Pyrimidine 2-chloro-4-methyl

Reaction of 2,4-diamino-6-oxo-pyrimidine with methyl 4-(3-chloro-2-oxopropyl)benzoate gives a mixture of 5- and 6-benzyl furo[2,3- 1pyrimidines in 27% yield and 23%, respectively <2006BMC8590>. 

Polystyrene-bound isothiuronium chloride, which is readily prepared from chloro-methyl polystyrene and thiourea, has been used as a starting material for the preparation of various substituted pyrimidines (Entries 9-11, Table 15.28). After oxidation to the corresponding sulfones, nucleophilic cleavage with amines proceeds smoothly to yield substituted 2-aminopyrimidine derivatives (see Section 3.8). 

Contact time very much controls the degree of conversion of polychlorinated pyrimidines heated in sealed tubes with solid potassium fluoride [81 JFC( 17)385], and selectivity can also be achieved by careful control of reaction conditions and reagents. With 2,4,5-trichloropyrimidines, substituted at C-6 by chloro, methyl, chloromethyl, di- or tri-chloromethyl, sodium or potassium fluoride use only resulted in nuclear fluorination. 

The introduction of steric constraints in these ligands can enforce meridional coordination of the three central donors and trara-coordination of the terminal thiolate donors. The use of ligands with pyrimidinyl substituents such as (54), a neutral S2N5-donor obtained in situ from 2,6-bis(chloro-methyl)pyridine and sodium pyrimidine-2-thiolate in dmf, opens the way for the synthesis of coordination polymers.70... 

Uracils undergo a range of electrophilic substitution reactions such as halo-genation, phenylsulfenylation, mercuration, and hydroxy- and chloro-methylation. Bromination of uracils has been shown to proceed via the bromohydrin adduct, and similarly of pyrimidin-2-one, via the bromohydrin-hydrate. ... 

Pyrrolo[2,3-d]pyrimidine, 5-cyano-bromination, 4, 506 Pyrrolo[2,3-d]pyrimidine, 5-nitroso-nucleophilic reactions, 4, 507 Pyrrolo[l, 2- c]pyrimidine-3-carboxylic acids methyl ester synthesis, 4, 293 Pyrrolopyrimidine-2,4-diones Mannich reaction, 4, 504 Vilsmeier reaction, 4, 505 Pyrrolopyrimidines synthesis, 4, 514, 517, 524, 527 Pyrrolopyrimidines, chloro-nucleophilic attack, S, 312 Pyrrolo[2,3-d]pyrimidines NMR, 4, 500... 

Methyl and 6-methyl-5-n-propyl substituted 2,4-dimethoxy-pyrimidines react with methyl iodide, as does the simple dimethoxy compound, to give methoxypyrimidones, but the 6-chloro-2,4-dimethoxy derivative (47) is affected only at 100°, when it gives 4-chloro-1,3-dimethyluracil (48). ... 

These pyridazines are subject to direct deactivation of the leaving group. It would appear from the conditions used in its reactions with ammonia (115°) and methylamine (50°) that 4-chloro-2-ethylthiopyrimidine (225) is somewhat deactivated (indirect). In various aminations of pyrimidines, the effect of an alkylthio group seems to be very mildly deactivating, like that of methyl groups. However, these surmises from the conditions used are not as reliable as the direct qualitative comparison described above and the kinetic data. 

Chloropyrimidine is aminated with alcoholic ammonia at 130° while 4-chloro-2-methyl- and 4-chloro-6-methyl-pyrimidine yield the corresponding 4-amino derivatives at 100°. 4-Aminopyrimi-dine is not prepared from the chloro analog because of facile self-quatemization (see Section III, B, 2 for comments on factors involved) of the latter. 

The chloro atom of 2-[4-(6-chloronicotinoyl)benzyloxy]-3-methyl-4//-pyrido[l,2-n]pyrimidin-4-one, its 6-methyl derivative and 2-[4-(6-chlo-ronicotinoyl)benzylthio]-3-methyl-4//-pyrido[l,2-n]pyrimidin-4-one was replaced by a 4-piperidinopiperidino and 4-phenylpiperazino group with 4-piperidinopiperidine and 4-phenylpiperazine (96EUP733633). The carboxyl group of 2-[4-(4-carboxybenzoyl)benzyloxy]-3-methyl-4//-pyrido[l,2-n]pyrimidin-4-one, prepared by hydrolysis of methyl ester in DMF with 1 N NaOH, was reacted first with diethyl pyrocarbonate in DMF at room temperature and then with 4-phenylpiperazine and 4-piperidinopiperidine to give the appropriate amide derivatives (96EUP733633). 

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