Chemistry of the pyrrolo[3,4-c]pyrido[2,3-d]pyrimidine system. Synthesis of 6,7-dihydropyrrolo[3,4-c]pyrido[2,3-d]pyrimidines, a novel ring system with potential biological interest Journal Article
| Authors: | Su, T. L.; Watanabe, K. A. |
| Article Title: | Chemistry of the pyrrolo[3,4-c]pyrido[2,3-d]pyrimidine system. Synthesis of 6,7-dihydropyrrolo[3,4-c]pyrido[2,3-d]pyrimidines, a novel ring system with potential biological interest |
| Abstract: | Two 6,7-dihydropyrrolo[3,4-c]pyrido[2,3-d]pyrimidines, which contain a novel tricyclic ring system of potential biological interest, were synthesized. 6-(2,5-Dimethoxyphenyl)-6,7-dihydropyrrolo[3,4-c]pyrido[2,3-d]pyrimidine-24(lH,3H)-dione (3a) was prepared from a pyrido[2,3-d]pyrimidine. 6-(Acetoxymethyl)-5-methylpyrido-[2,3-d]pyrimidine-2,4(lH,3H)-dione (4) was oxidized with SeO2 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. l-(4-Methoxyphenyl)pyrrolidin-3-one (18) was condensed with malononitrile to give a Knoevenagel adduct 19. Treatment of 19 with (N,N-dimethylamino)methylene chloride in the presence of LDA afforded the 4-[(N,N-dimethylamino)methylene]pyrrolidine 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-dimethylguanidine afforded the desired 3b in high yield. © 1989, American Chemical Society. All rights reserved. |
| Keywords: | unclassified drug; nonhuman; drug synthesis; nuclear magnetic resonance; pyrrolo[3',4':3,4]pyrido[2,3 d]pyrimidine derivative |
| Journal Title: | Journal of Organic Chemistry |
| Volume: | 54 |
| Issue: | 1 |
| ISSN: | 0022-3263 |
| Publisher: | American Chemical Society |
| Date Published: | 1989-01-01 |
| Start Page: | 220 |
| End Page: | 224 |
| Language: | English |
| DOI: | 10.1021/jo00262a046 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 14 April 2020 -- Source: Scopus |
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