One-Pot Synthesis of 5-Methyl-3H-pyrrolo[2,3-d]pyrimidin-4(7H)-one

Abstract

An efficient and environmentally benign synthesis of 5-methyl-3H-pyrrolo[2,3-d]pyrimidin-4(7H)-one is described. An acylprotected aminoacetone is reacted with cyanoacetamide to give 2-amino-4-methyl-1H-pyrrole-3-carboxamide, which is converted in one-pot to 5-methyl-3H-pyrrolo[2,3-d]pyrimidin-4(7H)-one in 60% overall yield. This process avoids the use of large excess Raney nickel which is required when known methods are practiced.

Synthesis of Heterospirocycles through Gold‐(I) Catalysis: Useful Building Blocks for Medicinal Chemistry

“…As our ultimate goal was to design biologically active spirocyclic molecules, the aza-spirocycle was then integrated into one of our on-going medicinal chemistry research projects for kinase inhibition. The hydrochloride salt 48 was reacted with the aromatic chloride 51 [14] to give the 4-amino pyrrolopyrimidine 52 in a 95% optimized yield (Scheme 6). Reductive removal of the tosyl group was then possible in the presence of sodium/naphthalene salt, to give the free amine 53 in 52% yield.…”

Evaluation of Sponge Metal Catalysts in a Trickle Bed Reactor for the Continuous Hydrogenation of an Aliphatic Nitro Intermediate

“…Sponge metals such as Raney nickel are commonly used in early-phase API clinical supply routes but are then worked out of later-stage development campaigns because of the perceived handling difficulties of these catalysts. − Placing the catalyst in a packed bed reactor and running the reaction continuously reduces potential exposure to the metal catalysts, avoids a hazardous filtration step, and allows for easier recycling of spent catalysts . Bayer recently demonstrated the use of a Raney cobalt catalyst in a fixed bed for the continuous reduction of an aromatic nitro group in a refametinib intermediate. , Hellgardt et al reported a two-stage continuous process using both Raney copper and Raney nickel for the hydrogenation of 5-(hydroxymethyl)­furfual …”