Pd/PTABS: Catalyst for Room Temperature Amination of Heteroarenes

Abstract

A mild and highly efficient catalytic amination procedure for chloroheteroarenes at ambient temperature using the Pd/PTABS catalytic system is reported. The protocol is selective for the amination of chloroheteroarenes using secondary amines such as piperidine, pyrrolidine, and several others. The exceptional mildness of the developed protocol is beneficial for the synthesis of a crucial Buparlisib intermediate as well as the formal synthesis of Alogliptin in competitive yields.

Pd/PTABS: An Efficient Water‐Soluble Catalytic System for the Amination of 6‐Chloropurine Ribonucleoside and Synthesis of Alogliptin

“…tert- 43 (s, 9H), 4H),1H),1H),3.96 q,J=3.40 Hz,1H),4H),1H),5.18 (d,J=4.91 Hz,1H),5.30 (dd,J=6.80,4.53 Hz,1H),5.45 (d,J=6.04 Hz,1H),5.93 (d,J=6.04 Hz,1H),8.27 (s,1H) C, 52.28; H, 6.47; N, 19.25%: found: C, 52.76: H, 6.44: N, 19.02%. Analytical data matches with that previously reported (Bandaru et al, 2018). [M+H].…”

“…[M+H]. Analytical data matches with that previously reported (Bandaru et al, 2018, Satishkumar et al, 2015. [M+H].…”

Discovery, Synthesis, and Scale-up of Efficient Palladium Catalysts Useful for the Modification of Nucleosides and Heteroarenes

“…Buparlisib is an important drug candidate exhibiting pan-PI3K inhibitor activity that is under clinical development, especially for brain tumor treatment [67]. This protocol also offered significant improvement in the yield over the previously reported methods for the amination of 6-chloropurine riboside providing 6-N-substituted adenosine analogues exhibiting promising applications in pharmacology and biochemistry (Scheme 13) [42]. This protocol also offered significant improvement in the yield over the previously reported methods for the amination of 6-chloropurine riboside providing 6-N-substituted adenosine analogues exhibiting promising applications in pharmacology and biochemistry (Scheme 13) [42].…”

“…Most of these protocols, however, suffer from several major drawbacks such as the high temperature of the reaction, longer reaction time, and low substrate scope of heteroarenes, which make the developed protocols synthetically less attractive [66]. These limitations were successfully addressed through the development of a room temperature amination protocol of chloroheteroarenes using the Pd/PTABS catalytic system (Scheme 12) [42]. Using the optimal reaction conditions for the amination of chloroheteroarenes, a wide range of heteroarenes were efficiently coupled with secondary amines.…”

“…Next, in order to have an efficient water-soluble catalytic system, we developed Pd-imidate based complexes in collaboration with the Serrano group, which were successfully utilized for Heck and Suzuki-Miyaura cross-coupling reactions [36][37][38]. Subsequently, we also developed triazaphosphaadamantane (PTA) based water-soluble phosphines, which are used in combination with palladium acetate for C-C and C-heteroatom bond forming reactions [39][40][41][42][43]. To minimize the duplication in structures, we will abbreviate the sugar units in forthcoming structures, as depicted in Figure 3.…”