One-step synthesis of heteroaromatic-fused pyrrolidines via cyclopropane ring-opening reaction: application to the PKCbeta inhibitor JTT-010.
A ring-opening reaction of cyclopropanes with five-membered heteroaromatics having a leaving group at C(2) was found to provide heteroaromatic-fused pyrrolidines in one step. This reaction was successfully applied to the synthesis of the protein kinase C-beta inhibitor JTT-010, which possesses a dihydropyrrolo[1,2-a]indole core.
Tanaka
Masahiro
M
Central Pharmaceutical Research Institute, Japan Tobacco Inc., Takatsuki Osaka 569-1125, Japan.
Ubukata
Minoru
M
Matsuo
Takafumi
T
Yasue
Katsutaka
K
Matsumoto
Katsuya
K
Kajimoto
Yasuyuki
Y
Ogo
Takashi
T
Inaba
Takashi
T
D003521:Cyclopropanes / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis; D006571:Heterocyclic Compounds / Q000138:chemical synthesis; D007189:Indans / Q000138:chemical synthesis; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D064546:Protein Kinase C beta; D011758:Pyrroles / Q000138:chemical synthesis; D011759:Pyrrolidines / Q000138:chemical synthesis*
C508122:(2R)-3-(2-aminomethyl-2,3-dihydro-1H-3a-azacyclopenta(a)inden-8-yl)-4-phenylaminopyrrole-2,5-dione monomethanesulphonate; D003521:Cyclopropanes; D004791:Enzyme Inhibitors; D006571:Heterocyclic Compounds; D007189:Indans; D011758:Pyrroles; D011759:Pyrrolidines; C030797:cyclopropane; D011493:Protein Kinase C; D064546:Protein Kinase C beta