Ammonia methanol → Dimethylguanidine

Participants

Reaction Steps

Two 6,7-dihydropyrrolo[3,4-c]pyrido[2,3-d]pyrimidines which contain a novel tricyclic ring system of potential bilogical interest were sythesized. 6-(2,5-Dimethoxphenyl)-6,7-dihydropyrrolo[3,4-c]pyrido[2,3-d]pyrido[2,3-d]pyridmidine-2,4(1H,3H)-dione (3a) [throughout the Experimental Detail section, numbers in parenthesis () refer to numbered compounds in FIGS. 1 to 4] was prepared from a pyrido[2,3-d]pyrimidine. 6-Acetoxymethyl-5-methylpyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (4) was oxidized with SeO3 to the corresponding 5-formyl derivative (5) which was condensed with 2,5-dimethoxyaniline to form the Schiff base. Reduction of the exocyclic azomethine double bond of the Schiff base with NaBH3CN to (6) followed by thermal cyclization afforded (3a). 2,4-Diamino-6-(4-methoxyphenyl)-6,7-dihydropyrrolo[3,4-c]pyrido[2,3-d]pyrimidine (3b) was synthesized by addition of a pyrimidine ring to the dihydropyrrolo[3,4-c]pyridine system. 1-(4-Methoxphenyl)pyrrolidine- 3-one (18) was condensed with malononitrile to give a Knoevenagel adduct (19). Treatment of (19) with N,N-dimethylaminomethylene chloride in the presence of LDA afforded the 4-N,N-dimethylaminomethylenepyrrolidine derivative (20) which was converted into 6-amino-7-cyano-2,3-dihydropyrrolo[3,4-c]pyridine (21) by treatment with NH3 /MeOH. Cyclization of (21) with N,N-dimethyl-guanidine afforded the desired product (3b) in high yield.

Provenance & Evidence