Synthesis of 6,7,8,9-tetrahydro-5H-pyrimido-[4,5-b][1,4]diazepine-6,8-diones
1993
The sodium ethoxide catalyzed condensation of 4,5-diaminopyrimidine (3) with diethyl malonate afforded 6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepine-6,8-dione (4). Methylation of 6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepine-6,8-dione (4) using sodium hydride and two equivalents of iodomethane gave 5,9-dimethyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepine-6,8-dione (5) which on further methylation using sodium hydride and one equivalent iodomethane yielded 6,7,8,9-tetrahydro-5,7,9-trimethyl-5H-pyrimido[4,5-b][1,4]diazepine-6,8-dione (6). Reaction of 6,7,8,9-tetrahydro-5H-pyrirnido[4,5-b][1,4]diazepine-6,8-dione (4) with 4.2 equivalents of sodium hydride and 4.1 equivalents of iodomethane afforded 6,7,8,9-tetrahydro-5,7,7, 9-tetramethyl-5H-pyrimido[4,5-b][1,4]diazepine-6,8-dione (7). 6,7,8,9-Tetrahydro-5,7,7,9-tetramethyl-5H-pyrimido[4,5-b][1,4]diazepine-6,8-dione (7) exhibited weak anticonvulsant activities in the subcutaneous pentylenetetrazole and maximal electroshock anticonvulsant screens indicating it is a partial bioisostere of the anticonvulsant drug clobazam (2).
Keywords:
- Correction
- Source
- Cite
- Save
- Machine Reading By IdeaReader
6
References
4
Citations
NaN
KQI