Synthesis of Dolutegravir Exploiting Continuous Flow Chemistry

Contributor(s):: Nqeketo, Sinazo, Watts, Paul

An efficient continuous flow process for the synthesis of dolutegravir, an active pharmaceutical ingredient (API) for HIV treatment, was investigated. The synthetic procedure starts from a readily available benzyl-protected pyran via six chemical transformations using continuous flow reactors....

Synthesis of treprostinil: key Claisen rearrangement and catalytic Pauson–Khand reactions in continuous flow

Contributor(s):: García-Lacuna, Jorge, Domínguez, Gema, Blanco-Urgoiti, Jaime, Pérez-Castells, Javier

A new synthesis of treprostinil is described using a plug flow reactor in two of the key steps. First, a Claisen rearrangement reaction is described in scaled flow at multigram amounts. Yields and selectivity of this step are sharply improved compared to those from previous syntheses. Second, the...

The Application of a Continuous Grignard Reaction in the Preparation of Fluconazole

Contributor(s):: Korwar, Sudha, Amir, Somi, Tosso, Perrer N., Desai, Bimbisar K., Kong, Caleb J., Fadnis, Swara, Telang, Nakul S., Ahmad, Saeed, Roper, Thomas D., Gupton, B. Frank

The application of continuous methods in the synthesis of active pharmaceutical ingredients continues to receive significant attention in the academic as well as the industrial research communities. One of the major advantages of continuous methods is the ability to safely access kinetic synthons...

Use of a “Catalytic” Cosolvent, N,N-Dimethyl Octanamide, Allows the Flow Synthesis of Imatinib with no Solvent Switch

Contributor(s):: Yang, Jeffrey C., Niu, Dawen, Karsten, Bram P., Lima, Fabio, Buchwald, Stephen L.

A general, efficient method for C−N cross-coupling has been developed using N,N-dimethyloctanamide as a catalytic cosolvent for biphasic continuous-flow applications. The described method was used to generate a variety of biarylamines and was integrated into a two-step sequence which converted...

Use of High-Throughput Tools for Telescoped Continuous Flow Synthesis of an Alkynylnaphthyridine Anticancer Agent, HSN608

Contributor(s):: Biyani, Shruti A., Qi, Qingqing, Wu, Jingze, Moriuchi, Yuta, Larocque, Elizabeth A., Sintim, Herman O., Thompson, David H.

Developing continuous syntheses of lead compounds to support in vivo studies and preclinical evaluation remains an underdeveloped area. We report a telescoped continuous flow synthesis of an alkynylnaphthyridine lead compound for the treatment of FLT3 mutations in acute myeloid leukemia....