Pyrrolo pyrimidine, preparation

Chlorouracil, in its protected form, can be formally viewed as a precursor in pyrrolo[2,3-rf pyrimidine preparations. Thus 135 is treated with 136, which presumably gives a 6-amino intermediate by displacing the chloro group, and subsequently cyclizes to 137 (Scheme 13) <1995JOC5069>. 

The pyrrolo[2,3-c/]pyrimidine anticancer agent is prepared utilizing, as a key sequence, Michael condensation of 2,6-diamino-4(.37/)-pyrimidinone with nitroalkenes, followed by the Nef reaction that leads to the annulated pyrrole ring (Eq. 10.67).98... 

Some interesting fused 1,2,3-triazole ring systems have been reported. A series of 5-piperidyl-substituted 7-hydroxy-3f/-l,2,3-triazolo[4,5-d]pyrimidines 143 has been synthesized from pipecolinate esters, benzylazides, and cyanoacetamide <06CHE246>. 4-Alkylidene-5,6-dihydro-4//-pyrrolo-[l,2-c][l,2,3]triazoles 144 were prepared from alkylidenecyclopropanes via diiodogenation/Cu(I)-catalyzed 1,3-dipolar cycloaddition/intra-molecular Heck reaction sequence <06SL1446>. 6,6-Dimethyl-2-phenyl-4,5,6,7-tetrahydro-27/-benzotriazol-4-one 145 were prepared from A-(5,5-dimethyl-3-oxocyclohexenyl)-S,S-diphenylsulfilimine and... 

Table 1 Preparation of unsaturated pyrrolo[1,2-c]pyrimidine (Scheme 29)...

A derivative of the related pyrrolo[l,2-a]pyrimidine system 84 was prepared from L-asparagine via a hydroxypyrrolidine (92JOC2641). 

Photochromic pyrrolo[2,3-d]pyrimidines 262-267 were prepared in 40-80% yields from thenoine 213 with substituted aminopyrimidines on heating in formic acid for 1-2 h (06MI2) (Scheme 73). 

The nature of aromatic enamines has no substantial effect on the pathway thus, pyrrolo[2,3-d]pyrimidines 265-267 were synthesized in comparable yields under the same conditions using thenoine 213 with fused aminopyrimidines (06MI2). Also new pyrrolo[2,3-d]pyridazines were prepared by the condensation of thenoine 213 with substituted 5-aminopyr-idazines 268 in formic acid followed by alkylation. Spectroscopic studies of 269 and 270 (Scheme 74) were reported. 

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. 

In an analogous fashion, pyrrolo[l,2-c]pyrimidine (66), the preparation of which was discussed in Section 6.2.2.1, was converted to the corresponding quatemized salt 67 <99JOC7788>. This heterocycle was shown to undergo 1,3-dipolar additions with a variety of dipolarophiles such as aUcynes to produce 68 after oxidation with DDQ. 

Another example of the simultaneous formation of both the pyrrolo and furo compounds has been observed. Nearly identical yields of 102c and 103b were isolated <2005JME5329>. Nonetheless, other 6-substituted derivatives of pyrrolo[2,3- pyrimidines have been prepared without complication, for example, 102d <2001JHC349> and a variety of arylmethyl compounds, illustrated by 102e <2003BMC5155>. 

Cyclization of 6-acetylenic derivatives constitutes yet another approach to pyrrolo[3,2-.7 pyrimidines. A series of 6-substituted acetylenes 209, prepared by alkynylation of the chloropyrimidine, undergo cyclization to the A -oxides 210 when heated briefly in pyridine (Equation 72) <2003SL1151, 2004CHE1335>. 

Several 7/7-pyrrolo[2,3-,y pyrimidin-2(77)-ones, via domino cross-coupling and cyclization reactions, were prepared from A -benzoyl-S-iodo-cytosine <2006H1325>. 

In addition to the substituted pyrrolo[2,3-d]pyrimidines discussed above, several 4-substituted-7-(8-D-ribofuranosyl)pyrrolo-[2,3-d]pyrimidines were also prepared and tested in the tobacco bioassay (85,86) most of the analogs inhibited the growth of tobacco callus cultured on kinetin. It is not clear from the published data, however, to what extent inhibition could be reversed by higher concentrations of kinetin. In addition, the analog... 

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