Practical Synthesis of 1-Substituted 5-Aminopyrazolo[4,3-d]pyrimidin-7-ones Using Intramolecular Friedel–Crafts Type Cyclization and Its Application to the Synthesis of Pharmaceutically Active Compounds

DMAPO/Boc2O‐Mediated One‐Pot Direct N1‐Acylation of Indazole with Carboxylic Acids: A Practical Synthesis of N1‐Functionalized Alkyl Indazoles

“…Finally, to demonstrate the potential usefulness of this stepwise but straightforward protocol for the selective synthesis of N 1‐functionalized alkyl indazoles, several control experiments were performed (Scheme 4B). For example, upon treatment of indazole with alcohol 55 under Mitsunobu reaction conditions, [17i,j,k] a complex mixture containing dehydrated byproduct 56 was produced, and the desired N ‐alkyl indazole 51 was not obtained at all. Similarly, under the conditions of N ‐alkylation by a classical nucleophilic substitution reaction of indazole [17d,j,k] with methanesulfonate 57 , a complex mixture containing dehydrated byproduct 56 was obtained, but no desired N ‐alkyl indazole 51 .…”

“…For example, upon treatment of indazole with alcohol 55 under Mitsunobu reaction conditions, [17i,j,k] a complex mixture containing dehydrated byproduct 56 was produced, and the desired N ‐alkyl indazole 51 was not obtained at all. Similarly, under the conditions of N ‐alkylation by a classical nucleophilic substitution reaction of indazole [17d,j,k] with methanesulfonate 57 , a complex mixture containing dehydrated byproduct 56 was obtained, but no desired N ‐alkyl indazole 51 . These results demonstrate that our newly developed protocol shown in Scheme 4A would be useful for the selective synthesis of N 1‐substituted alkyl indazoles.…”

Regioselective synthesis of N1-substituted-4-nitropyrazole-5-carboxylates via the cyclocondensation of ethyl 4-(dimethylamino)-3-nitro-2-oxobut-3-enoate with substituted hydrazines

“…N1-substitued-4-aminopyrazole-5-carboxylate fragments are important heterocyclic scaffolds in organic synthesis, especially in the preparation of biologically important and medicinally useful agents such as microtubule targeting agents, 1 DNA polymerase IIIC inhibitors, 2 mTOR inhibitors, 3 PDE2 and TNFα inhibitors, 4 Human TLR7 agonists, 5 HIF-PHD inhibitor, 6 TRPA1 modulators 7 and Adenosine receptor antagonists. 8 As the most notable example, 1-methyl-3-propyl-4-aminopyrazole-5-carboxylic amide constituted the key structural unit of the blockbuster drug Sildenafil citrate (the active ingredient in Viagra®), a phosphodiesterase (V) inhibitor (Fig.…”