines in toluene at reflux gives, in various proportions, diastereomeric mixtures of the pyrrolopyridopyrimidines 419 and 420 (Equation 154) <2003T4581>. 

The reaction of 2-mercapto-4-(2, 4 -dichlorophenyl)-5-cyanopyrimidin-6(l//)one 421 (obtained by stirring ethyl cyanoacetate and thiourea with 2,4-dichlorobenzaldehyde in sodium ethylate at room temperature, in 70% yield), with a solution of monochloroacetic acid and />-cholorobenzaldehyde in glacial acetic acid, in the presence of sodium acetate, affords 2-[(/>-chlorophenyl)methylene]-6-cyano-7-(2, 4 -dichlorophenyl)thiazolo[3,2-tf]pyrimidin-3,5-dione 422. Finally, the reaction of compound 422 with hydrazine hydrate converts it into product 423 (Scheme 49) < 1996PS( 116)39>. 

The pyrimidines cytosine and thymine both react with hydrazine, which initially attacks the unsaturated carbonyl system and then leads to ring opening. Again, base treatment is used to hydrolyse the phosphodiester bond. This reaction becomes selective for cytosine in the presence of NaCl, which suppresses reaction with thymine. 

Ring transformation of ethyl 2,4-dioxo-l,2,3,4-tetrahydropyrido[2,3- pyrimidine-5-carboxylates 317 with 80% hydrazine hydrate in boiling ethanol gave a mixture of 5-methyl/allyl/benzylamino-l,2,3,4-tetrahydro-l,4-dioxopyr-ido[3,4-i/ pyridazines 318, pyrido[2,3,4-< <7]pyridazino[3,4-/ [l,2,4]triazepines 319, and a low yield of 2,3,4,6,7-penta-azaphenalene 320. The reaction of 317 with hydrazine hydrate was also performed without a solvent in an oil bath at 125 °C for 1 h to give the same products, but higher yields of 318 and lower yield of 319 as well as traces of 320 were obtained (Equation 25) <1997FA657>. 

Reaction of 79 with hydrazine gives 80,81, and 82. Both 80 and 81 cyclize to the pyrazolo[l,5-a]pyrimidine 82 with hydrogen chloride (74JHC423). Similarly, 83 is obtained by reaction of 79 with 74 and treatment of the... 

Dicyano-l,3-dimethyluracil (156) undergoes substitution reactions with amines or sodium methoxide to yield 157 (R = NHR or OCH3). Compounds 157 reacted with hydrazines to yield the hydrazino derivative 158, which readily cyclized to the pyrazolo[3,4-[Pg.343]

Reaction of cyanoacetic acid with formamide in hot acetic anhydride affords a product assumed to be 164. This with triethyl orthoformate gives the vinyl ether 165. The latter reacts with hydrazines to yield 166. Heating hydrazine 166 (R = H) gives pyrazolo[3,4-d]pyrimidines 167 and 168 the hydrazine 166 (R = CHsOr Ph) gives the pyrazole 169 and then 168 on heating (71JCS(C)1610). 

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