Across‐the‐World Automated Optimization and Continuous‐Flow Synthesis of Pharmaceutical Agents Operating Through a Cloud‐Based Server

Abstract

The power of the Cloud has been harnessed for pharmaceutical compound production with remote servers based in Tokyo, Japan being left to autonomously find optimal synthesis conditions for three active pharmaceutical ingredients (APIs) in laboratories in Cambridge, UK. A researcher located in Los Angeles, USA controlled the entire process via an internet connection. The constituent synthetic steps for Tramadol, Lidocaine, and Bupropion were thus optimized with minimal intervention from operators within hours, yielding conditions satisfying customizable evaluation functions for all examples.

The Fascinating Chemistry of α‐Haloamides

“…Replacement of the α‐halogen atom by nitrogen nucleophiles in the presence of inorganic or organic bases is among the available methods for the synthesis of α‐amino amides using α‐chloro, α‐bromo and α‐iodoamides as starting materials. Lidocaine (15.7 g) has been recently produced by Ley and co‐workers under flow conditions within two working days (85 % overall yield) . The second reaction of the two‐step synthesis consisted of the diethylamine alkylation with 2‐chloro‐ N ‐(2,6‐dimethylphenyl)acetamide in the presence of Et 3 N. Optimized conditions featured DMF as the solvent, a reactor temperature of 99 °C, residence time of 17.8 min, and 3.9 equiv.…”

A tutored discourse on microcontrollers, single board computers and their applications to monitor and control chemical reactions

“…14 Finally, in three further papers we describe particularly how web-based techniques operating devices through the internet 15 and the cloud can enhance autonomous self-optimization and integration with batch processing, 16 permitting remote control and access across the world, independently of time domains. 17 Later in this paper we describe in more detail how these selfoptimisation algorithms work and how they can be harnessed for a wide variety of applications.…”

“…Recently we reported an application of reaction control and self-optimisation which was spread across the world geographically. 17 The equipment on which reactions were conducted and analytical data collected were located in our laboratories in Cambridge, UK, while the control server directing all experimentation was based in Tokyo, Japan. An operator was able to initiate and monitor reaction progress for all examples from Los Angeles, USA.…”

“…8 Global networking through the internet was exploited to perform rapid self-optimisation experiments for three API targets, allowing an operator in the United States to control equipment in the United Kingdom through servers in Japan. 17…”

Toward “On‐Demand” Materials Synthesis and Scientific Discovery through Intelligent Robots

“…It needs an intelligent brain that well coupled neuron networks, physical‐chemistry theory and scientists‐machine interactions . Since yet, most of the algorithms‐assisted synthesis system was utilized for optimizing organic molecular reaction, for example, the SNOBFIT‐assisted robotic platform in Massachu‐setts Institute of Technology (MIT), and the cloud synthesis system based on Complex Method in Cambridge . For higher demand, brains of these self‐driving laboratories are expected to extract the common concepts in experimental science, having wider compatibility, and more expansion interface.…”