Patent FR-2829404-A1 (FR)
Title: Modular automatic apparatus for synthesizing small organic molecules, particularly in the solid phase, using combining or parallel synthesis protocols
Inventor: NEIMARK JEAN
IPC: C40B40/10
Filed: 2001-09-10
Abstract: Modular automatic apparatus, where a number of synthesis modules (2) each contain between 3 and 10, preferably 5 reactors (3), with one secondary mixing chamber (6) per module and a principal mixing chamber (7) for all the modules, is new. A single computer controls the flow through the circuits connecting these reactors and chambers, the means of heating and cooling the reactors and the means of mixing in the reactors. Modular automatic apparatus, where a number of synthesis modules (2) each contain between 3 and 10, preferably 5 reactors (3), with one secondary mixing chamber (6) per module and a principal mixing chamber (7) for all the modules, is new. A single computer controls the flow through the circuits connecting these reactors and chambers, the means of heating and cooling the reactors and the means of mixing in the reactors. Each reactor has a tubular body with an upper injection and expansion plug and a lower fixed plug for controlled extraction and emptying. This contains a reaction chamber which is normally sealed closed and is temperature controlled by means of heating and cooling. The reaction chamber contains means of agitating the reaction medium by bubbling and/or using a mechanical device. A container (6) forms a secondary mixing chamber which can contain the same amount as all the reactors in a module and a supplementary container (7) forms the principal mixing chamber which can contain the same amount as all the different secondary mixing chambers. A circuit transfers the contents of the reactors to the secondary container associated with that module and/or the contents of the principal container to the secondary container or the reactors of one, several or all of the modules in the apparatus. Supply and evacuation circuits are connected to the different inlets and outlets of the reactors and containers to allow fluid circulation under the action of an inert or neutral propulsion gas. These are formed of interconnected pipes or sections of pipe linking the reactors and containers to each other and to solution reservoirs (9, 10, 11, 12) and expansion, supply and gas injection or bubbling lines via one-way or multiway (16, 17) valves and monoblocs with programmable nodes to configure the circuit and control distribution of the fluids in the circuit. In particular, a single computer is connected to electronic interface and multiplexing circuits to control the valves, the means of heating and cooling and the means of agitating the contents of the reaction chambers, integrating the interfaces to communicate and be programmed by the operator. The apparatus contains three sub-units, one with five reactors and the other two with two modules of five reactors each. The reactors in each module are arranged to be at equal angles or equidistant arranged around a circle and mounted in a support structure containing the multi-way valves which control access to the reaction chambers. The fixed lower plug holds a filter and a drain. Each module is insulated thermally from the others. The means of heating and cooling are coils around each reactor. The principal and secondary containers are tubes containing several injection pipes for different solvents and substances for the synthesis. Intermediate synthesis products are mixed with their solid synthesis support in each reactor using a transfer and division process. In particular, the transfer solution carrying synthesis products in suspension is DCM (dichloromethane) or DMF (dimethylformamide). An Independent claim is also included for a process of synthesizing organic molecules using a combinatory synthesis protocol in the solid phase using the novel apparatus.