Pyrrolodiazines. 5. Synthesis, Structure, and Chemistry of Pyrrolo[1,2-c]pyrimidine. Dipolar Cycloaddition of Pyrrolo[1,2-c]pyrimidinium Ylides

Abstract

An improved synthesis of pyrrolo[1,2-c]pyrimidines, including the parent system, was accomplished via sequential condensation of substituted pyrrole-2-carboxaldehydes with tosylmethyl isocyanide (TOSMIC), followed by desulfonylation of the formed tosylpyrrolo[1,2-c]pyrimidines. Based on the ab initio calculations performed on the pyrrolo[1,2-c]pyrimidine 1a, some of the basic chemistry was investigated, including electrophilic substitution, addition of organolithium reagents, metalation with lithium diisopropylamide (LDA) and subsequent reaction with electrophiles, and formation of salts by quaternization of the nonbridgehead nitrogen. Azomethine ylides generated from pyrrolo[1,2-c]pyrimidinium salts undergo 1,3-dipolar cycloaddition with suitable dipolarophiles to give new dipyrrolo[1,2-a;1‘,2‘-c]pyrimidine derivatives, with high regio- and stereoselectivity.

Discovery, Structure–Activity Relationship, and Antiparkinsonian Effect of a Potent and Brain-Penetrant Chemical Series of Positive Allosteric Modulators of Metabotropic Glutamate Receptor 4

“…The title compound was prepared in a manner analogous to 11 (43%, overall yield), starting from pyrrolo­[1,2- c ]­pyrimidine-3-carboxylic acid methyl ester …”

“…The title compound was prepared in a manner analogous to 11 (43%, overall yield), starting from pyrrolo[1,2-c]pyrimidine-3-carboxylic acid methyl ester. 40 1 H NMR (300 MHz, DMSO-d 6 ) δ 10.97 (s, 1H), 9.22 (s, 1H), 8.05 (s, 1H), 7.88 (dd, J = 7.9, 2.4 Hz, 1H), 7.82 (d, J = 2.4 Hz, 1H), 7.54−7.42 (m, 2H), 7.46 (s, 1H), 7.27 (t, J = 6.8 Hz, 1H), 6.97 (dd, J = 3.7, 2.9 Hz, 1H), 6.74 (d, J = 3.7 Hz, 1H). 13 2-Thieno[2,3-c]pyridin-5-yl-chromen-4-one Oxime (15).…”

2-Azaallyl Anions, 2-Azaallyl Cations, 2-Azaallyl Radicals, and Azomethine Ylides

“…The most direct method for the formation of N -alkyl azomethine ylides ( 290 ) is the deprotonation of the corresponding iminium 293 (Scheme ) using an appropriate base (which could be the water generated upon iminium condensation). − Treatment of N -oxides with LDA also was proposed to generate azomethine ylide intermediates (Scheme ). While direct deprotonation of imines 294 (R 1 = H) typically affords a 2-azaallyl anion, the corresponding N-protonated azomethine ylides ( 289 ) can be accessed via a 1,2-prototropic rearrangement of imines 294 , as was pioneered by Grigg − and utilized by many others (Scheme ).…”

Utilities of Some Carbon Nucleophiles in Heterocyclic Synthesis

“…In an effort to explore the chemistry of pyrrolodiazines and their quaternized salts, Alvarez-Builla and co-workers [247] prepared a series of pyrrolo [1,2-c]pyrimidines via methodology developed in their laboratory. Similarly, isoquinoline-1-ylacetonitrile 415 reacts with 416a-c to give 422a-c, as outlined in Scheme 137.…”