The Synthesis of Pyrrolo[1,2-c]pyrimidine (6-Azapyrrocoline)¹

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

“…The only synthesis of pyrrolo[1,2- c ]pyrimidine that appears in the literature was reported by Rapoport et al . starting from 4-methylpyrimidine . After a sequence of seven steps, which included initial condensation with butyl glyoxalate, synthesis of 3-(4-pyrimidyl)-1-propanol 6 from the condensation product (three steps), formation of the 6,7-dihydro-5 H -pyrrolo[1,2- c ]pyrimidinium salt 7 , and final oxidation, the overall yield obtained was less than 1%, mainly because the last step produced a yield of 9% (Scheme ).…”

“…Pyrrolo[1,2- c ]pyrimidine (1a) was prepared according to standard procedures in a 51% yield: mp 42−44 °C (from hexanes−EtOH) (lit . mp 37−39 °C); IR (KBr) 1612, 1232 cm -1 ; 1 H NMR (300 MHz, CDCl 3 ) δ 8.76 (s, 1H), 7.36 (d, 1H, J = 6.5 Hz), 7.34 (dd, 1H, J = 2.9, 1.5 Hz), 7.21 (dd, 1H, J = 6.5,1.5 Hz), 6.87 (dd, 1H, J = 4.0, 2.9 Hz), 6.43 (dd, 1H, J = 4.0, 1.5 Hz); 13 C NMR (75 MHz, CDCl 3 ) δ 138.5, 136.1, 130.9, 115.8, 113.1, 110.3, 99.3; MS m / z (rel int) 118 (M + , 100), 91 (26), 80 (28).…”

Reaction of Bromomethylazoles and Tosylmethyl Isocyanide. A Novel Heterocyclization Method for the Synthesis of the Core of Marine Alkaloids Variolins and Related Azolopyrimidines

“…We previously reported a novel synthesis of pyrrolo[1,2- c ]pyrimidine and some derivatives based on the reaction of tosylmethyl isocyanide (TosMIC) with 2-pyrrole carboxaldehydes . This method provided a simple and efficient route to the target system, which could be obtained in 40% overall yield (compared to 1% for the previously reported procedure).…”

Pyrrolodiazines. 2. Structure and Chemistry of Pyrrolo[1,2-a]pyrazine and 1,3-Dipolar Cycloaddition of Its Azomethine Ylides

“…This is probably because of difficulties associated with their preparation, with the four possible pyrrolodiazine isomers 1 − 4 all being prepared by synthetic routes which are both lengthy and poor yielding. The syntheses of the pyrrolo[1,2- a ]pyrimidine 2 , the pyrrolo[1,2- c ]pyrimidine 3 , and the pyrrolo[1,2- b ]pyridazine 4 are reported in an overall yield of less than 5% while the pyrrolo[1,2- a ]pyrazine 1 system was prepared in a total yield of 18%. Moreover, only one of the six possible dihydro derivatives, the 3,4-dihydropyrrolo[1,2- a ]pyrazine 5 is known, and its synthesis has also been reported in low yield.…”