Pyrrolo pyrimidine-6-carboxylates

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... 

Cyclization of diethyl N-[cyclohepta(6)pyrrrol-2-yl]aminomethylene-malonates (1676), by heating in xylene, t-butylbenzene, or tetralin at reflux temperature, gave cyclohepta[4,5]pyrrolo[l, 2-a]pyrimidine-3-carboxyl-ates (1677) in 46-90% yields (87BCJ1053). Cyclization were also carried out in a mixture of phosphoryl chloride and polyphosphoric acid. While compound 1676 (R = COOEt) gave 1677 (R = COOEt) in 95% yield, the unsubstituted 1676 (R = H) afforded a mixture of 1677 (R = H) and 4-hydroxycyclohepta[4,5]pyrrolo[2,3-b]pyridine-3-carboxylate (1678) in 7% and 48% yields, respectively. The nitrogen bridgehead compound (1677, R = H) could not be transformed into pyridine derivative (1678). 

In an effort to explore the chemistry of pyrrolodiazines and their quatemized salts (see Section 6.2.2.2), Alvarez-Builla and co-workers prepared a series of pyrrolo[l,2-c]pyrimidines via methodology developed in their laboratory <99JOC7788>. Cyclocondensation of tosylmethyl isocyanide with substituted pyrrole-2-carboxaldehydes 17 produced pyrimidine derivatives 18 sifter removal of the tosyl group. The key to this procedure was the use of tosylmethyl isocyanide, which provided a relatively easily removed tosyl group in comparison to the more problematic decarboxylation of a carboxylic acid functionality. 

When an amino group is adjacent to a carboxamide group, annulation usually leads to a pyrrolo[2,3-r/ pyrimidin-4-one 164. Such is the case when 163 is allowed to react with aliphatic carboxylic esters (Equation 61) <1996H(42)691>. 

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. 

Finally, ortho aminoesters have been used to produce 7-deazaxanthines. For example ethyl 2-amino-5-phenyl-l//-pyrrole-3-carboxylate is first treated with 2-chloroethyl isocyanate in refluxing toluene. The resulting urea derivative is then allowed to react with l-(2-methoxyphenyl)piperazine and cyclized to the expected pyrrolo[2,3-,7 pyrimidin-2,4(177,377)-dione <2006BMCL150>. 

Neoefrapeptins, neoefrapeptin A Ac-Pip-Aib- Pip- Iva-Aib- Leu-/3 -Ala-Gly-Acc-Aib-Pip-Gly-Leu-Iva-aX, a group of peptides with insecticidal activity isolated from the fungus Geotrichum candidum. AU 12 neoefrapeptins (A-I, L-N) contain the very rare amino acid 1-amino-cyclopropane-carboxylic acid (Acc), and some of them (F, I, L, M) also contain (2S,3S)-3-methyl-proline instead of pipecolic acid (Pip) in position 11. Further unusual building blocks are isovaline (Iva) and the C-terminal amide moiety X = 2,3,4,6,7,8-hexahydro-l-pyrrolo [ 1,2-a]pyrimidine. Neoefrapeptins show a close sequence similarity to the efrapeptins [A. Fredenhagen et al., J. Antibiot. 2006, 59, 2006]. 

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