Pyrrolo pyrimidin-4-amines

Alternatively, pyrrolo[3,4-d]pyrimidine-2,5-diones were synthesized using the same pyrimidine resin precursor, which was first treated with a representative set of primary amines to substitute the chlorine. Subsequent cyclative cleavage was carried out as described previously, leading to the corresponding pyrrolopyrimidine-2,5-dione products in high purity but moderate yield. 

An interesting pyrrolo[l,2-tf]pyrimidine was described as the product of the reaction of the heterocyclic ketene-aminals 236 that was synthesized by cyclocondensation of ketene dithioacetals 237 and 1,3-diamino propane. These compounds reacted with diethyl oxomalonate that behaves as an hetero-enophile, yielding the corresponding products 238 in acceptable to good yield (Scheme 31). A mechanism that involves an aza-ene reaction, via adduct 239 which isomerizes to ketene aminal 240 to produce the lactam ring of 238, has been proposed <1999J(P1)321>. 

The investigations that describe the syntheses of pyrrolo[2,3-,7 pyrimidines from pyrimidines, with very few exceptions, have nitrogen functionality at the 4/6-position of the pyrimidine ring. Primarily this nitrogen-containing group is an amine moiety. Even within these limits, the major type of pyrimidine precursor has no substituent at position 5. 

The tertiary amine 127 undergoes an interesting reaction with dimethyl acetylenedicarboxylate to produce the partially reduced pyrrolo[2,3- pyrimidine 128 (Equation 47) <1996TL1853, 1998JCM2025>. 

As with other series involving the annulation of a pyrimidine ring onto a five-membered ring, the usual requirement is to have two adjacent functional groups, one of which is an amine. The use of a cyano group as the other functional group occupies the majority of examples in such syntheses. Therefore, it is not surprising that this situation holds in the syntheses of pyrrolo[2,3-,y pyrimidines from pyrroles. 

The same may be said of an amine function adjacent to a ketone, although with a 4-substituted pyrrolo[2,3-r/ -pyrimidine 166 as the end product. Equation (62) illustrates this type of reaction, where 165 is heated with ammonium acetate <1996IZV1720>. 

Although strictly speaking this example does not begin with a preformed ring, the explanation for the conversion of 236 into pyrrolo[3,2-tf pyrimidines 237 by heating with an amine appears to proceed via an unisolated pyrrole (Equation 84) <2000H(53)805>. This process can be explained by cyclization of 236 into 3-dimethylamino-4-(2-pyridinyl)pyrrole-2-carboxylate followed by reaction with another molecule of 236 in which the dimethylamino group is substituted by the aminopyrrole derivative. 

The bromoaldehyde (182) reacts with primary amines to give the pyrrolo[3,4-treatment with hydrazine hydrate is converted into (183 R = NH2) (78S463). The acetonylpyrimidines (184) react with ammonia and primary amines to give pyr-rolopyrimidines, e.g. (185). Nucleophilic displacement of the halogen is probably effected... 

A novel and simple approach to pyrrolo[3,4-with amines and hydrazines, respectively (78S463 ... 

Formyl-6-aminomethyluracil derivatives give imines with primary amines. These are in equilibrium with a 5,6-bisaminomethylene-uracil. Internal cyclization gives pyrrolo[3,4-rf]pyrimidines (89BCJ3043) (Scheme 166). 

A tandem aza-Wittig/heterocumulene-mediated annulation route was developed for the efficient production of 6,7,8,9-tetrahydro-benzothieno[2,3-r/]-l,2,4-triazolo[l,5-a]pyrimidin-10(3F/)-ones <05S1601>, and an amine oxide rearrangement was key to the regioselective preparation of pyrrolo[2,3-J]pyrimidines <0581164>. Hexahydro-2-phenacylidene-pyrimidines gave -lactam fused 8-aroyl-2,3,4,5-tetrahydro-7-hydroxy-6//-pyrrolo[l,2-a]py-rimidine-6-ones when treated with (COCl), in the presence of NaH <05IJH87>, and methyl... 

A one-pot reaction involving an imine intermediate was noted in Section V,D. Related syntheses of pyrrolo[2,3- f]pyrimidines (150), involving preformed anils (149) from condensation of the amines (133) with aromatic aldehydes, are outlined in Scheme 35 (57CB738). 

Thermal cyclization of 350 produced furo[3,4-d]-pyrimidines 351. Prior treatment of 350 with a variety of primary amines, followed by high-temperature microwave heating led to pyrrolo[3,4-d]-pyrimidine 352. While 350 with hydrazine gave pyrimido[4,5-d]-pyridazines 353 (Scheme 133) (02MI6). 

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