Chemical processing platform

Abstract

The present invention provides a method of performing a synthetic procedure comprising a plurality of different synthetic operations on a chemical processing platform. The method uses synthetic procedures to generate instruction sets for executing synthetic operations on reaction mixtures and collects associated operation data which is used to generate, and adapt, further synthetic operations. Also provided is a chemical processing platform for performing a plurality of synthetic operations.

Description

[0001] CHEMICAL PROCESSING PLATFORM

[0002] Related Application

[0003] The present application claims priority to, and the benefit of, GB 2411832.5 filed on 9 August 2024 (09 / 08 / 2024), the contents of which are hereby incorporated by reference in their entirety.

[0004] Field of the Invention

[0005] The present invention relates to a method of performing a synthetic procedure comprising a plurality of synthetic operations on a chemical processing platform. Also provided is a chemical processing platform for performing a plurality of synthetic operations and a use of the chemical processing platform for performing a synthetic procedure.

[0006] Background

[0007] Methods and systems for performing automated chemical synthesis involve the performance of chemical reactions, synthesis and discovery of new compounds, and the optimisation of their reaction conditions, without direct involvement from a human user. Such methods and systems aim to improve the speed, precision, and reproducibility of chemical reactions, and reduce the need for an experienced chemist to operate synthetic procedures, which ultimately advances the capabilities of chemical research and development.

[0008] Chemical synthesis requires intensive, highly skilled labour and a typical laboratory-scale synthesis can require multiple complex synthetic operations that are difficult to explicitly encode. By using machine-readable instruction sets and physical reaction vessels developed from digital models that are responsive to the machine-readable instructions, it is possible to develop and utilise standardised models for chemical synthesis that can be executed by automated synthesisers. Such machine-readable instruction sets are most commonly adapted from chemical literature and follow a strict, predetermined synthetic operation.

[0009] For this reason, dynamic synthetic procedures, which may be required in the consideration of the reaction’s environmental conditions, changes in reagent source, and to make adjustments based on the progress of the reaction itself, are important in chemical synthesis. However, performing autonomous dynamic synthesis is challenging. A human user may be capable of performing dynamic steps based on their prior experience, but at the cost of intensive, highly skilled labour. To fully exploit the potential of automation in chemical synthesis and ensure reproducibility of procedures, progress is needed.

[0010] 008773897 The present inventor has previously shown how a method for generating a database for chemical syntheses may be used for automatic chemical synthesis: see WO 2024 / 003151. This method generates a series of instruction sets for a series of chemical syntheses from the literature. The series of instruction sets are assembled within a database and are made available for access and autonomous execution by a chemical synthesiser. The instruction set may be revised where a chemical synthesis is not satisfactory, so that a future chemical synthesis provides a satisfactory result.

[0011] However, while such methods focus on the execution of a single chemical synthesis route, they are limited to the complete conversion of a chemical synthesis in the literature from manual operation to a machine-readable instruction set. There are still challenges in providing laboratory-scale methods and systems which employ a dynamic adjustment and decision-making during the progression of a synthetic procedure. The lack of integration of dynamic adjustment also means that the aforementioned system cannot be verified and thus no error correction is possible.

[0012] Therefore, there is a need for the development of new methods and chemical processing platforms which address these problems.

[0013] Summary of the Invention

[0014] The present invention provides methods for performing chemical or biological synthesis, and focuses on the use of operation data to influence the particular synthetic operations to be performed. Typically, the methods of performing synthetic operations are for providing a route to a final reaction product. Typically, the chemical processing platform is an autonomous chemical processing platform, such that the synthetic operations are performed autonomously.

[0015] In particular, the methods of the present invention are for performing a series of synthetic operations on a reaction mixture, where the synthetic operation selected based on initial data which can be provided by a human user, collecting operation data from that synthetic operation, and selecting a further synthetic operation based on the operation data from that synthetic operation. That is, the method focuses on generating new operation data based on previous synthetic operations performed on reaction mixtures, and the new operation data directly guides the further synthetic operations. The invention provides error correction in real time to ensure reproducibility.

[0016] As such, the method also makes the extensive natural language chemical literature directly executable on a chemical processing platform. A chemist with no knowledge of programming can make use of synthetic operations to perform synthetic techniques based only on their knowledge of the synthetic procedures in the form of natural language.

[0017] Typically, a chemist need only provide the input data required for a target reaction product.

[0018] 008773897 In general, for a synthetic procedure, the method may comprise:

[0019] (i) generating an instruction set for a synthetic operation based on a synthetic procedure and the operation data from one or more previous synthetic operations;

[0020] (ii) executing the synthetic operation on a reaction mixture to obtain a reaction mixture;

[0021] (iii) collecting operation data about the synthetic operation performed on the reaction mixture;

[0022] (iv) repeating steps (i) to (iii) for the next synthetic operations in the synthetic procedure.

[0023] For example, for a synthetic procedure performed on chemical processing platform, the method may comprise:

[0024] (i) generating an instruction set for a synthetic operation based on a synthetic procedure and the operation data from one or more previous synthetic operations, using the control unit;

[0025] (ii) executing the synthetic operation on a reaction mixture to obtain a reaction mixture using a substation;

[0026] (iii) collecting operation data about the synthetic operation performed on the reaction mixture using the operation data collection unit;

[0027] (iv) repeating steps (i) to (iii) for the next synthetic operations in the synthetic procedure.

[0028] In general, for a synthetic procedure having ‘n’ synthetic operations, the method may comprise:

[0029] (i) generating an instruction set for a nthsynthetic operation based on a synthetic procedure and the n-1thoperation data;

[0030] (ii) executing the nthsynthetic operation on a nthreaction mixture to obtain a n+1threaction mixture;

[0031] (iii) collecting nthoperation data about the nthsynthetic operation performed on the nthreaction mixture;

[0032] (iv) repeating steps (i) to (iii) for the n synthetic operations in the synthetic procedure.

[0033] In general, for a synthetic procedure having ‘n’ synthetic operations performed on chemical processing platform, the method may comprise:

[0034] (i) generating an instruction set for a nthsynthetic operation based on a synthetic procedure and the n-1thoperation data using the control unit;

[0035] (ii) executing the nthsynthetic operation on a nthreaction mixture to obtain a n+1threaction mixture using a nthsubstation;

[0036] (iii) collecting nthoperation data about the nthsynthetic operation performed on the nthreaction mixture using the operation data collection unit;

[0037] (iv) repeating steps (i) to (iii) for the n synthetic operations in the synthetic procedure.

[0038] 008773897 In a general aspect, there is provided a method of performing a synthetic procedure, wherein the synthetic procedure comprises a plurality of different synthetic operations, the method comprising the steps of:

[0039] (a) generating an instruction set for a first synthetic operation based on a synthetic procedure;

[0040] (b) executing the first synthetic operation on a reaction mixture;

[0041] (c) collecting operation data about the synthetic operation performed;

[0042] (d) generating an instruction set for a second synthetic operation based on the synthetic procedure and the operation data; and

[0043] (e) executing the second synthetic operation.

[0044] The method is typically performed on a chemical processing platform. The chemical processing platform typically comprises a network of two or more stations, wherein each station comprises one or more substations, an operation data collection unit and a control unit.

[0045] In this way, a subsequent step in the synthetic procedure has its instruction set adapted based on operation data from one or more earlier synthetic operations. The method of the invention can make adjustments to the immediate synthetic operations within the overall chemical synthesis based on information about the operation of previous synthetic operations. This allows the method and processing platform to account for changes in environmental conditions, the nature of the reaction progress, the source of the reagents used, and other variables not considered within the confines of a purely literature derived instruction set. It follows that the method and platform of the invention can carry out synthetic procedures with excellent reproducibility, autonomy and final product quality.

[0046] Advantageously, the chemical processing platform may be used to improve the efficiency of synthetic procedures. For example, the chemical processing platform provides a route to the optimisation of a particular reaction, such as the yield of a specific target reaction product.

[0047] Accordingly, in a first aspect of the invention, there is provided a method of performing a synthetic procedure on a chemical processing platform, wherein the synthetic procedure comprises a plurality of different synthetic operations, the chemical processing platform comprising a network of two or more stations, wherein each station comprises one or more substations, an operation data collection unit and a control unit; and the method comprising:

[0048] (a) generating an instruction set for a first synthetic operation based on a synthetic procedure using the control unit;

[0049] 008773897 (b) executing the first synthetic operation on a first reaction mixture to obtain a second reaction mixture using a first substation;

[0050] (c) collecting first operation data about the first synthetic operation performed on the first reaction mixture using the operation data collection unit;

[0051] (d) generating an instruction set for a second synthetic operation based on the synthetic procedure and the first operation data using the control unit; and

[0052] (e) executing the second synthetic operation on the second reaction mixture to obtain a third reaction mixture using a second substation.

[0053] In some embodiments, the synthetic operation is performed autonomously by the chemical processing platform, such as a substation, according to the instruction set. This may be referred to as an automated synthetic operation.

[0054] Accordingly, there is also provided a method of autonomously performing a synthetic procedure on a chemical processing platform, wherein the synthetic procedure comprises a plurality of different synthetic operations, the chemical processing platform comprising a network of two or more stations, wherein each station comprises one or more substations, an operation data collection unit and a control unit; and the method comprising:

[0055] (a) generating a machine-readable instruction set for a first automated synthetic operation based on a synthetic procedure using the control unit;

[0056] (b) executing the first automated synthetic operation on a first reaction mixture to obtain a second reaction mixture using a first substation;

[0057] (c) collecting first operation data about the first automated synthetic operation performed on the first reaction mixture using the operation data collection unit;

[0058] (d) generating a machine-readable instruction set for a second automated synthetic operation based on the synthetic procedure and the first operation data using the control unit; and

[0059] (e) executing the second automated synthetic operation on the second reaction mixture to obtain a third reaction mixture using a second substation.

[0060] The synthetic procedure may be manually provided by a human user. The synthetic procedure may be in a natural language, such as in prose. The synthetic procedure may be encrypted. The synthetic procedure may be encrypted in natural language, such as encrypted prose.

[0061] The synthetic procedure is coordinated by a control unit within the chemical processing platform. The control unit may generate instruction sets for a user, e.g., a human user. In this way, the user may execute the synthetic operation on the substations. Preferably, the

[0062] 008773897 control unit generate machine readable instruction sets for the two or more stations. In this way, the substation may execute the synthetic operation autonomously.

[0063] The instruction set may be a machine-readable instruction set. The instruction set may be in a mark-up language, such as a descriptive mark-up language. Any suitable mark-up language may be used, for example XML, XDL, and / or YAML. Preferably, the instruction set is in XDL. In particular, YAML may allow for compact representations that can embed logical arguments, and is compatible with XML or XDL. The instruction set may be encrypted. The instruction set may be encrypted in mark-up language, such as encrypted XML, XDL, and / or YAML.

[0064] The synthetic operation may be performed on the chemical processing platform, according to the instruction set. This may be referred to as a manual synthetic operation. The synthetic operation may be performed manually, such as by a human user. The synthetic operation may be performed manually on the chemical processing platform, such as on the substation.

[0065] The synthetic operation is performed on a reaction mixture, which may contain reagents for a chemical reaction, or a crude reaction product for purification or analysis.

[0066] The operation data is collected by the operation data collection unit in the chemical processing platform, and the operation data is used to generate a further instruction set for a further synthetic operation, such as a second synthetic operation, by the control unit.

[0067] Between executing the first synthetic operation and executing the second synthetic operation, the second reaction mixture may be transferred autonomously by the chemical processing platform, or manually by a human user.

[0068] Therefore, the method generally involves generating instruction sets, such as from synthetic procedure in natural language, and each instruction set is for executing a synthetic operation. The instruction set is typically a machine-readable instruction set Importantly, the execution of an instruction set is associated with the collection of operation data, and this operation data is used to inform further synthetic operations by dynamically altering and adapting the associated instruction set, together with the existing synthetic procedure.

[0069] The step of generating an instruction set for a second synthetic operation may be based on the synthetic procedure and the operation data available for each synthetic operation in the synthetic procedure.

[0070] In some embodiments, wherein the chemical processing platform is an autonomous chemical processing platform, such that each of step (a) to step (e) is performed autonomously.

[0071] 008773897 Collecting first operation data may occur concurrently with executing the first synthetic operation on a first reaction mixture to obtain a second reaction mixture.

[0072] The method may further comprise a step (f) of comparing the operation data to reference operation data. Comparison of the operation data to reference operation data allows the synthetic operations to be validated. Thus, the method may comprise a step (f) of comparing the operation data to reference operation data, and validating the synthetic operation based on the comparison.

[0073] Comparison of the operation data to reference operation data allows the synthetic operations to be corrected, if the synthetic operation fails the validation. Thus, the method may comprise a step (f) of comparing the operation data to reference operation data, validating the synthetic operation based on the comparison, and updating the instruction set based on the comparison. The instructions set may be updated during execution of a synthetic operation.

[0074] The reference operation data is typically operation data for a reference synthetic operation. The synthetic operation and the reference synthetic operation typically have the same reaction mixture and conditions. The synthetic operation and the reference synthetic operation may have the same instruction set.

[0075] The method may further comprise a step (f) of comparing the operation data to aggregated reference operation data. The aggregation of operation data is as described herein. The aggregated operation data is typically operation data for a reference synthetic operation. The aggregated operation data may be operation data for a reference synthetic procedure. The synthetic procedure may comprise a plurality of synthetic operations. Thus, the aggregated operation data may be aggregated from a plurality of synthetic operations of a reference synthetic procedure. The synthetic procedure and the reference synthetic procedure typically have the same reaction mixture and conditions. The synthetic procedure and the reference synthetic procedure may have the same instruction sets.

[0076] The present invention is also particularly concerned with methods of optimising the performance of performing a plurality of synthetic operations using the chemical processing platform. The methods of optimising the performing of performing synthetic operations are typically for improving the efficiency and the reproducibility of future plurality of synthetic operations based on an existing plurality of synthetic operations.

[0077] The method also seeks to produce a library of operation data, which may be useful for exploring the chemical space, and adapting, altering and modifying future synthetic procedures for a particular chemical reaction. The method may also be used for optimising the efficiency and reproducibility of a particular chemical reaction by optimising the reaction

[0078] 008773897 conditions, based on operation data collected for and during a concurrent run through a plurality of synthetic operations. In particular, the library of operation data may be useful for optimising a chemical reaction, such as the conditions for each specific synthetic operation, based on the operation data collected from previous runs on the chemical processing platform.

[0079] Thus, by performing a plurality of synthetic operations on a reaction mixture, the method allows for the build-up of an aggregation of operation data by collecting operation data for each synthetic operation. This data can be used for validation and error correction, as described above.

[0080] The present inventors have shown that by performing a plurality of synthetic operations on a reaction mixture, such that operation data is collected from each synthetic operation at each stage in the synthesis, the aggregation of operation data at the end of the performance may be stored and used to inform a future plurality of synthetic operations.

[0081] In another aspect of the invention, there is provided a chemical processing platform for performing a synthetic procedure. The chemical processing platform may be used in the method of the first aspect. The chemical processing platform may be used for chemical and biological synthesis, for example for the synthesis, discovery, analysis and data acquisition of new chemical and biological entities.

[0082] In a second aspect of the invention there is provided a chemical processing platform for performing a synthetic procedure, wherein the synthetic procedure comprises a plurality of synthetic operations, the chemical processing platform comprising: a network of two or more stations, optionally three or more stations, wherein each station is in direct and / or indirect material intercommunication with each of the other stations, and each station comprises one or more substations, wherein each substation in a first station is for executing a different synthetic operation to each substation in a second station; and an operation data collection unit for collecting operation data on the synthetic operation performed within the substations; and a control unit in signalling communication with the two or more stations and the operation data collection unit, wherein the control unit is for receiving operation data from the operation data collection unit, generating an instruction set based on the synthetic procedure and the operation data, and providing the substation with the instruction set for execution of the synthetic operation.

[0083] In some embodiments, the chemical processing platform is autonomous. In some embodiments one or more stations or substations are autonomous. That is, the station or substations is able to execute an automated synthetic procedure according to a machine- readable instruction set.

[0084] 008773897 Accordingly, there is also provided a chemical processing platform for autonomously performing a synthetic procedure, wherein the synthetic procedure comprises a plurality of automated synthetic operations, the chemical processing platform comprising: a network of two or more stations, optionally three or more stations, wherein each station is in direct and / or indirect material intercommunication with each of the other stations, and each station comprises one or more substations, wherein each substation in a first station is for executing a different automated synthetic operation to each substation in a second station; and an operation data collection unit for collecting operation data on the automated synthetic operation performed within the substations; and a control unit in signalling communication with the two or more stations and the operation data collection unit, wherein the control unit is for receiving operation data from the operation data collection unit, generating a machine-readable instruction set based on the automated synthetic procedure and the operation data, and providing the substation with the machine-readable instruction set for execution of the synthetic operation.

[0085] Each station, and each substation, can hold a reaction mixture and provides a means for performing a synthetic operation on the reaction mixture.

[0086] The stations are provided together in a network, of which there are two or more stations. The network of stations is configured to permit a reaction mixture to move therethrough, such that the reaction mixture can move from a first station into a second station.

[0087] The movement of the reaction mixture may be performed autonomously within the network. Alternatively, the movement of the reaction mixture may be performed manually, for example, by a human user.

[0088] Each station in the network is in direct and / or indirect material intercommunication with each of the other stations in the network. For example, the first station is in direct material intercommunication with the second station, or the first station is in indirect material intercommunication with the third station via the second station.

[0089] Also, a reaction mixture is permitted to be manually transferred by a human user from a first station into a second station. That is, the first station may also be in indirect material intercommunication with the second station via a human user by, for example, taking a reaction mixture out of the first station and transferring it into the second station. Thus, a reaction mixture provided within a station is directly accessible to a human user.

[0090] In addition to the station of the network, the platform may further comprise one or more external stations, wherein each external station is not in direct material intercommunication with the network, or with the stations within the network. Where the platform comprises an

[0091] 008773897 external station, transfer of a reaction mixture between a station of the network and the external station is facilitated by a human user.

[0092] By material intercommunication, it is meant that any material in the solid, liquid or gas phase can move between stations in the network. Preferably, the material intercommunication is a solid and / or liquid intercommunication, meaning that solid and / or liquid can move between stations in the network. Preferably, the material intercommunication is a fluid intercommunication, meaning that fluid (e.g., liquid and gas) can move between stations in the network. Preferably, the material intercommunication is a liquid intercommunication, meaning that liquid can move between stations in the network.

[0093] Each station comprises one or more substations, wherein each substation in a first station is for executing a different synthetic operation on the reaction mixture relative to each substation in a second station. Thus, the network comprises two or more stations, and each station comprises one or more substations, so as to form an array of individual units which are all connected together to each perform a synthetic operation.

[0094] Each station, such as each substation, is also in signalling communication with each other via a control unit. The control unit is for receiving operation data corresponding to a synthetic procedure from a human user, and is configured to generate an instruction set corresponding to a synthetic operation from the data.

[0095] In a third aspect of the invention, there is provided a system comprising a plurality of chemical processing platforms according to the second aspect in communication, and at least two chemical processing platforms in the system are remotely located from each other.

[0096] The plurality of chemical processing platforms may be in signalling communication via a cloud-based system.

[0097] In a fourth aspect of the invention, there is provided the use of the chemical processing platform of the second aspect for performing a synthetic procedure comprising a plurality of different synthetic operations.

[0098] These and other aspects and embodiments are described in further detail herein.

[0099] Summary of the Figures

[0100] The present invention is described with reference to the figures listed below.

[0101] Figure 1 is a schematic of a chemical processing platform according to an embodiment of the invention. The chemical processing platform comprises a network of three stations which are each in direct material intercommunication with each other. Each station

[0102] 008773897 comprises three substations. Each substation is both in direct material intercommunication with every other substation within the same station, and with every other substation within a different station by virtue of each station being in direct material intercommunication with each other.

[0103] Figure 2 is a schematic of the chemical processing platform according to an alternative embodiment of the invention. The chemical processing platform comprises a network of three stations, two pairs of which are in direct material intercommunication with each other, and a third pair, the two flank stations, are in indirect material intercommunication with each other via the middle station.

[0104] Figure 3a is a schematic of a method according to the first aspect of the invention. The method uses a chemical processing platform comprising two stations, each station having three substations, which are in direct material intercommunication and signalling communication with each other. The schematic shows the use of a synthetic procedure and operation data to generate instruction sets for automated synthetic operations. The operation data about the first automated synthetic operation is collected from the first (sub)station, and is used to generate a second automated synthetic operation for execution and performance in a second (sub)station; Figure 3b is a schematic of a method according to the first aspect of the invention, and is essentially an extension of the method shown in Figure 3a. The method uses a chemical processing platform comprising four stations, each station having three substations, which are in direct material intercommunication and signalling communication with each other. Operation data about each automated synthetic operation is collected from the each (sub)station, and is used to generate a further automated synthetic operation for execution and performance in a further (sub)station.

[0105] Figure 4 is a schematic of a method according to the first aspect of the invention. The method involves performing a plurality of automated synthetic operations, which are performed within (sub)stations of a chemical processing platform, and the reaction mixture is transferred through the network of (sub)stations. Operation data is collected alongside with the performance and execution of each automated synthetic operation. The combined operation data from each automated synthetic operation is aggregated to produce a library of operation data.

[0106] Figure 5 is a screenshot of preparation of 1-[5-(1-piperidyl)pyrazin-2-yl]ethan-1-one from 1- (5-chloropyrazin-2-yl)ethan-1-one and piperidine, according to Example 1.

[0107] Figure 6 is a LIPLC trace of the final product obtained at the end of Example 1.

[0108] Figure 7 is a1H NMR spectrum of the final product obtained at the end of Example 1.

[0109] Figure 8 is a13C NMR spectrum of the final product obtained at the end of Example 1.

[0110] 008773897 Figure 9 is a screenshot of a visualisation of the preparation of 1-[5-(1-piperidyl)pyrazin-2- yl]ethan-1-one from 1-(5-chloropyrazin-2-yl)ethan-1-one and piperidine using the monitoring system, in the form of a lifecycle plot, of the chemical processing platform. The abbreviations on the y-axis of the visualisation correspond to various substations of the network in which compilation occurred, and are given as follows: ILC: Inventory, Label, COSHH; RMC: Raw Materials Commissioning; SRQ: Setup, Reaction and Quenching; W: Work-up; E: Evaporation; P: Purification; A: Analysis (on NMR and LIPLC). Timestamps are provided at the start of an automated operation at each substation, and the reaction mixture is monitored according to the visual line across the lifecycle plot.

[0111] Detailed Description

[0112] The present invention provides a method of performing a synthetic procedure on a chemical processing platform and a chemical processing platform for performing a synthetic procedure. The methods of the present invention are for performing a synthetic operation on a reaction mixture based on synthetic procedures as initial input data, which may be provided by a human user, to generate an instruction set, collecting operation data from that synthetic operation, and generating an instructions set for a further synthetic operation based on the operation data.

[0113] In particular, the method focuses on generating new operation data based on a previous synthetic operation performed on a reaction mixture, and that the new operation data is used to inform the next synthetic operation within the plurality of synthetic operations for generating a final reaction product.

[0114] A synthetic operation refers to an execution or performance on a reaction mixture to alter or analysis its contents. Typically, but not always, the synthetic operation involves the transformation of a first reaction mixture into a different reaction mixture.

[0115] Aspects of the data acquisition, generation, and transfer, such as the input of synthetic procedures, the collection of the operation data and selection of such a further synthetic operation, are described in further detail below.

[0116] The methods of the invention are for performing a synthetic operation as performed by a chemical processing platform, and for collecting operation data from the synthetic operation performed therein.

[0117] In particular, the inventors have understood that an optimal use of the methods of the present invention involves a minimum amount of human input so as to provide an optimal level of versatility and a minimisation of cost.

[0118] 008773897 Thus, the combination of the autonomous collection of operation data together with the autonomous collection of operation data, the synthetic procedure, such as input data provided by a human user, may also be used to dynamically alter the instruction set, and thus to dynamically alter the synthetic operation.

[0119] The present inventors have also shown that by performing a plurality of synthetic operations on a reaction mixture, such that operation data is collected from each synthetic operation at each stage in the synthesis, the total aggregation of operation data at the end of the performance may be stored and used to inform future synthetic operations. The aggregated operation data may be known as a library of operation data.

[0120] Moreover, reference operation data from a previous synthetic operation (e.g., the library of operation data) may be used to validate a synthetic operation. The operation data from a synthetic operation may be compared to reference operation data (or the library of operation data). The comparison allows for the synthetic operation to be validated.

[0121] The instruction sets generated during the synthetic procedure may also be aggregated to give a library of instructions sets for the synthetic procedure. The aggregated instructions set is aggregated from the iterations of instructions sets generated and executed during the method of the invention. This aggregation of the instructions sets may be used to serialise a synthetic procedure, and provide the library of instructions sets. The aggregated instructions sets may be encrypted.

[0122] The library of instructions sets and library of operation data may be used together to allow for the serialisation of synthetic procedures, which can be reproduced and validated against past operation data.

[0123] The chemical processing platform comprises a network of stations which are in direct and / or indirect material intercommunication with each of the other stations.

[0124] The present inventors have exemplified the design, construction of an automated chemical processing platform to execute multi-step synthetic steps. The chemical processing platform comprises a network of stations which are in direct and / or indirect material intercommunication with each of the other stations.

[0125] The present inventors have shown that a network of stations is capable of performing synthetic operations by moving a reaction mixture across the platform. This is done by allowing the reaction mixture to move between a first station and a second station. Each station in the network is configured to perform a different synthetic operation, and employs a control unit which provides signalling communication across the network. The chemical processing platform may be used in synthesis, discovery, analysis and data acquisition.

[0126] 008773897 Within the network itself, there is comprised two or more stations, such as three or more stations. Each station further comprises one or more substation which is each for executing a different automated operation on the reaction mixture relative to a substation of a different station.

[0127] The inventors have also understood that an optimal use of the chemical processing platform of the present invention involves a minimum amount of human input so as to provide an optimal level of versatility and a minimisation of cost.

[0128] Thus, the stations may be connected, for example by a human user, in various different arrangements and connections, such as one-to-one, one-to-many, many-to-one and many- to-many. The stations may also be connected in such a manner such that movement of the output reaction mixture of a first station into a second station is performed by a human user. Advantageously, the workflow can loop in any order and processes on each station can be adjusted to facilitate these transitions.

[0129] This concept is in contrast to fully end-to-end automated workflows which may lose the natural versatility of humans, and are also usually susceptible to high operational costs.

[0130] The prior art generally describes methods and systems for performing automated chemical syntheses which require a centralised platform for receiving, storing and displaying reaction information.

[0131] The present inventor has previously described in WO 2019 / 170772 a system comprising a plurality of synthesisers that are in communication via a communal reporting platform, such as a social media platform, wherein the synthesisers are for the automated synthesis of one or more chemical or biological reactions. Dubbed the Twitterbot, this cooperative system provides an automated process for chemical or biological synthesis using a network of automated synthesisers which are each capable of performing chemical reactions, analysing them, and using the internet to communicate data using a controller for each synthesiser.

[0132] According to Twitterbot, each synthesiser performs its own automated synthesis independently to every other synthesiser in the system, only communicating via a communal reporting platform. The chemical reactions, and reagents, intermediates and products thereof, do not directly flow through the system across multiple synthesisers. Therefore, while these systems perform experiments in an automated fashion, they are limited in their interoperability and modularity, which are crucial for integrating modules, instruments and software platforms together to communicate and collaborate efficiently without requiring a centralised reporting platform as a common hub. WO 2019 / 170772 does not relate to performing a synthetic procedure comprising a plurality of different synthetic operations on a chemical processing platform comprising a network of two or more stations, where the method involves the generation, collection and use of operation data.

[0133] 008773897 The present inventor has also previously described in WO 2024 / 061972 methods and apparatus for performing a chemical synthesis, and for characterising the chemical synthesis in a form of a profile, or fingerprint, for comparison against a reference profile. The profile is intended to provide validation for the chemical synthesis such that a user can assume the identity and the quality of a product based on the profile that is generated during its production in the chemical synthesis. In this earlier work, the use of profiles and reference profiles provides a measure of the quality of the chemical synthesis against the approved synthesis, such that the chemical synthesis may be managed to bring it into line with the profile. WO 2019 / 170772 also does not relate to performing a synthetic procedure comprising a plurality of different synthetic operations on a chemical processing platform comprising a network of two or more stations, where the method involves the generation, collection and use of operation data.

[0134] US 5684711 describes a computer-based, iterative process for generating chemical entities with desired properties. The process involves generating a chemical library from robotic synthesis instructions, analysing these compounds in the chemical library to obtain structureactivity data, comparing this structure-activity data with prescribed data to identify new compounds, and generating new instructions and identifying reagents to produce those new compounds. However, the process in US 5684711 is only iterative in the context of optimising an overall synthesis. It does not describe that the next iteration is the next step of a synthetic procedure which comprises a plurality of different synthetic operations, so there is no dynamic adjustment of future synthetic operations within the synthetic procedure.

[0135] US 5684711 does not describe a synthetic procedure which is a plurality of different synthetic operations. The data obtained from the previous ‘step’ of a synthesis does not inform how the next ‘step’ is carried out.

[0136] The methods and chemical processing platform of the present involve performing synthetic operations on a reaction mixture. The reaction mixture contains at least one compound. The reaction mixture may be a reagent, intermediate or product thereof.

[0137] The nature of the reaction mixture may change after a synthetic operation is performed on it. For example, a reaction mixture may undergo a synthesis operation to obtain a crude mixture of a reaction product. Alternatively, the nature of the reaction mixture may stay the same after a synthetic operation is performed on it. For example, a reaction mixture may undergo an analysis operation, wherein the analysis operation is performed by an I R spectrometer.

[0138] The reaction mixture may suitably be a chemical or biological mixture. The reaction mixture may comprise a chemical or biological reagent, intermediates or products thereof.

[0139] 008773897 The present invention also provides a plurality of chemical processing platforms that are in signalling communication, wherein at least two chemical processing platforms, such as each chemical processing platform, in the system are remotely located from each other. The chemical processing platforms may be in signalling communication using any suitable means, such as via a cloud-based system.

[0140] The present invention also provides the use of the chemical processing platform for performing a synthetic procedure comprising a plurality of different synthetic operations.

[0141] Exemplary and preferred stations and substations of the chemical processing platform are described in further detail below, together with a description of their use in performing synthetic operations on chemical and biological reactions.

[0142] The chemical processing platform and system are for use in the methods of the invention.

[0143] Synthetic Operations

[0144] The methods of the invention relate to performing a synthetic procedure. The synthetic procedure comprises a plurality of different synthetic operations.

[0145] The synthetic procedure may be based on literature synthetic procedures in natural language. The method includes collecting operation data from the synthetic operations performed on the reaction mixture to inform the next synthetic operation to be performed. The synthetic operations may be performed and executed autonomously on a chemical processing platform.

[0146] The methods may be used for various synthetic procedures, for example, to prepare chemical and biological products from starting materials.

[0147] The methods of performing synthetic operations described herein involves sending and receiving reaction mixtures, and selecting synthetic operations to be performed (such as autonomously performed) on the reaction mixtures. Each synthetic operation is performed and executed based on an instruction set which is generated based on the synthetic procedures and operation data.

[0148] The synthetic operation is not particularly limited and may encompass methods for the production of small organic compounds, metal complexes, supramolecular structures and polymers, amongst others.

[0149] The synthetic operation may also involve preparing a reaction mixture for a chemical reaction, as well as working-up of a reaction mixture following a chemical reaction, purifying a product of a chemical reaction, and analysing a product of a chemical reaction.

[0150] 008773897 The methods may comprise a series of synthetic operations, as well as parallel synthetic operations, that are later brought to convergence for the production of a target reaction product.

[0151] The synthetic operations may be convergent. For example, reactions may be brought to convergence for at least a final synthetic operation step. Synthesis operations may be executed in parallel, or purification operations may be executed in parallel, analysis operations may be executed in parallel.

[0152] Typically, a method of performing a plurality of synthetic operations may comprise one or more of work-up, purification, or synthesis steps. These steps may be succeeded by an immediate analysis step, to analyse the chemical or biological mixture immediately after the preceding step.

[0153] Thus, in a first aspect of the invention, there is provided a method of performing a synthetic procedure on a chemical processing platform, as described herein.

[0154] By way of illustration, the worked examples provided in the present case exemplify the methods of performing a plurality of synthetic operations to provide a stepwise synthesis of the organic compound, 1-[5-(1-piperidyl)pyrazin-2-yl]ethan-1-one.

[0155] Synthetic Procedure

[0156] Preceding step (a), the method may comprise a step of providing a synthetic procedure from a human user. The synthetic procedure comprises a plurality of different synthetic operations.

[0157] The synthetic procedure may be provided in natural language. The synthetic procedure may be provided in a machine-readable language, such as XDL.

[0158] A synthetic procedure is a description of a method of making a chemical product. A synthetic procedure typically comprises the different experimental operations or steps required to produce the product. It may comprise information on the different reagents (e.g. starting materials and reactants), solvents and catalysts, and the quantities required, to produce the product. It may comprise information on any specialist equipment needed. However, it is typical for a synthetic procedure to omit certain specific information that may be deemed obvious to a skilled chemist. Typically, information on the necessary equipment is omitted. Similarly, information on work-up (e.g. quenching of the reaction mixture), flushing (e.g. with inert gases), washing, extraction and purification steps is also omitted.

[0159] 008773897 The synthetic procedure may be provided in natural language from a human user, such as a human user providing synthetic procedure electronically through the chemical processing platform.

[0160] The synthetic procedure may be provided via manual input into a software platform by a human user, such as a human user providing synthetic procedure electronically through the chemical processing platform.

[0161] The synthetic procedure may be provided by extracting the synthetic procedure from literature.

[0162] The synthetic procedure may be provided by extracting the synthetic procedure from a synthetic procedure library, such as a library of instructions sets.

[0163] A synthetic procedure is typically found in an academic journal article in the chemical, biological or materials sciences. It may be located either in the main text of the article, or in the associated supplementary information. A synthetic procedure may also be found in other academic texts, such as a review article, letter or book. It may be found in a specialised synthetic textbook or a laboratory standard operating procedure. Dedicated web repositories for synthetic procedures are also known (e.g. http: / / www.orgsyn.org). They may also be found in teaching materials, such as a general textbook or a laboratory procedure. The procedure may also be set out in a thesis, or a company report.

[0164] Synthetic procedures are typically in natural language. That is, in free, unstructured text. For example, in prose, such as in encrypted prose. These natural language synthetic procedures are suitable for use in the present invention.

[0165] The method may comprise an optional pre-processing step. The pre-processing stage can be used to simplify and shorten the natural language synthetic procedure to make the subsequent processing stages quicker. Several pre-proceedings steps may be included. The pre-processing steps are performed automatically.

[0166] The pre-processing step may comprise performing optical character recognition (OCR) on the document displaying the natural language synthetic procedure. OCR converts an image of text, such as scanned text or a photograph of text, into machine-encoded text. Thus, including OCR enables the method to use scanned or photographed synthetic procedures from physical (hard-copy) articles or handwritten notebooks.

[0167] The pre-processing step may comprise removing HTML from the synthetic procedure.

[0168] HTML code is typically included in synthetic procedures contained in an electronic database.

[0169] For example, synthetic procedures in the Reaxys database typically contains HTML code. It

[0170] 008773897 is not necessary to understand the HTML in order to extract an instruction set from the synthetic procedure.

[0171] The pre-processing step may comprise removing formatting markings from the synthetic procedure. For example, the pre-processing steps may comprise removing formatting marks indicating italicisation, emboldening and underling.

[0172] The pre-processing step may comprise removing non-printing characters from the synthetic procedure. For example, the pre-processing step may comprise removing tabs and paragraph markers (carriage returns). Non-breaking characters may be replaced with standard counterparts (e.g. replacement of a non-breaking space with a space).

[0173] The pre-processing step may comprise removing analytical data from the synthetic procedure. Analytical data includes, for example, NMR, I R, melting point and mass spectrometry data. This analytical data can be useful for verifying the identity of chemical compounds, for example, the final product. This analytical data may be termed characterisation data. Characterisation data is typically found at the end of a synthetic procedure, or at the end of each step within a synthetic procedure. However, characterisation data is not necessarily required for the extraction of the instruction set. Removing the characterisation data in a pre-processing step reduces the text, speeding up subsequent steps.

[0174] Certain analytical data may be useful for performing the synthetic procedure. For instance, analytical data defining the end-point of a reaction or synthetic operation. For example, where a synthetic procedure requires a synthetic operation to be performed until a given colour change is observed, or until a certain peak within the chromatograph of the reaction mixture disappears. This analytical data may also include the appearance or disappearance of specific peaks within an NMR or IR spectrum of the reaction mixture. This analytical data may be termed reaction-monitoring data. Reaction monitoring data is typically found embedded within the text of the natural language synthetic procedure. Optionally, this analytical data may be retained in the synthetic procedure.

[0175] The pre-processing may comprise normalising the text. This transforms the text into a consistent format. For example, normalising the text may comprise inserting missing spaces after full stops or before certain units, such as “°C”.

[0176] The pre-processing step may comprise translating the text, for example, translating the text from German, French, Chinese, Japanese, Korean or Russian into English. The method may use a single language, preferably English, for standardisation within the system.

[0177] The pre-processing step may include de-encrypting the synthetic procedure. Any suitable de-encryption may be used.

[0178] 008773897 Finally, the pre-processing step may include making specific replacements to standardize the appearance of certain phrases. For example, words denoting numbers may be replaced with their respective numerals (e.g. replacement of “ninety nine” with “99”). Full stops that denote abbreviations may be removed (e.g. replacement of “min.” in the phrase “5 min.” with “min” to give “5 min”). The different characters used to represent the degree symbol may be replaced with the standard symbol (e.g. replacement of the letter o in superscript “°” or “°” or the ordinal indicator “°” with the degree symbol “°”).

[0179] Instruction Set

[0180] In step (a), the method comprises generating an instruction set for a first synthetic operation from the synthetic procedure using the control unit.

[0181] An instruction set comprises a list of the individual coded operations needed to perform a synthesis. In some embodiments, the instruction set can be interpreted by the chemical processing platform, and the platform can act upon that instruction set. Thus, the instruction set is machine-readable. The instruction set may also be human-readable, such as being capable of conversion into prose. In some embodiments, the instruction set can be interpreted by the chemical processing platform, and the platform can provide a human- readable instruction set. This allows the instruction set to be executed autonomously on the station, executed manually on the station by a human user, or using a mix of autonomous and human execution. That is, the instruction set may comprise instructions for autonomous execution and / or instructions for human execution. How the instructions set is executed may depend on the nature of the synthetic operation to which the instruction set relates.

[0182] How the instructions set is executed may also depend on the nature of the chemical processing platform. If the platform has the hardware capability to carry out an instruction set autonomously then the instructions set may be used for autonomous execution. Alternatively, if the platform does not have the hardware capability to carry out an instruction set autonomously then the instructions set may be used for human execution. Also, if the platform does not have the hardware availability to carry out an instruction set autonomously (e.g., because the required hardware is present but carrying out another synthetic operation) then the instructions set may be used for human execution. Typically, the instruction set comprises instructions for a combination of autonomous execution and human execution.

[0183] The instruction set may be in any suitable machine-readable format. Typically, the instruction set is in a mark-up language, such as a descriptive mark-up language, such as a chemical descriptive mark-up language, for example XML or XDL. The preferred format for the instruction set is a mark-up language adapted for chemical synthesis, such as XDL. XDL is described in (Steiner). XDL is a universal chemical programming language standard and

[0184] 008773897 format which allows end-to-end chemical procedures to be described in a general, platformindependent manner.

[0185] The generation of the instruction set from the tagged synthetic procedure may comprise an interpretation step and a conversion step.

[0186] The interpretation step may take the synthetic procedure and extracts a list of Actions, each action accompanied by a list of Modifiers. The interpretation step combines Modifiers with Actions. Typically, Modifiers are combined with Actions based on their relative position (proximity) in the natural language synthetic procedure. The interpretation step comprises combining the Action and Modifier pairs with the Subjects to generate an operation list.

[0187] The conversion step may comprise converting the operation list into an instruction set. An instruction set is a machine-readable list of the operations that need to be carried out in order to perform a synthesis.

[0188] The generation of an instruction set from a synthetic procedure is performed and coordinated entirely within the control unit of the chemical processing platform, and without further input from the human user. Thus, step (a) is typically performed autonomously.

[0189] In parallel to generating an instruction set, step (a) may also comprise the generation of tangible information, which may be visible and useful for a human user who is carrying out the methods of the present invention.

[0190] For example, step (a) may comprise a step of generating a producing a safety document corresponding to the plurality of synthetic operations to be performed on the chemical or biological mixture. This further step is automated by the chemical processing platform to analyse the contents of the chemical or biological mixture for risk and safety.

[0191] Typically, the safety document may be a Control of Substances Hazardous to Health (COSHH) form. The COSHH form may be automatically generated, and is useful to ensure safety in a laboratory for a human user and compliance with chemical handling and laboratory best practices.

[0192] The method may also comprise generating an instruction set for performing a plurality of synthetic operations in parallel. For example, a single instruction set may be used to provide instructions for how to execute two or more synthetic operations, where the two or more synthetic operations may each be the same or different, and preferably are each the same. Where the synthetic operations are each the same, using a single instruction set may reduce the number of steps required of the chemical processing platform. For example, a step may be grouped into a single instruction (below). This may result in improved action economy.

[0193] 008773897 The method may also comprise generating a plurality of instruction sets for each synthetic operation to be performed from the synthetic procedure.

[0194] Thus, each synthetic operation may be ready for execution, based on generating a plurality of instruction sets with the control unit in step (a), before executing the first synthetic operation on a first reaction mixture in step (b). In this case, the instruction sets for later operations may be modified based on operation data obtained when executing earlier synthetic operations.

[0195] In addition to step (a), in step (d), the method also comprises generating an instruction set for a second synthetic operation from the synthetic procedure and from the first operation data with the control unit. As described herein, the operation data is collected from the first synthetic operation by the operation data collection unit, and this is step (c). The second synthetic operation may be a direct modification or adaptation of the instruction set generated in step (a), based on operation data.

[0196] Thus, in some embodiments, the step of generating an instruction set for a second synthetic operation is based on the synthetic procedure and the operation data available for each synthetic operation in the synthetic procedure.

[0197] Accordingly, the method comprises generating further instruction sets for further synthetic operations. These further instruction sets are derived from the combination of the synthetic procedure and operation data collected by the chemical processing platform as described herein. Importantly, the operation data collected by the operation data collection unit, such as in step (c), may be used to inform and alter a further instruction set, and thus a further synthetic operation.

[0198] When an instruction set for a synthetic operation is generated, the synthetic operation may be made visible from the chemical processing platform to a human user. In addition, the human user can see the synthetic operation to be performed. In this way, the human user may be able to execute the synthetic operation themselves. That is, the synthetic operation may be visualised. The human user may therefore be informed on the likely transition that will be undergone from a first chemical or biological mixture to a second chemical or biological mixture. The human user may therefore be permitted to manually transfer the chemical or biological mixture, as described further below.

[0199] The instruction sets generated during the synthetic procedure may also be aggregated to provide a library of instructions sets. The instruction sets are typically aggregated from the iterations of instructions sets generated and executed during the method of the invention. The instruction sets are typically aggregated from the iterations of instructions sets generated and executed during the synthetic procedure. The aggregation process may identify the best performing instruction set for each synthetic operation, and aggregate the

[0200] 008773897 best performing instructions sets to provide the library of instructions sets. The best performing instructions sets may be identified by analysis of the operation data.

[0201] This aggregation of the instructions sets may be used to serialise a synthetic procedure, and provide the library of instructions sets. The library of instructions sets may be encrypted.

[0202] The instruction sets generated during the synthetic procedure may be aggregated with operation data to provide a library of instructions sets and operation data. The library of instructions sets and operation data may be used together to allow for the validation of future synthetic procedures. Future synthetic procedures using the library of instructions sets can be compared against the library of operation data, in order to validate the synthetic procedure.

[0203] The method therefore also provides a step of generating a library of operation data and a library of instruction sets. The library of operation data and a library of instruction sets may be used during the generation of future instructions sets.

[0204] The instruction set may be encrypted to provide data security to the platform. The library of instruction sets may be encrypted and / or the library of operation data may be encrypted. Any suitable encryption may be used.

[0205] Synthetic Operation

[0206] In step (b), the method comprises executing the first synthetic operation on a first reaction mixture to obtain a second reaction mixture. The first synthetic operation is carried out using a first substation, as described herein.

[0207] The synthetic operation is executed according to the instruction set. For example, the first synthetic operation is executed according to the instruction set for the first synthetic operation. Similarly, the second synthetic operation is executed according to the instruction set for the second synthetic operation.

[0208] A synthetic operation is the execution or performance of a synthetic step on a reaction mixture to alter or analyse its contents.

[0209] Where a synthetic operation is an alteration, the synthetic operation involves the transformation of a first reaction mixture into a different reaction mixture. Typically, but not always, the synthetic operation is an alternation.

[0210] Where a synthetic operation is an analysis, the second reaction mixture is identical to the first reaction mixture. For example, the synthetic operation performed on the reaction mixture is a non-invasive analytical technique.

[0211] 008773897 A synthetic operation is typically a synthetic operation which is performed autonomously on the chemical processing platform. The synthetic operation is typically performed and executed when the reaction mixture is prepared and ready within the chemical processing platform.

[0212] In addition or alternatively, the synthetic operation may be performed by a human user on the chemical processing platform. The synthetic operation may be performed using a mixture of autonomous execution and execution by a human user on the chemical processing platform.

[0213] The platform may record the number of synthetic operations carried out by a human user and the number of steps autonomously executed by the platform. The platform may record the time taken for synthetic operations carried out by a human user and the time taken for autonomously executed by the platform. The platform may report the recorded data. Such data may be used to inform future hardware development.

[0214] The execution of the synthetic operation is based on the instruction set, and may further comprise a compilation step. In this case, the instruction set may be a machine-readable instruction set.

[0215] For the programming language to be executable, the machine-readable instruction set may suitably be compiled into an executable format, which contains all the executable unit operations to carry out all the synthetic operations of a chemical processing platform. In some embodiments, step (b) is preceded by a step of compiling the instruction set into an executable format. The executable format may be a format such as a Json file or an .xdlexe file.

[0216] By way of an example, where the instruction set is in XDL, the compilation process is described in Steiner. The core of the compilation process is the breakdown of the level XDL steps into their constituent sub-steps and the mapping of the platform hardware to the abstract XDL hardware. The mapped XDL is then solidified in an .xdlexe file. The .xdlexe file contains a hash of the graph representing the platform for which the file was compiled, and the file will only execute using a platform controller linked to this graph. Other platform specific alterations can also be made at this stage.

[0217] Execution of the instruction set on a chemical processing platform may result in the production of the final chemical product described in the synthetic procedure. The executable format of the instruction sets generated from Example 1 is shown in Annex 1.

[0218] The execution step involves carrying out the specific synthetic processes necessary to perform the synthetic operation. These operations typically include the transfer of reagents

[0219] 008773897 and solvents from the appropriate reservoirs to an appropriate reaction flask. Typically, the reaction required stirring and either heating or cooling.

[0220] Optionally, additional synthetic processes such as filtration, liquid-liquid extraction, chromatographic separation and evaporation may be required. The execution step may comprise transfer of the relevant reaction mixture to hardware specialised for those processes, along with operation of that hardware.

[0221] Optionally, analytical processes such as pH measurement (e.g. conductivity sensors), colour change measurement (e.g. cameras), LIV-VIS spectroscopy, IR spectroscopy, NMR spectroscopy, mass spectroscopy, liquid chromatography and gas chromatography may be required. These processes may be required for reaction monitoring (e.g. perform an operation until a given colour change is observed) or for characterisation of the final product. The execution step may comprise operation of the relevant hardware specialised for those processes, along with transfer of the reaction mixture to appropriate sampling equipment.

[0222] In addition to step (b), in step (e), the method also comprises executing the second synthetic operation on the second reaction mixture, and this step succeeds the step of generating an instruction set for the second synthetic operation, which is step (d). The second synthetic operation is carried out using a second substation, as described herein.

[0223] The synthetic operation is carried out according to the instruction set. For example, the second synthetic operation is carried out according to the instruction set for the second synthetic operation.

[0224] In general, the method may also comprise a step of executing an nthsynthetic operation on an nthreaction mixture. The nthsynthetic operation is carried out using a nthsubstation. That is, for a synthetic procedure comprising ‘n’ synthetic operations, the method may comprise steps of generating an instruction set, executing and collecting operation data for each of the ‘n’ synthetic operations.

[0225] For example, for a synthetic procedure having ‘n’ synthetic operations, the method may comprise:

[0226] (i) generating an instruction set for a nthsynthetic operation based on a synthetic procedure and the n-1thoperation data using the control unit;

[0227] (ii) executing the nthsynthetic operation on a nthreaction mixture to obtain a n+1threaction mixture using a nthsubstation;

[0228] (iii) collecting nthoperation data about the nthsynthetic operation performed on the nthreaction mixture using the operation data collection unit;

[0229] (iv) repeating steps (i) to (iii) for the n synthetic operations in the synthetic procedure.

[0230] 008773897 In some embodiments, the first synthetic operation is a synthesis step, and the second synthetic operation is an analysis step. Preferably, the third synthetic operation may be dependent on the outcome of the second synthetic operation following the first synthetic operation.

[0231] More generally, in some embodiments of the method, a nthsynthetic operation is a synthesis step using a nthreaction mixture to obtain a n+1threaction mixture, and the n+1thsynthetic operation is an analysis step of the n+1threaction mixture. Preferably, the n+2thsynthetic operation may be dependent on the outcome of the n+1thsynthetic operation following the nthsynthetic operation.

[0232] Upon completion of the first synthetic operation, the second synthetic operation may be an analysis step. The analysis step involves analysing the second reaction mixture produced from the first synthetic operation. By performing analysis of the second reaction mixture, the third synthetic operation may be determined from the outcome of the analysis step. For example, where the analysis step confirms that the first synthetic operation is a success, the third synthetic operation may be a step of isolating the desired reaction product from the second reaction mixture. Alternatively, where analysis confirms that the second reaction mixture is not a success, the third synthetic operation may be a purification step.

[0233] The ‘success’ of any reaction mixture may be defined whether or not the reaction mixture comprises the intended or desired reaction product having desired characteristics, such as a predetermined minimum yield and / or a predetermined minimum purity of the intended reaction product. If the reaction mixture satisfies a yield which is above the predetermined minimum yield and / or if the reaction mixture satisfies a yield which is above the predetermined minimum yield, it is considered a success. Whether or not the reaction mixture was a success following a synthetic step may be evaluated using an analysis step.

[0234] Therefore, a subsequent synthetic operation to be performed on the reaction mixture is dependent on the outcome of the analysis step.

[0235] More generally, the method may comprise:

[0236] (i) generating an instruction set for a nthsynthetic operation based on a synthetic procedure and the n-1thoperation data using the control unit;

[0237] (ii) executing the nthsynthetic operation on a nthreaction mixture to obtain a n+1threaction mixture using a nthsubstation;

[0238] (iii) collecting nthoperation data about the nthsynthetic operation performed on the n+1threaction mixture using the operation data collection unit;

[0239] (iv) generating an instruction set for a n+1thsynthetic operation based on the synthetic procedure and the nthoperation data using the control unit; and

[0240] (v) executing the n+1thsynthetic operation on the n+1threaction mixture to obtain a n+2threaction mixture using a n+1thsubstation, wherein the n+1thsynthetic operation is an

[0241] 008773897 analysis step and the n+1thsubstation is an analytical unit.

[0242] (vi) collecting n+1thoperation data about the n+1thsynthetic operation performed on the n+2threaction mixture using the operation data collection unit;

[0243] (vii) generating an instruction set for a n+2thsynthetic operation based on the synthetic procedure and the n+2thoperation data using the control unit; and

[0244] (viii) executing the n+2thsynthetic operation on the n+2threaction mixture to obtain a n+3threaction mixture using a n+2thsubstation, wherein the n+2thsynthetic operation and the n+2thsubstation are both dependent on the outcome of the n+1thsynthetic operation.

[0245] In some embodiments, the n+1threaction mixture and the n+2threaction mixture are the same. This may occur where the analysis step is non-destructive, so as to preserve the nature of the reaction mixture during analysis.

[0246] In some embodiments, the n+2thsynthetic operation is the step of isolating the desired reaction product from the n+1threaction mixture. Preferably, this type of n+2thsynthetic operation is selected where analysis confirms that the n+1threaction mixture comprises a desired reaction product, such as a desired reaction product having the desired characteristics.

[0247] In some embodiments, the n+2thsynthetic operation is a purification step to obtain at least a portion of the n+1threaction mixture. Preferably, this type of n+2thsynthetic operation is selected where analysis confirms that the n+1threaction mixture comprises the nthreaction mixture but does not comprise a desired reaction product, such as a desired reaction product having the desired characteristics. Then, the n+1threaction mixture can be regenerated and reused for further synthetic operations, thereby improving reagent efficiency.

[0248] Generally, the methods of the invention may be used to investigate and explore synthetic routes within the reaction space, and the methods may allow a future synthetic operation to be a repeat of a previous synthetic operation. For example, a synthetic operation to be repeated may be an automated analysis operation. Therefore, in some cases, the second synthetic operation is the same as the first synthetic operation. In some cases, the second synthetic operation is the same as a third synthetic operation.

[0249] Preferably, the method allows the repetition of a synthetic operation a limited number of times. For example, a synthetic operation may be repeated two times or less, preferably three times or less, more preferably four times or less. For example, a synthetic operation may be repeated from two to four times, preferably from two to three times.

[0250] In some embodiments, the synthetic operation is carried out only once. That is, the synthetic operation is not repeated.

[0251] 008773897 Preferably, a synthetic operation is repeated only if it is associated with a particular reaction outcome, such as an outcome that is associated with a benefit or a desirable outcome. In this way, the methods do not repeat reactions that are known to not work, or to otherwise produce undesirable results.

[0252] Reaction Mixture

[0253] A reaction mixture may comprise a reagent, or intermediates or products thereof. The reaction mixture may suitably be a chemical or biological mixture. A chemical or biological mixture may comprise a chemical or biological reagent, or intermediates or products thereof. The chemical or biological mixture is typically physically transferred through the chemical processing platform.

[0254] The platform may select appropriate reagents for the reaction mixture. A user may be permitted to select a reagent which is available in the platform. Where a reagent selected by a user is not available, the platform may select a suitable alternative reagent.

[0255] The chemical or biological mixture may be transferred by a human user, such as by removing the chemical or biological mixture from one part of the chemical processing platform to another part of the chemical processing platform.

[0256] The chemical processing platform may provide a visualisation of the synthetic operations performed, including the status of the synthetic operation.

[0257] When the synthetic operation performed on the reaction mixture is complete, the visualisation may monitor the status and provide an indication for the human user for transfer of the reaction mixture to a different part of the chemical processing platform for further synthetic operations. When the plurality of synthetic operations is complete, the visualisation may provide an indication for the human user to remove the reaction mixture from the chemical processing platform so that it can be used in post-processing.

[0258] In some embodiments, step (e) is preceded by a step of transferring the second reaction mixture from the first substation to the second substation of the chemical processing platform.

[0259] The reaction mixture may also be transferred autonomously through the chemical processing platform, such as by using flow chemistry. Thus, in some embodiments, the step of transferring the second reaction mixture is performed manually.

[0260] Alternatively, in some embodiments, the step of transferring the second reaction mixture is performed manually.

[0261] 008773897 In a typical use case, the second reaction mixture may differ from the first reaction mixture in step (b). For example, where the first synthetic operation is a synthesis step on reagents, such as in a synthetic substation of the chemical processing platform as described herein, the obtained reaction mixture may contain a crude reaction product. Consequently, subsequent purification in a purification substation of the chemical processing platform as described herein, may be necessary.

[0262] In other cases, the second reaction mixture may be the same as the first reaction mixture, for example when the first reaction mixture undergoes a non-invasive and non-destructive analysis step, such as in an analysis substation of the chemical processing platform as described herein.

[0263] Therefore, the nature of the second reaction mixture relative to the first reaction mixture depends on the specific synthetic operation performed on the first reaction mixture, and the selection of the further synthetic operation is informed by the combination of synthetic procedure and operation data.

[0264] Operation Data

[0265] In step (c), the method comprises collecting first operation data about the first synthetic operation performed on the first reaction mixture using an operation data collection unit.

[0266] Operation data refers to data which is generated, collected, and used when carrying out the methods of the present invention using the chemical processing platform. Preferably, operation data refers to data which is generated, collected, and used autonomously when carrying out the methods of the present invention using the chemical processing platform. Similar to the synthetic procedure which may be provided by a human user preceding step (a), operation data may also correspond to a synthetic procedure.

[0267] More typically in the present methods, operation data includes information about the first reaction mixture, information about the second reaction mixture, and information about the transition from first reaction mixture to the second chemical or biological mixture. Since the transition is facilitated by executing a synthetic operation on the first reaction mixture, the operation data also includes information about the effectiveness of the synthetic operation.

[0268] In particular, operation data includes information about the status of the present synthetic operation which concurrently occurs within the chemical processing platform. The operation data may include, but is not limited to, data on substrates, reagents, reaction conditions, such as temperature, expected and actual reaction products.

[0269] The operation data may be collected using any suitable means. The operation data measurement device may be a temperature probe, pressure probe, flow meter, colorimeter,

[0270] 008773897 camera, UV-Vis spectrometer, mass spectrometer, an IR spectrometer, a hyperspectral imaging spectrometer, a Raman spectrometer, an X-ray spectrometer, an NMR spectrometer. The operation data measurement device is typically a temperature probe, pressure probe, flow meter, colorimeter, or camera.

[0271] The operation data may be temperature, pressure, flow-rate, colour, camera data, UV-Vis data, mass data, IR data, a hyperspectral imaging data, a Raman data, an X-ray diffraction data or NMR data. The operation data is typically temperature, pressure, flow-rate, colour, or camera data.

[0272] The operation data is collected over time. Each unit of operation data is associated with a point in time in which it is collected. Each unit of operation data is associated with the configuration of the chemical processing platform, station, and / or substation at the point in time at which the data is collected.

[0273] The operation data may include changes in operation data over time, and rates of change in operation data over time. For example, the operation data may include changes or rates of change in temperature, pressure, flow-rate, colour, or camera data over time.

[0274] The methods of the present invention make use of operation data collected from each synthetic operation performed on each reaction mixture, to dynamically inform future synthetic operations.

[0275] Thus, the method may also comprise collecting operation data about each synthetic operation performed on each reaction mixture. For example, the method may comprise collecting nthoperation data about the nthsynthetic operation performed on the nthreaction mixture using the operation data collection unit.

[0276] Operation data may be made accessible across the entire chemical processing platform, such as in each station and each substation which may hold the reaction mixture.

[0277] In some embodiments, step (c) and step (d) occur concurrently. That is, collecting first operation data may occur while executing the first synthetic operation on a first reaction mixture to obtain a second reaction mixture.

[0278] Validation of Synthetic Operation

[0279] In step (f), the method comprises comparing the operation data from a synthetic operation to reference operation data, and validating the synthetic operation based on the comparison to the reference operation data. Preferably, the reference operation data is a library of operation data generated by aggregating operation data on two or more synthetic

[0280] 008773897 operations. The following discussion is applicable to a library of operation data (as described herein).

[0281] Typically, the reference operation data is generated during execution of a synthetic operation using the same reagents and conditions. Preferably the reference operation data is generated during execution of a synthetic operation using same instruction set. In this case, the operation data should be similar to the reference operation data. The degree of similarity of the operation data to the reference operation data can be used to validate the synthetic operation.

[0282] The reference operation data may be generated from operation data over the time course of a synthetic procedure, and it may be regarded as a characterisation of the synthetic procedure. The reference operation data may be completed once the plurality of different synthetic operations are each executed. However, any comparison with reference operation data need not be delayed until the completion of the synthetic procedure.

[0283] A visual representation of the operation data may be made available to the user for reference. This operation data may also be displayed with one or more reference profiles, to allow the user easy understanding of the reaction performance against a reference synthetic procedure.

[0284] This permits a user to assess the success of any chemical synthesis preformed, and also allows the user to recognise failures in expected performance, for example where there is a divergence in the operation data from the reference operation data. This allows the synthetic operation to be validated.

[0285] The comparison may itself provide validation for the synthetic procedure and may provide a guarantee that the synthetic procedure has been conducted in an appropriate manner, and consistent with the reference synthetic procedure. In this way, a third party can assume the identity and the quality of a product based on the profile that is generated during its production in the chemical synthesis.

[0286] Similarly, where there is a significant difference between the operation data and the reference operation data, then it can be understood that the chemical synthesis was not performed according to the approved synthesis, whether unintentionally or by design. Where the operation data for a synthetic procedure departs from the reference operation data, the synthetic procedure may be managed to bring it into line with the profile, or the synthetic procedure may be abandoned, as the product of the process will be deemed not the have the necessary reaction profile matching that of the approved process.

[0287] The reference operation data may be characteristic of a reaction that yields a desired product, optionally also having a desirable level of purity. The reference operation data may

[0288] 008773897 also be characteristic of a synthetic procedure for a desired product that is performed under desirable conditions. Thus, whilst there may be many ways to access a desired product at a desired level of purity, the reference operation data may reflect the process that is regarded as most appropriate for the operator or the capabilities of the chemical processing platform, for example owing to the simplicity of the reaction conditions, the available reactionware and the number of steps, for example.

[0289] The reference operation data may be provided together with an instruction set for modifying a chemical synthesis for the purpose of bring about a desirable result.

[0290] Where remedial action is required, the chemical processing platform may operate autonomously to bring about a change in the reaction conditions, as described herein.

[0291] Additionally, or alternatively, the chemical processing platform may call for the intervention of the user to effect a change in the synthetic procedure.

[0292] Where a reaction deviates from the reference profile it may do to such an extent that it is not practicable to resolve, or such deviations may be associated with a problem in the reaction conditions that is irresolvable, and for such reasons the system or the user may decide to entirely abandon a chemical synthesis in favour of restarting the synthesis, and optionally together with a reconstruction of the reactionware for the chemical processing platform, if such was deemed necessary.

[0293] Here, then a synthetic procedure may be discarded, and the system may be reset for a further attempt at performing the synthetic procedure, and for the attempted production of a target product.

[0294] In this way, the invention provides for error correction and verification of a synthetic procedure performed on the chemical processing platform.

[0295] Aggregation of Operation Data

[0296] As noted previously, it is important for the methods of the present invention to synthesise, and alter and adapt the synthesis of, chemical and biological products in order to explore the chemical space and to generate new routes of synthesis. The method of the first aspect of the invention achieves this by carrying out a second synthetic operation based on the synthetic procedure and the operation data from the first synthetic operation.

[0297] Further embodiments of the method build on this by seeking to generate a library of operation data from a plurality of synthetic operations performed on an initial reaction mixture. The library of operation data may then be made available for a human user in the form of synthetic procedures, such as in natural language.

[0298] 008773897 Thus, the method may comprise executing a two or more synthetic operations on a reaction mixture, optionally three or more synthetic operations, on an initial reaction mixture, collecting operation data about each synthetic operation, and aggregating each operation data to generate a library of operation data. The synthetic operations may be executed in series. The operation data may be collected in the same way as described herein. The initial reaction mixture may be transformed into a final reaction mixture. Typically, the final reaction mixture may be a final reaction product, such as a purified final reaction product. Thus, the method also relates to obtaining a final reaction mixture.

[0299] The method may also comprise executing a plurality of three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, or ten or more synthetic operations. Each synthetic operation may be a different synthetic operation. The number of synthetic operations may be dependent on the complexity of the overall synthetic procedure to transform the initial reaction mixture to the final reaction mixture.

[0300] In some embodiments, the method comprises generating an instruction set for the synthetic operation on the reaction mixture based on the synthetic procedure and the library of operation data. In some embodiments, the method also comprises generating an instruction set for a different synthetic operation on a reaction mixture based on the synthetic procedure and the library of operation data.

[0301] The library of operation data aggregated may be used for generating a plurality of instructions for a plurality of future synthetic operations. The future synthetic operations may be different to the synthetic operations already performed. The synthetic operations are typically intended to be performed on the same initial reaction mixture.

[0302] By executing a plurality of synthetic operations, the method of obtaining the final reaction mixture from the initial reaction mixture may be considered complete. Each completion of obtaining a final reaction mixture produces a library of operation data which is associated with the completion from the initial reaction mixture. By performing a plurality of synthetic operations, and a plurality of completions, the library of operation data may be continually expanded.

[0303] Typically, a chemist may want to explore alternative synthetic routes to the final reaction mixture from a particular starting reaction mixture. In some cases, a chemist who is looking to improve and optimise a route of chemical synthesis using a particular starting reaction mixture to arrive at a final reaction mixture may use a future synthetic operation which provides a more efficient plurality of synthetic operations, such that these are different to the synthetic operations already performed.

[0304] 008773897 In some embodiments, the method involves generating a plurality of instructions for a plurality of future synthetic operations from the library of operation data. This generation is typically performed on a control unit of the chemical processing platform. Preferably, this generation is performed autonomously. Preferably, the plurality of future synthetic operations is associated with producing a final reaction mixture having desirable characteristics.

[0305] Thus, it is advantageous to generate many different instructions for many different synthetic operations after obtaining a final reaction mixture from an initial reaction mixture.

[0306] Chemical Processing Platform

[0307] In a second aspect of the invention there is provided a chemical processing platform for performing a synthetic procedure, wherein the synthetic procedure comprises a plurality of synthetic operations, the chemical processing platform comprising: a network of two or more stations, optionally three or more stations, wherein each station is in direct and / or indirect material intercommunication with each of the other stations, and each station comprises one or more substations, wherein each substation in a first station is for executing a different synthetic operation to each substation in a second station; and an operation data collection unit for collecting operation data on the synthetic operation performed within the substations; and a control unit in signalling communication with the two or more stations and the operation data collection unit, wherein the control unit is for receiving operation data from the operation data collection unit, generating an instruction set based on the synthetic procedure and the operation data, and providing the substation with the instruction set for execution of the synthetic operation.

[0308] A station refers to an operational array which comprises one or more substations. A substation is an individualised and discrete physical operational unit which is configured to hold a reaction mixture, and which is configured to perform a synthetic operation on the reaction mixture.

[0309] The substations may be operated autonomously, for example, to carry out the execution step autonomously. In addition, or alternatively, the substations may be operated by a user, for example, such that the execution step is carried out by a user. The substations may be operated semi-autonomously, for example, to carry out part of the execution step autonomously and part by a user.

[0310] The stations are provided together in a network. The network comprises two or more stations, such as three or more stations, such as four or more stations. Thus, the network also comprises two or more substations, such as three or more substations, such as four or

[0311] 008773897 more substations. Typically, the number of substations in the network is greater than the number of stations in the network.

[0312] The network of stations is configured to permit a reaction mixture to move therethrough, such that the reaction mixture can move out from a first station into a second station. The movement of the reaction mixture may be performed autonomously by the chemical processing platform, or the movement of the reaction mixture may be performed manually by a human user.

[0313] Each station in the network is in direct and / or indirect material intercommunication with each of the other stations in the network. Since each station in the network is in direct and / or indirect material intercommunication with each of the other stations in the network, each substation within a station is also in direct and / or indirect material intercommunication with each of the other substations in each of the other stations in the network.

[0314] By direct material intercommunication, a reaction mixture is permitted to move from a first station into a second station, such that the first station is in direct material intercommunication with the second station. Referring to Station A and Station B, an example of this is shown in Figure 2.

[0315] Preferably, the direct material intercommunication is a direct solid and / or liquid intercommunication, meaning that solid and / or liquid can move between stations in the network. More preferably, the direct material intercommunication is a direct fluid intercommunication, meaning that fluid (e.g., liquid and gas) can move between stations in the network. Yet more preferably, the direct material intercommunication is a direct liquid intercommunication, meaning that liquid can move between stations in the network.

[0316] By indirect material intercommunication, a reaction mixture is permitted to move from a first station into a third station through a second station, and the first station is in indirect material intercommunication with the third station via the second station. In some cases, the second station does not perform a synthetic operation on the reaction mixture during movement of the reaction mixture from the first station to the third station via the second station. Referring to Station A and Station C, an example of this is shown in Figure 2.

[0317] Preferably, the indirect material intercommunication is an indirect solid and / or liquid intercommunication, meaning that solid and / or liquid can move between stations in the network. More preferably, the indirect material intercommunication is an indirect solid intercommunication, meaning that solid can move between stations in the network.

[0318] A reaction mixture may be manually transferred from a first station to a second station by a human user. That is, the first station may also be in indirect material intercommunication with the second station via a human user by taking a reaction mixture out of the first station

[0319] 008773897 and transferring it into the second station. Thus, a reaction mixture provided within a station may be directly accessible to a human user.

[0320] Accordingly, the platform may further comprise one or more external stations, wherein each external station is not in direct material intercommunication with the network of the stations, and wherein each external station comprises an external substation, wherein each external substation of a first external station is for executing a different synthetic operation on the reaction mixture relative to each substation of each station. The external station may be any one of the types of stations as described herein.

[0321] In one arrangement of the network, each station is connected in a linear series, such that a second station is in direct intercommunication with a first station and a third station, and the first station is in indirect intercommunication with a third station via the second station, yet the first station may not be in direct intercommunication with the third station (see Figure 1).

[0322] In an alternative arrangement of the network, each station is connected in an array, in contrast to a linear series, such that a station is in direct intercommunication with each of the other stations in a many-to-many relationship (see Figure 2).

[0323] The chemical processing platform of the present invention can carry out the methods of the present invention. At least one substation, such as each substation, in the chemical processing platform can execute a synthetic operation on a reaction mixture.

[0324] A substation of a first station is for executing a different synthetic operation on the reaction mixture relative to each substation in a second station. A substation of a first station is therefore different to a substation of a second station in the network. Each station is overall configured to perform a discrete task relative to a different station.

[0325] The substation of each station is for executing a synthetic operation on a first reaction mixture to obtain a second reaction mixture. For most operations, the synthetic operation causes the first reaction mixture to be different from the second reaction mixture.

[0326] Alternatively, the synthetic operation causes the first reaction mixture to be identical to the second reaction mixture.

[0327] As an example, a chemical processing platform may comprise a first station and a second section, wherein the first station comprises a substation which is for executing a purification of the reaction mixture, and the second station comprises a substation which is for executing an analysis of the reaction mixture.

[0328] Preferably, one station, such as each station, comprises a first substation and a second substation, wherein the first and second substation are for executing the same synthetic operation on the reaction mixture, and are in material intercommunication with another

[0329] 008773897 station, such as a substation of another station. It follows that in some embodiments, a station may comprise a plurality of substations which are each for executing the same synthetic operation. When a plurality of substations within the same station are each for executing the same synthetic operation on the same first reaction mixture, it is generally expected that each substation yields the same second reaction mixture.

[0330] By providing a plurality of substations within a station which is each for executing the same synthetic operation, the synthetic operations may be performed more rapidly. This also provides a plurality of substations which can serve as a back-up in the case where a single substation becomes faulty.

[0331] Alternatively, one station, such as each station, comprises a first substation and a third substation, wherein the first and third substation are for executing a different synthetic operation on the reaction mixture, and are in material intercommunication with another station, such as a substation of another station. When a plurality of substations within the same station which are each for executing a different synthetic operation on the same first reaction mixture, each substation may yield either the same second reaction mixture, or a different second reaction mixture.

[0332] By providing a plurality of substations within a station in which two substations are each for executing a different synthetic operation, there is provided greater flexibility in the synthetic operations.

[0333] Preferably, the network of stations has a first station and a second station, and the second station comprises a substation which is dependently for executing a synthetic operation on the reaction mixture based on a synthetic operation for executing at a substation of the first station. The substation of the second station may therefore be adjusted depending on the synthetic operation performed prior by a substation in the first station.

[0334] The first station may comprise a substation of the first station which is dependently for executing a synthetic operation on the reaction mixture based on a synthetic operation to be performed at a substation of the second station. The substation of the first station may therefore be adjusted depending on the synthetic operation to be performed in a substation of the second station.

[0335] Synthetic operations may be performed within each station in parallel. For example, operations may be performed in each synthesis station in parallel, or within a purification station in parallel, or within an analysis station in parallel.

[0336] Suitably, the chemical processing platform is for performing synthetic operations for chemical discovery and scale-up, and each substation may be sized appropriately. The

[0337] 008773897 chemical processing platform is typically used for laboratory-scale synthesis. Such synthetic scales may correspond to a reaction mixture having a mass of between 0.1 mg to 1 kg.

[0338] In some cases, the reaction mixture may have a mass of less than 1 kg, such as less than 100 g, such as less than 10 g, such as less than 1g.

[0339] In some cases, the reaction mixture may have a mass of more than 0.1 mg, such as more than 1 mg, such as more than 10 mg, such as more than 100 mg.

[0340] In some cases, the reaction mixture may have a mass of between 0.1 mg to 1 kg, such as 1 mg to 100 g, such as 10 mg to 10 g, such as 100 mg to 1 g.

[0341] The present invention also provides a plurality of chemical processing platforms that are in signalling communication, wherein at least two chemical processing platforms, such as each chemical processing platform, in the system are remotely located from each other. The plurality of chemical processing platforms may be in signalling communication via a cloudbased system.

[0342] The chemical processing platform of the present invention preferably comprises at least one of the following specific examples of stations and substations, such as a synthesis station and a synthesis substation, a purification station and a purification substation, and an analysis station and an analysis substation, as described further below.

[0343] Operation Data Collection Unit

[0344] The chemical processing platform also comprises an operation data collection unit. The operation data collection unit is for collecting operation data on the synthetic operation performed within the substations. That is, the operation data collection unit is configured to collect operation data about a synthetic operation performed within a substation.

[0345] In some embodiments, the chemical processing platform comprises an operation data collection unit, and the operation data collection unit receives operation data from the stations, such as each of the stations. In this case, the operation data collection unit is in signalling communication with the stations. The stations may include the measurement device(s) needed to collect the operation data, and the operation data is then communicated from the device(s) to the operation data collection unit. Each station may include multiple operation data measurement devices which communicate with an operation data collection unit.

[0346] In some embodiments, the stations comprise an operation data collection unit, and the operation data collection unit receives operation data from the substations, such as each of the substations. In this case, the operation data collection unit is in signalling

[0347] 008773897 communication with the substations. The substations may include the measurement device(s) needed to collect the operation data, and the operation data is then communicated from the measurement device(s) to the operation data collection unit. Each station may include multiple operation data measurement devices which communicate with an operation data collection unit.

[0348] In some embodiments, the substations comprise an operation data collection unit, and the operation data collection unit receives operation data from the substations. In some embodiments, the each of the substations comprise an operation data collection unit, and the operation data collection unit receives operation data from each of the substations. The substations may include the measurement device(s) needed to collect the operation data, and the operation data is then communicated to the operation data collection unit of the substation. Each substation may include multiple operation data measurement devices which communicate with an operation data collection unit.

[0349] The signalling communication between the operation data collection unit and any measurement devices may be via any suitable means, such as electronic communication or optical communication. The measurement device(s) and operation data collection unit may use an ethernet connection, such as power over ethernet connection.

[0350] Alternatively, the operation data collection unit may collect the operation data itself within the substation. In this case, the operation data collection unit may comprise one or more operation data measurement devices. Each operation data collection unit may include multiple operation data measurement devices which communicate within the operation data collection unit.

[0351] The operation data may be collected using any suitable means, such as a device for collecting operation data, as described herein. An operation data measurement device may be any device suitable for measuring analytical data obtainable from a synthetic operation, such as a synthesis, purification or analysis step.

[0352] The operation data measurement device may be a temperature probe, pressure probe, flow meter, colorimeter, camera, UV-Vis spectrometer, mass spectrometer, an IR spectrometer, a hyperspectral imaging spectrometer, a Raman spectrometer, an X-ray spectrometer, an NMR spectrometer. The operation data measurement device is typically a temperature probe, pressure probe, flow meter, colorimeter, or camera.

[0353] The operation data may be collected using any suitable means, such as a temperature probe, pressure probe, flow meter, colorimeter, camera, UV-Vis spectrometer, mass spectrometer, an IR spectrometer, a hyperspectral imaging spectrometer, a Raman spectrometer, an X-ray spectrometer, an NMR spectrometer.

[0354] 008773897 The operation data collection unit is also in signalling communication with the control unit.

[0355] Control Unit

[0356] The chemical processing platform also comprises a control unit. The control unit is configured to receive operation data and to generate instruction sets from a synthetic procedure and / or the operation data for synthetic operations.

[0357] The control unit is in signalling communication with the two or more stations and the operation data collection unit. That is, the control unit is in signalling communication with the two or more stations and the operation data collection unit. The signalling communication between the control unit and operation data collection unit may be via any suitable means, such as electronic communication or optical communication. The control unit and operation data collection unit may use an ethernet connection, such as power over ethernet connection.

[0358] The control unit is for receiving operation data from the operation data collection unit. That is, the control unit is configured to receive operation data from the operation data collection unit. The control unit typically receives operation data from the operation data collection unit. The operation data collection unit may provide ‘raw’ operation data to the control unit. In addition or alternatively, the operation data collection unit may provide processed operation data to the control unit. The operation data may be provided to the control unit during a synthetic operation, such as continuously through a synthetic operation. Alternatively, the operation data may be provided to the control unit at the end of a synthetic operation.

[0359] The control unit is for generating an instruction set based on the synthetic procedure and the operation data, and providing the substation with the instruction set for execution of the synthetic operation. That is, the control unit is configured to generate an instruction set based on the synthetic procedure and the operation data, and provide the substation with the instruction set for execution of the synthetic operation. The control unit generates the instruction set based on the method described herein.

[0360] The control unit provides the substation with the instruction set for execution of the synthetic operation.

[0361] In some embodiments, the control unit provides a machine-readable instruction set to the substation. In this case, the instruction set can be interpreted by the substation, and the substation can act upon that instruction set to perform the synthetic operation as defined in the instruction set. This may allow for the autonomous execution of the synthetic operation based on the instruction set.

[0362] 008773897 In some embodiments, the control unit provides a human-readable instruction set to the substation. In this case, the instruction set can be interpreted by the user operating the substation, and the user can act upon that instruction set to perform the synthetic operation as defined in the instruction set.

[0363] The instructions set may be provided on a user interface. In some embodiments, the chemical processing platform further comprises a user interface. The user interface may display information about the instruction set used for the synthetic operation being performed.

[0364] Each station, or each substation may comprise a user interface. Alternatively, a user interface may be provided by a software platform for use on a portable device (e.g., a computer, tablet, smartphone or VR headset). The user interface is typically in communication with the controller. The user may carry out the synthetic operation according to the instruction set provided on the user interface, using the substation.

[0365] In some embodiments, the control unit provides a machine-readable and a human-readable instruction set to the substation. In this way, the instruction set can be performed semi- autonomously, with oversight from a user. This allows the instruction set to be executed autonomously on the station, executed manually on the station by a human user, or using a mix of autonomous and human execution.

[0366] Synthesis Station and Synthesis Substation

[0367] In some embodiments, the two or more stations of the chemical processing platform comprise a synthesis station comprising one or more synthesis substations for executing a synthesis of a reaction mixture.

[0368] The synthesis station comprises one or more synthesis substations, wherein the synthesis substation is for executing a synthesis operation on a reaction mixture. Typically, the synthesis of the reaction mixture includes a set-up step, a reaction step, and a quench step. The set-up step may comprise setting up a reaction, such as introducing reagents and adjusting reaction conditions. The reaction step may comprise performing a reaction. The quench step may comprise terminating a reaction.

[0369] The synthesis substation includes a reaction vessel for the performance of a reaction within. The reaction vessel is not particularly limited, and it may be chosen with the intended reaction in mind.

[0370] The reaction vessel is suitable for use as the synthesis substation within a chemical processing platform, and is suitable for use with a fluid and solid transfer apparatus, where such apparatus is for the delivery of reagents, catalysts and solvents into the reaction

[0371] 008773897 vessel, as well as the removal of materials from the reaction vessel, for example after reaction completion.

[0372] The reaction vessel may be, for example, a reaction flask, such as a round-bottomed flask, a reaction cartridge, a vial, or a flow reactor, amongst other reactors. However, the present inventors have realised that the use of custom reactors tailored towards the relevant reactions may reduce the size, cost and complexity of reaction setups. Specific embodiments of reactors are described herein.

[0373] In one embodiment, the reactor is a glass reactor with built-in electrode holders and electrical connection ports accommodating a range of electrodes for general electrochemistry.

[0374] In one embodiment, the reactor comprises integrated pneumatic connections for inert or reactive gas purposes. This eliminates the need for glass joint adaptors to route pneumatic tubing into the reactor and improving repeatability and accuracy of gas inlet / outlet positioning within the reactor.

[0375] In one embodiment, the reactor comprises integrated sampling ports at different positions within the reactor. This enables accurate monitoring of reaction progress and uniformity throughout the mixture.

[0376] In one embodiment, the reactor comprises integrated UV lamps or LEDs, as a single source or a distributed array placed to ensure equal exposure throughout the reaction mixture, with wavelength, intensity, and timing controls and feedback to facilitate diverse photochemistry reactions.

[0377] In one embodiment, the reactor comprises a modular plug-and-play mechanism directly integrated into the wider fluid handling aspects of the chemical processing platform. This reduces tubing lengths and provides a more compact system design.

[0378] In one embodiment, the reactor is a smart reactor with integrated reaction monitoring feeding into the wider control and data ingestion architecture.

[0379] In one embodiment, the reactor comprises integrated, changeable selectively permeable membranes which enables the continuous removal of product or by-products from the reaction. This facilitates higher yields or increased reaction speed.

[0380] In one embodiment, the reactor is a high-pressure reactor with integrated pressure and temperature control for gas-liquid reaction.

[0381] 008773897 In one embodiment, the reactor is a multi-module reactor with connected chambers and transport mechanisms for multi-step reactions with minimal transit of intermediates.

[0382] In one embodiment, the reactor comprises an integrated microwave irradiation and temperature feedback for rapid, uniform, and accurate heating of reaction mixtures. This reduces overall reaction time.

[0383] The synthesis substation may be provided with a means for transferring the contents of one present reaction to another synthesis substation. For example, a synthesis substation may be provided with computer-controlled syringe pumps and distribution valves for the delivery of fluids into a reaction vessel, and a synthesis substation may be provided with a computer- controlled syringe pump for removal of material from a reaction vessel, for example, to ready the reaction vessel for use in a further reaction.

[0384] Where the chemical processing platform comprises a synthesis substation, the synthesis substation may comprise a sensor for monitoring a work-up process. The sensor may comprise a conductivity sensor and an image-based sensor. The image-based sensor may comprise a camera for recording still or video images. The synthesis substation may comprise an analysis substation which is built therein. Such devices may permit real-time monitoring of the reaction within the synthesis substation, and are described further herein.

[0385] The synthesis station may be provided in thermal communication with a centralised refrigeration system, which is configured to modulate the temperature of a reaction mixture within a synthesis station or a synthesis substation. Variable temperatures across multiple synthesis substations with a synthesis station may be achieved simultaneously by modulating the flow rate in a digital manner using pulse width modulation or set point and hysteresis to start or stop the flow through each reactor, or in an analogue manner by throttling the flow through each reactor with a proportional valve or other means. The centralised refrigeration system may comprise second hot-fluid loop or electric heating rods, which may be embedded in the housing of the centralised refrigeration system to achieve elevated temperatures.

[0386] In some use cases, the first substation is a synthesis substation. Where the first substation is a synthesis substation, the second substation may be a purification substation, as described further herein.

[0387] Purification Station and Purification Substation

[0388] In some embodiments, the two or more stations of the chemical processing platform comprise a purification station comprising one or more purification substations for executing a purification of a reaction mixture.

[0389] 008773897 The purification station comprises one or more purification substations, wherein the purification substation is for executing purification of a reaction mixture. The purification may include, but is not limited to, the steps of work-up and evaporation and purification. Thus, the purification station may be configured to provide a means for working-up a reaction, a means for evaporating solvent from the reaction, and a means for purifying the mixture to isolate the desired product.

[0390] A plurality of consecutive purification steps may be performed on the purification station or the purification substation, such as two or more consecutive purification steps, such as three or more consecutive purification steps, such as four or more consecutive purification steps. Multiple purifications may be needed to obtain a reaction product having a predetermined minimum yield and a predetermined minimum purity.

[0391] In some use cases, the first substation is a purification substation. Where the first substation is a purification substation, the second substation may be an analysis substation, as described further herein.

[0392] Each purification substation may comprise a system of syringe pumps connected to different distribution valves to allow fluid movement from any vessel into a separator vessel.

[0393] The separator vessel may be a pear-shaped glass container with an adaptor at the bottom to allow the integration of fluidic / hydraulic connections. The separator vessel may further contain an adaptor for filtration to avoid clogging lines with possible solids formed during the separation procedure.

[0394] The purification substation may comprise an overhead stirrer to mix the contents of the vessel at a specified speed for a determined amount of time.

[0395] The purification substation may further comprise an impeller which may be connected to the overhead stirrer. Preferably, the impeller has a geometry which maximises axial or vertical mixing so as to increase the liquid / impeller contact. By changing the geometry of the impeller, it can be useful to improve the efficiency of mixing for separation and extraction processes.

[0396] The purification substation may further comprise a sensor configured to monitor a work-up process. The nature of the sensor in the purification substation may be dictated by the synthetic operation to be performed, such as the reaction performed in the synthesis substation, and the reaction product, as well as the reaction parameters that are under consideration.

[0397] In addition, the sensor may be able to detect phase boundaries in a biphasic reaction mixture. Where a phase boundary is expected in a biphasic reaction mixture, by is not

[0398] 008773897 detected by the sensor, the purification station may take action to form the phase boundary. For example, the purification station may add additional solvent to the reaction mixture to create a biphasic reaction mixture with a clear phase boundary. This may aid separation and washing of the reaction mixture.

[0399] In addition, the sensor may comprise a pH sensor. The pH sensor may monitor the pH of the reaction mixture. Where the pH of the reaction mixture is not as expected, the purification station may add a suitable acid or base to correct the pH of the reaction mixture to within a desired range.

[0400] Preferably, the sensor of the purification substation includes a conductivity sensor or an image-based sensor, or both.

[0401] The conductivity sensor may be composed of a series of1 / 4-28” fittings adaptors along with a stainless steel 304 metal tube of variable length to measure the conductivity between two different points of the flowing solution. The separation method is based on a moving average algorithm to detect the change in conductivity of the sensor. The process may be to sample 1 mL of the solution from the separator vessel, measure the conductivity of the solution, compare the conductivity value with the previous values, determine if there is a change in the phase based on the change in the conductivity, stop taking 1 mL, and transfer the desired phase to the product vessel.

[0402] The conductivity sensor may alternatively be composed of a series of1 / 4-28” fittings adaptors along with a stainless steel 316L metal tube of variable length to measure the conductivity between two different points of the flowing solution. The separation method is based on a moving average algorithm to detect the change in conductivity of the sensor. The process may be to extract in a continuous fashion a full stroke of the syringe size from the separator vessel, while measuring the conductivity of the solution passing by the stainless steel 316L metal tube, compare the conductivity value with the previous values, determine if there is a change in the phase based on the change in the conductivity, stop the syringe pump movement, and transfer the desired phase to the product vessel.

[0403] The image-based sensor may comprise a camera and an identification code. The imagebased sensor may be particularly useful for solutions having different phases which do not completely separate after mixing and may, for example, form emulsions.

[0404] The camera is typically suitable for recording images in real time, and is typically capable of recording images in colour, grayscale and black and white.

[0405] The identification code can be used to calibrate the region of interest within the separator vessel. The identification code may be located on the surface of the separation vessel, or

[0406] 008773897 any surface which is accessible from the camera. An example of an identification code may be a QR code.

[0407] Preferably, the purification substation comprises a conductivity sensor and an image-based sensor.

[0408] The purification substation may further comprise an evaporator, such as a rotary evaporator, which may permit removal of the gathering solvent during an evaporation process, and a product flask for holding a reaction mixture comprising a solvent which is intended to be evaporated. Preferably, the evaporator comprises a sensor configured to detect the rate of solvent evaporation in real-time.

[0409] Preferably, the product flask has high internal surface area meshes which can increase the speed and effectiveness of an evaporation process. A dried solid product may be redissolved and removed via a pump. This is in contrast to a flask having a smooth surface, such as a smooth piece of glassware, which requires a wide opening on rotary evaporators as a human user will need to manually remove solid products through the opening.

[0410] Analysis Station and Analysis Substation

[0411] In some embodiments, the two or more stations of the chemical processing platform comprises an analysis station comprising one or more analysis substations for executing an analysis of a reaction mixture.

[0412] The analysis station comprises one or more analysis substations, wherein the analysis substation is for analysis of a reaction mixture. Preferably, the analysis station comprises one or more analysis substations, wherein a first analysis substation and a second analysis substation are the same, or wherein a first analysis substation is different to a second analysis substation.

[0413] The analysis substation collects and records analytical data, such as measuring a chemical or physical property, of a chemical or biological reaction, such as a reagent, intermediate or product thereof.

[0414] The analysis data collected by the one or more analysis substations is transmitted to the network for analysis.

[0415] It is particularly preferred that the analysis station is provided with multiple analysis substations for measuring different characteristics of the chemical or biological reaction. Such a configuration may allow the platform to define a reaction outcome more accurately, as it may also allow the platform to analyse the reaction and the reaction products more

[0416] 008773897 thoroughly, with a greater opportunity to identify a change in reaction outcome with a change in a chemical and / or physical input.

[0417] The analysis substation may be used to measure a chemical property, and may suitably be selected from a mass spectrometer, an IR spectrometer, a hyperspectral imaging spectrometer, a Raman spectrometer, an X-ray spectrometer, an NMR spectrometer. The mass spectrometer may be selected from a quadrupole MS, a TOF-MS, an ion trap MS, an orbitrap MS, an LC-MS, an FT-ICR MS, a MALDI-TOF and an ESI-MS. The NMR spectrometer may be used to perform1H NMR spectrometry or13C NMR spectrometry.

[0418] The analysis substation may also be used to measure a physical property of a reaction mixture. For example, the analysis substation may comprise a means for measuring acoustics, a means for measuring opacity, a means for measuring viscosity or a means for measuring temperature.

[0419] An analysis unit may be used in combination with a chromatographic unit for the at least partial separation of reaction components for analysis, such as an LPLC unit, an HPLC unit, a LIPLC unit, or a GC unit.

[0420] As noted herein, the analysis substation may also be built into a synthesis substation to analyse a chemical or biological reaction in the synthesis substation. Thus, real-time chemical or physical property analysis of the reaction mixture during the duration of the synthesis step may be performed. Analysis of the reaction mixture may inform whether or not real-time adjustment is required for the synthetic operation performed by the synthesis substation. Analysis includes any one of the above analytical techniques

[0421] For example, upon obtaining a second reaction mixture from a first reaction mixture by performing a first synthetic operation, the second synthetic operation may involve adjusting a characteristic of the reaction mixture to within a predetermined range. The characteristic of the reaction mixture may be temperature and pH.

[0422] The chemical processing platform may comprise additional components which assist in the performance of synthetic operations.

[0423] The chemical processing platform may further comprise a system of pipes, controlled via a system of pumps and valves, to provide direct material intercommunication with the stations, and substations, in the network. The control of the system of pumps and valves may be performed autonomously by the chemical processing platform.

[0424] The chemical processing platform may further comprise an interchanging means configured to switch out substations of the same type within the network. An example of such an interchanging means is a rack mounting sliding tray.

[0425] 008773897 The chemical processing platform may further comprise a centralised solvent bank. The centralised solvent bank may be in direct and / or indirect fluid communication with each station in the network, and may be configured to permit a solvent to flow therethrough. The centralised solvent bank may send solvent to a station, such as a synthesis station, which requires a solvent to perform a chemical or biological reaction. In some cases, the centralised solvent bank is configured to receive solvent for storage, such as solvent extracted from a purification station after an evaporation step. The centralised solvent bank may further comprise a plurality of individual solvent banks, wherein a first individual solvent bank and a second individual solvent bank each comprise a different solvent. The solvents which may be contained in the solvent banks are not particularly limited, and may be chosen depending on the reaction to be performed, and the reagents and products which may be involved.

[0426] A centralised solvent bank which is in fluid communication with each station is particularly useful when each station in the network comprises a plurality of configurations such that multiple parallel operations on the reaction mixtures are performed concurrently across the chemical processing platform. Access to a centralised solvent bank allows for one copy of each solvent to service these multiple parallel operations.

[0427] The chemical processing platform may further comprise a monitoring system for overseeing the performance of the chemical processing platform and for providing a visualisation of the operations performed by and operation data, as described herein, generated from and collected by the chemical processing platform via the control unit. The visualisation may include timestamps of synthetic operations, such as the time at which a particular substation performs a synthetic operation and the status of a particular substation.

[0428] Other Preferences

[0429] Each and every compatible combination of the embodiments described above is explicitly disclosed herein, as if each and every combination was individually and explicitly recited.

[0430] Various further aspects and embodiments of the present invention will be apparent to those skilled in the art in view of the present disclosure.

[0431] “and / or” where used herein is to be taken as specific disclosure of each of the two specified features or components with or without the other. For example “A and / or B” is to be taken as specific disclosure of each of (i) A, (ii) B and (iii) A and B, just as if each is set out individually herein.

[0432] 008773897 Unless context dictates otherwise, the descriptions and definitions of the features set out above are not limited to any particular aspect or embodiment of the invention and apply equally to all aspects and embodiments which are described.

[0433] Certain aspects and embodiments of the invention will now be illustrated by way of example and with reference to the figures described above.

[0434] Experimental and Results

[0435] The following examples are provided solely to illustrate the present invention and are not intended to limit the scope of the invention, as described herein.

[0436] General Experimental Remarks

[0437] All NMR measurements were recorded on Bruker Avance III HD 600 spectrometer operating at 600, 151 and 565 MHz for1H,13C and19F, respectively, or Bruker Avance III 400 spectrometer operating at 400 and 100 MHz for1H and13C respectively. Unless otherwise noted, the samples for NMR experiments were prepared in CDCI3. Spectra were collected at 298 K, and chemical shifts are reported in ppm relative to TMS or residual solvent (for1H NMR: CDCI3 = 6 7.26 ppm, CD3CN = 5 1.94 ppm, CD3OD = 5 3.31 ppm, DMSO-cfe = 6 2.50 ppm; for13C NMR: CDCI3 = 6 77.16 ppm, CD3CN = 5 1.32, 118.26 ppm, CD3OD = 5 49.00 ppm, DMSO-cfe = 5 39.52 ppm). Multiplicities are given as s: singlet, d: doublet, t: triplet, q: quartet, m: multiplet, br s: broad singlet with coupling constants reported in Hz. The spectra were processed with the Bruker Topspin 3.5 software package. High resolution mass spectra were obtained on a Bruker maXis LC / MS.

[0438] HPLC analysis was performed on a Thermo Dionex Ultimate 3000 equipped with a LPG-3400 RS pump, a WPS-3000TRS autosampler, a TCC-3000SD column compartment and a DAD-3000 diode array detector. A C18 HPLC column was used. The solvent system is hexane in acetonitrile', with a base.

[0439] Example 1: 1-[5-(1-piperidyl)pyrazin-2-yl]ethan-1-one

[0440] Scheme 1 : Preparation of 1-[5-(1-piperidyl)pyrazin-2-yl]ethan-1-one from 1-(5- chloropyrazin-2-yl)ethan-1-one and piperidine.

[0441] 008773897 As an exemplary example, an embodiment of the chemical processing platform was used to perform the above reaction according to the methods of the invention.

[0442] This workflow generates two different files that are used for an automated synthesis:

[0443] 1. .xdl file: A universal synthesis language file containing all the necessary steps for the synthesis, independent from the platform used.

[0444] 2. .json: A platform specific executable file containing all the base steps that can be directly executed in the portable platform.

[0445] The synthetic procedure was provided as input data into the chemical processing platform by a human user (see Figure 5). The reaction mixture was put through the chemical processing platform and all synthetic steps were executed in sequence using machine-readable instruction sets generated by the control unit. The generated XDL file is shown in Annex 1. The prose description of each procedure performed by each (sub)station is shown below.

[0446] (1) SRQ Procedure Description

[0447] 1. Ensure any hardware used for chemical handling is clean.

[0448] - Clean with solvent 'N,N-dimethylformamide' and use gas 'nitrogen' to aid drying.

[0449] - Repeat '3' times.

[0450] 2. Evacuate the headspace of 'reactor', by applying vacuum (for '1.0 min') and refilling with 'nitrogen' (for '1.0 min'). Repeat '2' times.

[0451] 3. Add '1.0 eq', into 'reactor' from '1-(5-chloropyrazin-2-yl)ethan-1-one'. Use a minimal amount of 'N,N-dimethylformamide' to rinse if necessary.

[0452] - Control the conditions of 'reactor' by stirring at '400 RPM'.

[0453] 4. Add '20.0 mL', into 'reactor' from 'N,N-dimethylformamide',

[0454] - at rate '10.0 mL / min'. Use a minimal amount of 'N,N-dimethylformamide' to rinse if necessary.

[0455] - Control the conditions of 'reactor' by stirring at '400 RPM'.

[0456] 5. Add '1.4 eq', into 'reactor' from 'piperidine'. Use a minimal amount of 'N,N- dimethylformamide' to rinse if necessary.

[0457] - Control the conditions of 'reactor' by stirring at '400 RPM'.

[0458] 6. Add '2.0 eq', into 'reactor' from 'N-ethyl-N-isopropylpropan-2-amine'. Use a minimal amount of 'N,N-dimethylformamide' to rinse if necessary.

[0459] - Control the conditions of 'reactor' by stirring at '400 RPM'.

[0460] 7. Heat 'reactor' contents to '22.0 °C for '4.0 h', whilst stirring at '400 RPM'.

[0461] 8. Add '100.0 mL', into 'reactor' from 'ethyl acetate',

[0462] - at rate '10.0 mL / min'. Use a minimal amount of 'ethyl acetate' to rinse if necessary.

[0463] - Control the conditions of 'reactor' by stirring at '400 RPM'.

[0464] 9. Transfer '130.0 mL', from 'reactor' to 'product_flask',

[0465] - at rate '20.0 mL / min'.

[0466] 008773897 - Control the conditions of 'reactor' by stirring at '400 RPM'.

[0467] 10. Ensure any hardware used for chemical handling is clean.

[0468] - Clean with solvent 'ethyl acetate' and use gas 'nitrogen' to aid drying.

[0469] - Repeat '3' times.

[0470] (2) Washing Procedure

[0471] 1. Wash contents of 'crude_1' with '10% sodium chloride (aq)', 3 times.

[0472] - Transfer washed product (top phase) to 'product_1' and discard bottom phase to 'waste_1', following the final wash.

[0473] (3) Evaporation Procedure

[0474] 1. Evaporate contents of 'rotavap' under vacuum ('140.0 mbar') for '6.67 min'.

[0475] - Set heating bath temperature to '40.0 °C, condenser temperature to '5.0 °C and stirring speed to '150 RPM'.

[0476] 2. Transfer '75.0 mL', from 'rotavap' to 'waste_1',

[0477] - at rate '60.0 mL / min'.

[0478] 3. Evaporate contents of 'rotavap' under vacuum ('140.0 mbar') for '6.67 min'.

[0479] - Set heating bath temperature to '40.0 °C, condenser temperature to '5.0 °C and stirring speed to '150 RPM'.

[0480] 4. Transfer '75.0 mL', from 'rotavap' to 'waste_1',

[0481] - at rate '60.0 mL / min'.

[0482] 5. Evaporate contents of 'rotavap' under vacuum ('20.0 mbar') for '20.0 min'.

[0483] - Set heating bath temperature to '40.0 °C, condenser temperature to '5.0 °C and stirring speed to '150 RPM'.

[0484] 6. Transfer '50.0 mL', from 'rotavap' to 'waste_1',

[0485] - at rate '60.0 mL / min'.

[0486] (4) Analysis Procedure - NMR

[0487] 1. Analyse the contents of 'sample_flask' via NMR ('1 H').

[0488] 2. Analyse the contents of 'sample_flask' via NMR (' 13C).

[0489] (5) Analysis Procedure - LCMS

[0490] 1. Analyse the contents of 'sample_flask' via LCMS ('ESI', 'positive' mode). The required solvent system is 'analytical hexane' (weak component) in 'analytical acetonitrile' (strong component), with additive of (basic additive).

[0491] (6) Purification Procedure - PrepH PLC

[0492] 008773897 1. Purify the contents of 'sample_flask' via PrepHPLC ('C18' column). The required solvent system is 'analytical hexane' (weak component) in 'analytical acetonitrile' (strong component), with additive of (basic additive).

[0493] (7) Analysis Procedure - NMR

[0494] 1. Analyse the contents of 'sample_flask' via NMR ('1 H').

[0495] 2. Analyse the contents of 'sample_flask' via NMR (' 13C).

[0496] (8) Analysis Procedure - LCMS

[0497] 1. Analyse the contents of 'sample_flask' via LCMS ('ESI', 'positive' mode). The required solvent system is 'analytical hexane' (weak component) in 'analytical acetonitrile' (strong component), with additive of (basic additive).

[0498] Discussion of Results

[0499] Example 1 describes the preparation of 1-[5-(1-piperidyl)pyrazin-2-yl]ethan-1-one from 1-(5- chloropyrazin-2-yl)ethan-1-one and piperidine using the chemical processing platform and methods of the invention.

[0500] The visualisation of the preparation of 1-[5-(1-piperidyl)pyrazin-2-yl]ethan-1-one from 1-(5- chloropyrazin-2-yl)ethan-1-one and piperidine was obtained using the monitoring system, in the form of a lifecycle plot, of the chemical processing platform (see Figure 9). The abbreviations on the y-axis of the visualisation correspond to various substations of the network in which compilation occurred, and are given as follows: ILC: Inventory, Label, COSHH; RMC: Raw Materials Commissioning; SRQ: Setup, Reaction and Quenching; W: Work-up; E: Evaporation; P: Purification; A: Analysis (on NMR and UPLC). Timestamps are provided at the start of an automated operation at each substation, and the reaction mixture was monitored according to the visual line across the lifecycle plot. For clarity, the lifecycle plot (Figure 9) does not show all analysis and purification cycles, where the reaction mixture is analysed during purification. This is represented by the ongoing purification and analysis. Annex 1 shows the generated XDL file for each synthetic operation performed.

[0501] Prior to performing any synthetic operations, the reaction mixture underwent a series of preparation steps: an ILC step to prepare the synthetic procedure and to produce COSHH labels, and an RMC step for raw materials commissioning.

[0502] The synthetic procedure was provided by the human user and used by the chemical processing platform to prepare a machine-readable instruction set for a first synthetic operation using the control unit. The first synthetic operation was a synthesis step performed overnight at a synthesis substation. While the synthesis step was being

[0503] 008773897 performed within the synthesis substation, operation data within the synthesis substation was being collected by the operation data collection unit.

[0504] Upon completion of the initial synthesis step and quenching of the resulting reaction mixture, the control unit uses both the synthetic procedure and the operation data from the synthesis step to generate a machine-readable instruction set for a further synthetic operation. The further synthetic operation was dependent on the operation data collected after the synthesis step and the synthetic procedure initially provided. Here, further synthetic operations were a series of washing, evaporation and purification in a purification substation.

[0505] Based on the operation data collected during the purification steps and the initial synthetic procedure, the last synthetic operations were a series of analysis in an analysis substation (1H NMR spectrometer and13C NMR spectrometer). The UPLC trace (see Figure 6),1H NMR spectrum (see Figure 7) and13C NMR spectra (see Figure 8) of the final reaction product each confirm the identity of the final reaction product as 1-[5-(1-piperidyl)pyrazin-2-yl]ethan-1-one.

[0506] Upon completion of the synthetic operations, the combined operation data collected across each synthetic operation was aggregated to produce a library of operation data. The library of operation data may then be used in a repeat preparation of 1-[5-(1-piperidyl)pyrazin-2- yl]ethan-1-one from 1-(5-chloropyrazin-2-yl)ethan-1-one and piperidine for discovery of alternative routes and / or to optimise efficiency and yield of the target product.

[0507] 008773897 Annex 1 (XDL and JSON Code) the headspace of 'reactor' , by applying vacuum (for '1.0 min' ) and refilling with 'nitrogen' (for

[0508] Generated XDL for Setup, Reaction, '1.0 min ' ) . Repeat ' 2 ' times . " Quench }, "steps" : [ {

[0509] { "details " : { "id" : "bl46de56-9a82-37a4-963c- "name": "Repeat", 6d7546d9d33d" , "repeats" : 2,

[0510] "name": "l_SRQ0vl_1099-5-MR- "description" : Cl_Executable" , "Repeat '2 ' times:"

[0511] "xdl_name": "1099-5-MR-C1", }, "graph" : "steps" : [

[0512] "SRQ_001_triconts_V4. j son" , { "chempiler_version" : "curie- "id": "616d5661- chemify-2.10.9", 6d56- 6c75-576e-4c62666b5259 " , "XDL_standard_version" : "3.6.0", "name" : "procedure" : { "ApplyVacuum" , "details " : { "description" : "Apply vacuum ( '0.01 bar' ) to

[0513] }, 'reactor' for '1.0 min' .",

[0514] "steps" : [ "operations " : {

[0515] { "actions " : [

[0516] "id": "6c676c48-6467-646e- 6257-6b4f4f 76704c" , "VacuumOperationType . START" ,

[0517] "name": "ResetHandling" , "description": "Ensure any "SynchronizationOperationType . STAR hardware used for chemical T", handling is clean . \nClean with solvent ' N, N-dimethyl formamide ' "SynchronizationOperationType . GET_ and use gas 'nitrogen' to aid TIME", drying . \nRepeat '3' times.", "operations " : { "SynchronizationOperationType . STOP "actions " : [

[0518] "ChemicalHandlingOperationType . RES "VacuumOperationType . STOP" ET" ] ,

[0519] ] , "parameters " : [ "parameters " : [ {

[0520] { "actioner " :

[0521] "actioner" : "pneumatic_controller " , "backbone" ,

[0522] "cleaning_solvent" : "input_value" : 0.01, "solvent_3", "target" :

[0523] " f lushing_gas " : "reactor" "passive_manifold" , }, "cleaning_repeats " : { 3, "actioner" :

[0524] " f lushing_repeats " : "timer" , 1

[0525] } "input_value" : 1

[0526] ] },

[0527] } {

[0528] }, "actioner" :

[0529] { "timer" ,

[0530] "details " : { "name" : "target_value" : 1

[0531] "EvacuateAndRef ill " , }, "repeats" : 1, { "description": "Evacuate "actioner" :

[0532] 008773897 "timer" {

[0533] }, "actioner" : { "pneumatic_cont roller " "actioner" : } "pneumatic_cont roller " ]

[0534] } } ] } } ] }, } { ]

[0535] "id": "47414170- }, 6c73-7041-5473-745774556d5a " , { "name" : "details " : {

[0536] "ApplyGas " , "name" : "description" : "AddWithConditionsControl " , "Apply 'nitrogen' (at '5.0 "repeats" : 1, mL / min' ) to 'reactor' for '1.0 "description": "Add '1.0 min ' . " , eq' , into 'reactor' from 'l- (5- "operations " : { chloropyra zin-2 -yl ) e than- 1- one ' . "actions " : [ Use a minimal amount of 'N,N- dimethyl formamide ' to rinse if

[0537] "GasHandlingOperationType . START" , necessary . \nControl the conditions of 'reactor' by stirring at '400

[0538] "SynchronizationOperationType . STAR RPM' . " T", },

[0539] "steps" : [

[0540] "SynchronizationOperationType . GET_ { TIME", "id": "6174696f-6774- 6761- 6658- 6f 6254794642 " ,

[0541] "SynchronizationOperationType . STOP "name" : "StartAgitation" , "description": "Start

[0542] "GasHandlingOperationType . STOP" agitating contents of 'reactor' at

[0543] ] , '400.0 RPM' . ",

[0544] "parameters " : [ "operations " : {

[0545] { "actions " : [

[0546] "actioner" :

[0547] "pneumatic_controller " , "StirringOperationType . START"

[0548] "source" : ] ,

[0549] "passive_manifold" , "parameters " : [

[0550] "target" : {

[0551] "reactor" , "actioner" : "reactor_hotplate" ,

[0552] "input_value" : 0.005 "input_value" :

[0553] }, 400

[0554] { }

[0555] "actioner" : ]

[0556] "timer" , }

[0557] },

[0558] "input_value" : 1 {

[0559] }, "id": "64414145-766a-

[0560] { 4759-5464-794c4656414c",

[0561] "actioner" : "name": "Add",

[0562] "timer" , "description": "Manual Add required . \nAdd '3.01 g' , into

[0563] "target_value" : 1 'reactor' from 'l- (5-

[0564] }, chloropyra zin-2 -yl ) e than- 1- one ' .

[0565] { Use a minimal amount of 'N,N-

[0566] "actioner" : dimethyl formamide ' to rinse if

[0567] "timer" necessary . " ,

[0568] }, "operations " : {

[0569] 008773897 "actions " : [ 6974-7a6d-776678547a74 " , "name" :

[0570] "ChemicalHandlingOperationType . MAN "StartAgitation" , UAL" "description": "Start

[0571] ] , agitating contents of 'reactor' at

[0572] "parameters " : [ '400.0 RPM' . ",

[0573] { "operations " : {

[0574] "actioner " : "actions " : [

[0575] "manual " ,

[0576] "input_value" : { "StirringOperationType . START" "text" : ] ,

[0577] "Manual Add required . \nAdd '3.01 "parameters " : [ g' , into 'reactor' from 'l- (5- { chloropyra zin-2 -yl ) e than- 1- one ' . "actioner" : Use a minimal amount of 'N,N- "reactor_hotplate" , dimethyl formamide ' to rinse if "input_value" : necessary . " 400

[0578] } }

[0579] } ]

[0580] ] }

[0581] } },

[0582] }, {

[0583] { "id": " 6464644 f- 6350-

[0584] "id": "69696174-7469- 596b-7855-4966536c4745 " , 6974-4951-676241564a4e", "name": "Add",

[0585] "name" : "description": "Add "StopAgitation" , '20.0 mL ' , into 'reactor' from

[0586] "description": "Stop ' N, N-dimethyl formamide ' , \nat rate agitating contents of 'reactor' .", '70.0 mL / min' . Use a minimal "operations " : { amount of ' N, N-dimethyl formamide ' "actions " : [ to rinse if necessary.", "operations " : {

[0587] "StirringOperationType . STOP" "actions " : [ ] , "parameters " : [ "ChemicalHandlingOperationType .ADD { !!

[0588] "actioner" : ] , "reactor_hotplate" "parameters " : [ } {

[0589] ] "actioner" :

[0590] } "backbone" ,

[0591] } "source" :

[0592] ] "solvent_3",

[0593] }, "target" :

[0594] { "reactor" ,

[0595] "details " : { "input_value" :

[0596] "name" : 0.02,

[0597] "AddWithConditionsControl " , "rate" : 0.07, "repeats" : 1, "description": "Add "flushing_solvent" : "solvent_3",

[0598] '20.0 mL ' , into 'reactor' from " f lushing_gas " :

[0599] ' N, N-dimethyl formamide ' , \nat rate "pas sive_mani fold" '10.0 mL / min' . Use a minimal } amount of ' N, N-dimethyl formamide ' ] to rinse if necessary . \nControl } the conditions of 'reactor' by }, stirring at '400 RPM' ." {

[0600] }, "id": "6e616969-7474-

[0601] "steps" : [ 7469-5250-4c5379626277",

[0602] { "name" :

[0603] "id": " 69696f 69- 6f 74- "StopAgitation" ,

[0604] 008773897 "description": "Stop rate '10.0 mL / min' . Use a minimal agitating contents of 'reactor' .", amount of ' N, N-dimethyl formamide ' "operations " : { to rinse if necessary.", "actions " : [ "operations " : { "actions " : [

[0605] "StirringOperationType . STOP" ] , "ChemicalHandlingOperationType . MAN "parameters " : [ UAL" { ] ,

[0606] "actioner " : "parameters " : [ "reactor_hotplate" { } "actioner" : ] "manual " ,

[0607] } "input_value" : {

[0608] } "text" :

[0609] ] "Manual Add required . \nAdd '2.66

[0610] }, mL ' , into 'reactor' from

[0611] { ' piperidine ' , \nat rate '10.0

[0612] "details " : { mL / min' . Use a minimal amount of "name" : ' N, N-dimethyl formamide ' to rinse

[0613] "AddWithConditionsControl " , if necessary. " "repeats" : 1, } "description": "Add '1.4 } eq' , into 'reactor' from ] 'piperidine' . Use a minimal amount } of ' N, N-dimethyl formamide ' to }, rinse if necessary . \nControl the { conditions of 'reactor' by "id": "69676f74-6774- stirring at '400 RPM' ." 6974-7768-7451714e6b71",

[0614] }, "name" :

[0615] "steps" : [ "StopAgitation" ,

[0616] { "description": "Stop

[0617] "id": "6f676969-6f69- agitating contents of 'reactor' .", 746e-4463- 6b77796a784e " , "operations " : {

[0618] "name" : "actions " : [ "StartAgitation" , "description": "Start "StirringOperationType . STOP" agitating contents of 'reactor' at ] , '400.0 RPM' . ", "parameters " : [ "operations " : { { "actions " : [ "actioner" : "reactor_hotplate"

[0619] "StirringOperationType . START" } ] , ] "parameters " : [ } { }

[0620] "actioner" : ] "reactor_hotplate" , },

[0621] "input_value" : { 400 "details " : {

[0622] } "name" :

[0623] ] "AddWithConditionsControl " , } "repeats" : 1, }, "description": "Add '2.0 { eq' , into 'reactor' from 'N-ethyl- "id": "64646472-5471- N-isopropylpropan-2-amine ' . Use a 7a69-7368-557449744678", minimal amount of 'N,N- "name": "Add", dimethyl formamide ' to rinse if "description": "Manual necessary . \nControl the conditions Add required . \nAdd '2.66 mL ' , into of 'reactor' by stirring at '400 'reactor' from ' piperidine ' , \nat RPM' . "

[0624] 008773897 }, 7474- 6a61-504675784c55 " ,

[0625] "steps" : [ "name" :

[0626] { "StopAgitation" , "id": "69697474-6169- "description": "Stop 7467-4854-654756426850", agitating contents of 'reactor' .", "name" : "operations " : { "StartAgitation" , "actions " : [

[0627] "description": "Start agitating contents of 'reactor' at "StirringOperationType . STOP" '400.0 RPM' . ", ] , "operations " : { "parameters " : [ "actions " : [ {

[0628] "actioner" :

[0629] "StirringOperationType . START" "reactor_hotplate" ] , } "parameters " : [ ] { } "actioner " : } "reactor_hotplate" , ]

[0630] "input_value" : }, 400 {

[0631] } "id": "74687461-6561-6943- ] 6a4c-434b5a6c686f ", } "name": "Heatchill",

[0632] }, "description": "Heat

[0633] { 'reactor' contents to '22.0 °C

[0634] "id": "4164646f-664b- for '4.0 h' , whilst stirring at 6f 48-5453-7a554d744b65 " , '400 RPM' . ", "name": "Add", "operations " : { "description": "Manual "actions " : [ Add required . \nAdd '6.7 ml' , into 'reactor' from 'N-ethyl-N- "StirringOperationType . START" , isopropylpropan-2-amine ' , \nat rate '10.0 mL / min' . Use a minimal "TemperatureOperationType . START" , amount of ' N, N-dimethyl formamide ' to rinse if necessary.", "TemperatureOperationType . GET_TEMP "operations " : { ERATURE", "actions " : [

[0635] "SynchronizationOperationType . STAR

[0636] "ChemicalHandlingOperationType . MAN T", UAL"

[0637] ] , "SynchronizationOperationType . GET_ "parameters " : [ TIME", {

[0638] "actioner" : "SynchronizationOperationType . STOP "manual " ,

[0639] "input_value" : { "text" : "TemperatureOperationType . STOP" ,

[0640] "Manual Add required . \nAdd '6.7 mL ' , into 'reactor' from 'N-ethyl- "StirringOperationType . STOP" N-isopropylpropan-2-amine ' , \nat ] , rate '10.0 mL / min' . Use a minimal "parameters " : [ amount of ' N, N-dimethyl formamide ' { to rinse if necessary." "actioner" :

[0641] } "reactor_hotplate" ,

[0642] } "input_value" : 400 ] }, } {

[0643] }, "actioner" : { "reactor_chiller" ,

[0644] "id": " 7474746e- 6174- "input_value" : 22

[0645] 008773897 }, 400

[0646] { }

[0647] "actioner " : ] "reactor_chiller" , }

[0648] "target_value" : 22 }, }, { { "id": "64646464-4255-

[0649] "actioner": "timer", 6862-714d-4265446c714c", "input_value" : 240 "name": "Add", }, "description": "Add { '100.0 mL ' , into 'reactor' from

[0650] "actioner": "timer", 'ethyl acetate ' , \nat rate '70.0 "target_value" : 240 mL / min' . Use a minimal amount of }, 'ethyl acetate' to rinse if { necessary . " ,

[0651] "actioner": "timer" "operations " : { }, "actions " : [ {

[0652] "actioner" : "ChemicalHandlingOperationType .ADD

[0653] "reactor_chiller " !!

[0654] }, ] ,

[0655] { "parameters " : [

[0656] "actioner" : {

[0657] "reactor_hotplate" "actioner" :

[0658] } "backbone" ,

[0659] ] "source" : } "solvent_4",

[0660] }, "target" :

[0661] { "reactor" ,

[0662] "details " : { "input_value" : "name" : 0.1,

[0663] "AddWithConditionsControl " , "rate" : 0.07, "repeats" : 1, "description": "Add "flushing_solvent" : "solvent_4",

[0664] '100.0 mL ' , into 'reactor' from " f lushing_gas " : 'ethyl acetate ' , \nat rate '10.0 "pas sive_mani fold" mL / min' . Use a minimal amount of } 'ethyl acetate' to rinse if ] necessary . \nControl the conditions } of 'reactor' by stirring at '400 }, RPM' . " {

[0665] }, "id": " 6f 6f 696f-7461-

[0666] "steps" : [ 6967-5976-546b43636a77",

[0667] { "name" :

[0668] "id": " 6969696e— 6967 — "StopAgitation" ,

[0669] 746e- 6452-4a484e674 f 42 " , "description": "Stop "name" : agitating contents of 'reactor' .",

[0670] "StartAgitation" , "operations " : {

[0671] "description": "Start "actions " : [ agitating contents of 'reactor' at '400.0 RPM' . ", "StirringOperationType . STOP"

[0672] "operations " : { ] , "actions " : [ "parameters " : [ {

[0673] "StirringOperationType . START" "actioner" :

[0674] ] , "reactor_hotplate"

[0675] "parameters " : [ }

[0676] { ]

[0677] "actioner" : } "reactor_hotplate" , }

[0678] "input_value" : ]

[0679] 008773897 },

[0680] { "VacuumOperationType . STOP"

[0681] "details " : { ] ,

[0682] "name" : "parameters " : [

[0683] "Trans f erWithCondit ions Control " , { "repeats" : 1, "actioner" : "description": "Transfer "manual " , '130.0 ml1, from 'reactor' to "input_value" : { ' product_f lask ' , \nat rate '20.0 "text" : mL / min ' . \nControl the conditions "Please lower the filtration tube of 'reactor' by stirring at '400 to the bottom of the 'reactor' ." RPM' . " }

[0684] }, },

[0685] "steps" : [ {

[0686] { "actioner" :

[0687] "id": "69746969-6769- "pneumatic_controller " , 6e74-784c-4764726f 7751", "input_value" :

[0688] "name" : 0.01,

[0689] "StartAgitation" , "target" :

[0690] "description": "Start "product_f lask" agitating contents of 'reactor' at }, '400.0 RPM' . ", {

[0691] "operations " : { "actioner" : "actions " : [ "timer" ,

[0692] "input_value" : 5

[0693] "StirringOperationType . START" },

[0694] ] , {

[0695] "parameters " : [ "actioner" :

[0696] { "timer" ,

[0697] "actioner " : "target_value" :

[0698] "reactor_hotplate" , 5

[0699] "input_value" : }, 400 {

[0700] } "actioner" :

[0701] ] "timer"

[0702] } },

[0703] }, {

[0704] { "actioner" :

[0705] "id": "5473666e-5466- "pneumatic_cont roller " 666e-596b-427045755959", }

[0706] "name": "Transfer", ] "description" : }

[0707] "Transfer '130.0 mL ' , from }, 'reactor' to ' product_f lask ' , \nat { rate '20.0 mL / min' .", "id": "6e74616e-676e-

[0708] "operations " : { 6174-594a-4a6359784a55 " , "actions " : [ "name" :

[0709] "StopAgitation" ,

[0710] "ChemicalHandlingOperationType . MAN "description": "Stop UAL", agitating contents of 'reactor' .", "operations " : {

[0711] "VacuumOperationType . START" , "actions " : [

[0712] "SynchronizationOperationType . STAR "StirringOperationType . STOP" T", ] , "parameters " : [

[0713] "SynchronizationOperationType . GET_ { TIME", "actioner" :

[0714] "reactor_hotplate"

[0715] "SynchronizationOperationType . STOP }

[0716] ]

[0717] 008773897 } {

[0718] } "actioner" :

[0719] ] "backbone" ,

[0720] }, "cleaning_solvent" :

[0721] { "solvent_4",

[0722] "id": " 6e 676164— 6e 6c— 6e 64 — " f lushing_gas " : 4a48-78627845514d" , "passive_manifold" ,

[0723] "name": "ResetHandling" , "cleaning_repeats " : "description": "Ensure any 3, hardware used for chemical " f lushing_repeats " : handling is clean . \nClean with 1 solvent 'ethyl acetate' and use } gas 'nitrogen' to aid ] drying . \nRepeat '3' times.", } "operations " : { } "actions " : [ ]

[0724] }

[0725] "ChemicalHandlingOperationType . RES } ET"

[0726] ] , "parameters " : [

[0727] Generated XDL for Analysis - NMR

[0728] "operations " : { "actions " : [

[0729] {

[0730] "id" : "05fdc83f-0bad-38ba-96f3-

[0731] "ChemicalHandlingOperationType . TRA

[0732] 8 Idf 3b8d3908 " , NSFER"

[0733] "name": "2_W001_1099-5-MR- Cl_Executable" , ] ,

[0734] "parameters " : [

[0735] "xdl_name": "1099-5-MR-C1", "graph": "W_001_v2_Vl . j son" , {

[0736] "actioner " : "chempiler_version" : "curie-

[0737] "backbone" , chemify-2.10.9",

[0738] "source" :

[0739] "XDL_standard_version" : "3.6.0",

[0740] "crude_l " , "procedure" : {

[0741] "target" : "details " : {

[0742] "separator" ,

[0743] "input_value" :

[0744] }, 0.13,

[0745] "steps" : [

[0746] "rate" : 0.07,

[0747] { " f lushing_gas " :

[0748] "details " : {

[0749] "solvent_air" ,

[0750] "name" : "Wash" , "repeats" : 1,

[0751] "rinsing_solvent" : null, "description": "Wash contents of 'crude_l' with '10%

[0752] "rinsing_volume" : 0, sodium chloride (aq) ' , 3 times . \nTransfer washed product

[0753] "rinsing_repeats" : 0 (top phase) to 'product_l' and discard bottom phase to 'waste_l' , } following the final wash." ]

[0754] }

[0755] },

[0756] "steps" : [ },

[0757] {

[0758] { "details " : {

[0759] "id": "616e726e-5466-

[0760] "name": "Repeat", 5472-554d- 626553416757 " , "repeats" : 3,

[0761] "name": "Transfer", "description" : "description" :

[0762] "Repeat '3' times:" "Transfer '130.0 mL ' , from 'crude_l' to ' separator ' , \nat rate },

[0763] "steps" : [ '70.0 mL / min ' . " ,

[0764] 008773897 { "id" : "6e6e7361- "SynchronizationOperationType . STOP 6154-5472-7861-76496a4a4a76", "name" :

[0765] "Transfer" , "StirringOperationType . STOP" ,

[0766] "description" : "Transfer '50.0 ml1, from '10% "SynchronizationOperationType . STAR sodium chloride (aq) ' to T", ' separator ' , \nat rate '115.0 mL / min ' . " , "SynchronizationOperationType . GET_

[0767] "operations " : { TIME", "actions " : [

[0768] "SynchronizationOperationType . STOP

[0769] "ChemicalHandlingOperationType . TRA !! NSFER" ] ,

[0770] ] , "parameters " : [ "parameters " : [ {

[0771] { "actioner" :

[0772] "actioner " : "separator" , "backbone" ,

[0773] "source" : "input_value" : 600 "w_solvent_2 " , },

[0774] "target" : { "separator" , "actioner" :

[0775] "timer" ,

[0776] "input_value" : 0.05,

[0777] "rate" : "input_value" : 5

[0778] 0.115, },

[0779] {

[0780] " f lushing_gas " : "solvent_air" , "actioner" :

[0781] "timer" ,

[0782] "rinsing_solvent" : null,

[0783] "target_value" : 5

[0784] "rinsing_volume" : 0, },

[0785] {

[0786] "rinsing_repeats" : 0 "actioner" :

[0787] } "timer" ] }, } { }, "actioner" : { "separator"

[0788] "id": "6c747465- }, 746C-7465-7648-674556776146", {

[0789] "name" : "actioner" : "SeparateSettle" , "timer" ,

[0790] "description": "1. Agitate 'separator' vigorously "input_value" : 5 (for '5.0 min ' ) . \nMaking sure that }, any gas built up is released { regularly . \n2. Allow the phases to "actioner" : settle (for '5.0 min' ) .", "timer" , "operations " : { "actions " : [ "target_value" : 5

[0791] },

[0792] "StirringOperationType . START" , {

[0793] "actioner" :

[0794] "SynchronizationOperationType . STAR "timer" T", }

[0795] ]

[0796] "SynchronizationOperationType . GET_ } TIME", },

[0797] 008773897 { "id": "65656565- " f lushing_gas " : "solvent_air" ,

[0798] 6850-6865- 6d64-4d4e526b4648 " , "name" : "rinsing_solvent" : null,

[0799] "SeparatePhases " , "description" : "rinsing_volume" : 0,

[0800] "Ensure there is a biphasic mixture in the "rinsing_repeats" : 0

[0801] ' separator \nTransfer the bottom } phase to ' buf f er_f lask_l ' . " , ] "operations " : { } "actions " : [ }

[0802] ]

[0803] "SeparationOperationType . SEPARATE_ }, PHASES" {

[0804] ] , "id": "656e7254-6173- "parameters " : [ 7273-7046-587877526c78" ,

[0805] { "name": "Transfer",

[0806] "actioner " : "description" : "backbone" , "Transfer '130.0 mL ' , from

[0807] "source" : 'separator' to ' product_l ' , \nat "separator" , rate '109.0 mL / min' .",

[0808] "target" : "operations " : {

[0809] "buf f er_f lask_l " , "actions " : [

[0810] "target_value" : "low", "ChemicalHandlingOperationType . TRA

[0811] "rate" : NSFER"

[0812] 0.04, ] ,

[0813] "parameters " : [

[0814] " f lushing_gas " : "separator_air" { } "actioner" :

[0815] ] "backbone" , } "source" :

[0816] }, "separator" , { "target" :

[0817] "id": "66657265- "product_l " , 7372-7272-724d-704c664b507a", "input_value" : "name" : 0.13,

[0818] "Transfer" , "rate" : 0.109, "description" : " f lushing_gas " :

[0819] "Transfer '130.0 mL ' , from "solvent_air" ,

[0820] ' buf f er_f lask_l ' to ' waste_l ' , \nat rate '109.0 mL / min' .", "rinsing_solvent" : null, "operations " : { "actions " : [ "rinsing_volume" : 0,

[0821] "ChemicalHandlingOperationType . TRA "rinsing_repeats" : 0 NSFER" }

[0822] ] , ] "parameters " : [ }

[0823] { }

[0824] "actioner" : ] "backbone" , }

[0825] "source" : ]

[0826] "buf f er_f lask_l " , } "target" : }

[0827] "waste_l " ,

[0828] "input_value" : 0.13,

[0829] "rate" : 0.109,

[0830] 008773897 Generated XDL for Evaporation

[0831] NT",

[0832] { "EvaporationOperationType . GET_VACU "id" : "f355eeea-696c-3617-8bc7- UM_PRESSURE",

[0833] 2c310a7d7e23",

[0834] "name": "3_E001_1099-5-MR-

[0835] "EvaporationOperationType . STOP_VEN Cl_Executable" , T",

[0836] "xdl_name": "1099-5-MR-C1", "graph": "E_001_V6. j son" ,

[0837] "CondenserOperationType . STOP" , "chempiler_version": "curie- chemify-2.10.9",

[0838] "TemperatureOperationType . STOP" ,

[0839] "XDL_standard_version" : "3.6.0", "procedure" : {

[0840] "StirringOperationType . STOP" "details " : { ] , "parameters " : [ }, "steps" : [ {

[0841] "actioner " : { "rotavap" , "id": "61657461-7472-7461- "input_value" : 150 7346-59696c61436e " ,

[0842] "name": "Evaporate", }, "description": "Evaporate {

[0843] "actioner" : contents of ' rotavap ' under vacuum

[0844] "rotavap" , ( '140.0 mbar' ) for '6.67 "input_value" : 5 min' .\nSet heating bath temperature to '40.0 °C , }, condenser temperature to '5.0 °C {

[0845] "actioner" : and stirring speed to '150 RPM' .",

[0846] "rotavap" , "operations " : { "input_value" : 40 "actions " : [ },

[0847] "StirringOperationType . START" , {

[0848] "actioner" :

[0849] "rotavap" ,

[0850] "CondenserOperationType . START" , "target_value" : 5

[0851] "TemperatureOperationType . START" , }, {

[0852] "actioner" :

[0853] "CondenserOperationType . GET_TEMPER

[0854] "rotavap" , ATURE " , "target_value" : 40

[0855] "TemperatureOperationType . GET_TEMP }, ERATURE", {

[0856] "actioner" :

[0857] "rotavap" ,

[0858] "EvaporationOperationType . START" , "input_value" : 0.14

[0859] "EvaporationOperationType . GET_VACU }, UM_PRESSURE", {

[0860] "actioner" :

[0861] "rotavap" ,

[0862] "SynchronizationOperationType . STAR

[0863] "target_value" : 0.14 T", },

[0864] "SynchronizationOperationType . GET_ {

[0865] "actioner": "timer", TIME", "input_value" : 6.67

[0866] "SynchronizationOperationType . STOP }, {

[0867] "actioner": "timer", "target_value" : 6.67

[0868] "EvaporationOperationType . STOP" , },

[0869] "EvaporationOperationType . START_VE {

[0870] "actioner": "timer"

[0871] 008773897 }, "rinsing_volume" : 0, { "rinsing_repeats" : 0 "actioner " : }

[0872] "rotavap" ]

[0873] }, }

[0874] { },

[0875] "actioner" : {

[0876] "rotavap" "id": "76657461-6174-706f-

[0877] }, 4361-75754a506576 " ,

[0878] { "name": "Evaporate",

[0879] "actioner" : "description": "Evaporate

[0880] "rotavap" , contents of 'rotavap' under vacuum

[0881] "target_value" : ( '140.0 mbar' ) for '6.67 1.01325 min' .\nSet heating bath

[0882] }, temperature to '40.0 °C ,

[0883] { condenser temperature to '5.0 °C

[0884] "actioner" : and stirring speed to '150 RPM' .",

[0885] "rotavap" "operations " : {

[0886] }, "actions " : [

[0887] {

[0888] "actioner" : "StirringOperationType . START" ,

[0889] "rotavap"

[0890] }, "CondenserOperationType . START" ,

[0891] {

[0892] "actioner" : "TemperatureOperationType . START" ,

[0893] "rotavap"

[0894] }, "CondenserOperationType . GET_TEMPER

[0895] { ATURE " ,

[0896] "actioner" :

[0897] "rotavap" "TemperatureOperationType . GET_TEMP

[0898] } ERATURE",

[0899] ]

[0900] } "EvaporationOperationType . START" ,

[0901] },

[0902] { "EvaporationOperationType . GET_VACU

[0903] "id": "54725472-6673-7265- UM_PRESSURE", 6246- 61744973714a " ,

[0904] "name": "Transfer", "SynchronizationOperationType . STAR "description": "Transfer T",

[0905] '75.0 ml1, from 'rotavap' to

[0906] ' waste_l ' , \nat rate '60.0 "SynchronizationOperationType . GET_ mL / min ' . " , TIME", "operations " : { "actions " : [ "SynchronizationOperationType . STOP

[0907] "ChemicalHandlingOperationType . TRA NSFER" "EvaporationOperationType . STOP" ,

[0908] ] , "parameters " : [ "EvaporationOperationType . START_VE

[0909] { NT",

[0910] "actioner" :

[0911] "backbone" , "EvaporationOperationType . GET_VACU

[0912] "source": "rotavap", UM_PRESSURE", "target": "waste_l", "input_value" : "EvaporationOperationType . STOP_VEN

[0913] 0.075, T",

[0914] "rate" : 0.06,

[0915] " f lushing_gas " : "CondenserOperationType . STOP" ,

[0916] "air" ,

[0917] "rinsing_solvent" : "TemperatureOperationType . STOP" , null,

[0918] 008773897 StirringOperationType . STOP" 1.01325 ] , }, "parameters " : [ { { "actioner" : "actioner " : "rotavap" rotavap" , },

[0919] "input_value" : 150 { }, "actioner" : { "rotavap"

[0920] "actioner" : }, rotavap" , {

[0921] "input_value" : 5 "actioner" : }, "rotavap" { },

[0922] "actioner" : { rotavap" , "actioner" : "input_value" : 40 "rotavap" }, } { ]

[0923] "actioner" : } rotavap" , },

[0924] "target_value" : 5 { }, "id": "72666673-5465-6e72- { 7868-626866775971",

[0925] "actioner" : "name": "Transfer", rotavap" , "description": "Transfer

[0926] "target_value" : 40 '75.0 ml1, from 'rotavap' to }, ' waste_l ' , \nat rate '60.0 { mL / min ' . " ,

[0927] "actioner" : "operations " : { rotavap" , "actions " : [

[0928] "input_value" : 0.14 }, "ChemicalHandlingOperationType . TRA { NSFER"

[0929] "actioner" : ] , rotavap" , "parameters " : [

[0930] "target_value" : 0.14 { }, "actioner" : { "backbone" ,

[0931] "actioner": "timer", "source": "rotavap", "input_value" : 6.67 "target": "waste_l", }, "input_value" : { 0.075,

[0932] "actioner": "timer", "rate" : 0.06, "target_value" : 6.67 " f lushing_gas " : }, "air" , { "rinsing_solvent" :

[0933] "actioner": "timer" null, }, "rinsing_volume" : 0, { "rinsing_repeats" : 0

[0934] "actioner" : } rotavap" ]

[0935] }, } { }, "actioner" : { rotavap" "id": "746f656f-7070-7061-

[0936] }, 4d4e-714375476141 " , { "name": "Evaporate",

[0937] "actioner" : "description": "Evaporate rotavap" , contents of 'rotavap' under vacuum

[0938] "target_value" : ( '20.0 mbar' ) for '20.0 min' .\nSet

[0939] 008773897 heating bath temperature to '40.0 { °C , condenser temperature to '5.0 "actioner" : °C and stirring speed to '150 "rotavap" , RPM' . ", "input_value" : 40

[0940] "operations " : { }, "actions " : [ {

[0941] "actioner" :

[0942] "StirringOperationType . START" , "rotavap" , "target_value" : 5

[0943] "CondenserOperationType . START" , }, {

[0944] "TemperatureOperationType . START" , "actioner" :

[0945] "rotavap" ,

[0946] "CondenserOperationType . GET_TEMPER "target_value" : 40 ATURE " , }, {

[0947] "TemperatureOperationType . GET_TEMP "actioner" : ERATURE", "rotavap" , "input_value" : 0.02

[0948] "EvaporationOperationType . START" , }, {

[0949] "EvaporationOperationType . GET_VACU "actioner" : UM_PRESSURE", "rotavap" ,

[0950] "target_value" : 0.02

[0951] "SynchronizationOperationType . STAR }, T", {

[0952] "actioner": "timer",

[0953] "SynchronizationOperationType . GET_ "input_value" : 20 TIME", },

[0954] {

[0955] "SynchronizationOperationType . STOP "actioner": "timer", "target_value" : 20 },

[0956] "EvaporationOperationType . STOP" , {

[0957] "actioner": "timer"

[0958] "EvaporationOperationType . START_VE }, NT", {

[0959] "actioner" :

[0960] "EvaporationOperationType . GET_VACU "rotavap" UM_PRESSURE", },

[0961] {

[0962] "EvaporationOperationType . STOP_VEN "actioner" : T", "rotavap"

[0963] },

[0964] "CondenserOperationType . STOP" , {

[0965] "actioner" :

[0966] "TemperatureOperationType . STOP" , "rotavap" ,

[0967] "target_value" :

[0968] "StirringOperationType . STOP" 1.01325 ] , }, "parameters " : [ { { "actioner" :

[0969] "actioner " : "rotavap"

[0970] "rotavap" , }, "input_value" : 150 { }, "actioner" : { "rotavap"

[0971] "actioner" : },

[0972] "rotavap" , { "input_value" : 5 "actioner" : }, "rotavap"

[0973] 008773897 }, "backbone" ,

[0974] { "source": "rotavap",

[0975] "actioner " : "target": "waste_l",

[0976] "rotavap" "input_value" : 0.05,

[0977] } "rate" : 0.06,

[0978] ] " f lushing_gas " :

[0979] } "air" ,

[0980] }, "rinsing_solvent" :

[0981] { null,

[0982] "id": "72726166-5461-6673- "rinsing_volume" : 0,

[0983] 4644- 69634d707266 " , "rinsing_repeats" : 0

[0984] "name": "Transfer", "description": "Transfer

[0985] '50.0 ml1, from 'rotavap' to

[0986] ' waste_l ' , \nat rate '60.0 mL / min ' . " ,

[0987] "operations " : { "actions " : [

[0988] "ChemicalHandlingOperationType . TRA NSFER"

[0989] ] ,

[0990] "parameters " : [

[0991] { "actioner" :

[0992] Generated XDL for Analysis - NMR

[0993] Ascend Aeon 700", "target": "Bruker

[0994] { Ascend Aeon 700",

[0995] "id" : "efelldel-2bbe-38f7-90dd- "input_value" : { 10610a0baafa" , "methods": [

[0996] "name": "4_A001_NMR_1099-5-MR- Cl_Executable" , {

[0997] "xdl_name": "1099-5-MR-C1", "method_requirements " : {

[0998] "graph": "A_001_V2. j son" , "chempiler_version" : "curie- "NMR_experiment" : "1H", chemify-2.10.9",

[0999] "XDL_standard_version" : "3.6.0", "no_of_scans " : null,

[1000] "procedure" : {

[1001] "details " : { "NMR_temperature" : "22 °C" },

[1002] }, "method_file" :

[1003] "steps" : [ null

[1004] {

[1005] "id": "6e6e7552-4e4d-7757- },

[1006] 5467- 626f 567a785a " , {

[1007] "name": "RunNMR",

[1008] "method_requirements " : { "description": "Manual

[1009] RunNMR required . \nPerform NMR "NMR_experiment" : "13C", analysis ( '1H' ) of ' sample_f lask ' in solvent 'CDC13' .", "no_of_scans " : null,

[1010] "operations " : { "actions " : [ "NMR_temperature" : "22 °C"

[1011] "NMROperationType . MANUAL" }, "method_file" :

[1012] ] , null

[1013] "parameters " : [ }

[1014] {

[1015] "actioner" : ] , "text": "Sample

[1016] "manual " , name(s) should be: 284d0fe4-f f 88- "source": "Bruker

[1017] 008773897 3461- 98ac-bf 835003892d_l 099-5-MR- Transfer required. \nTransfer '0.0 Cl_sample_f lask, 284d0fe4-f f 88- mL ' , from ' sample_f lask ' to 3461- 98ac-bf 835003892d_l 099-5-MR- 'Bruker Ascend Aeon 700' ,\nat rate Cl_sample_f lask" , '60.0 mL / min ' . "

[1018] "sample_info" : { } }

[1019] "source_XDL_name" : "284d0fe4-f f 88- ] 3461- 98ac-bf 835003892d_l 099-5-MR- }

[1020] Cl", },

[1021] "sample_names" : {

[1022] [ "id": "61767476-6544-6574-

[1023] "284d0fe4- 5962-77566b556c64 " , f 188-3461-98ac-bf 835003892d_l 099- "name": "RetrieveData" , 5-MR-Cl_sample_f lask" , "description": "Retrieve

[1024] "284d0fe4- data for ' NMR ' analysis of ff88-3461-98ac-bf835003892d_1099- ' sample_f lask ' . " , 5-MR-Cl_sample_f lask" "operations " : {

[1025] ] , "actions " : [

[1026] "sample_concentrations" : [ "NMROperationType . RETRIEVE_DATA" "0.05 mM" , ] , "0.05 mM" "parameters " : [

[1027] ] , {

[1028] "actioner": "Bruker

[1029] "sample_solvents" : [ Ascend Aeon 700", "CDC13", "source": "Bruker "CDC13" Ascend Aeon 700",

[1030] ] "target": "Bruker

[1031] } Ascend Aeon 700",

[1032] } "input_value" : {

[1033] } "sample_step_id" :

[1034] ] " 6e6e7552-4e4d-7757-5467-

[1035] } 626f 567a785a " ,

[1036] }, "sample_names" : [

[1037] { "284d0 f e4- f f 88-

[1038] "id": "66617366-5465-736e- 3461- 98ac-bf 835003892d_l 099-5-MR- 6766-764d70756974 " , Cl_sample_f lask" ,

[1039] "name": "Transfer", "284d0fe4-ff88- "description": "Manual 3461-98ac-bf835003892d_1099-5-MR-

[1040] Transfer required. \nTransfer '0.0 Cl_sample_f lask" ml1, from ' sample_f lask ' to ]

[1041] 'Bruker Ascend Aeon 700' ,\nat rate } '60.0 mL / min ' . " , }

[1042] "operations " : { ] "actions " : [ }

[1043] }

[1044] "ChemicalHandlingOperationType . MAN ] UAL" }

[1045] ] , }

[1046] "parameters " : [

[1047] { "actioner " :

[1048] "manual " , "input_value" : { "text": "Manual

[1049] Generated XDL for Analysis - UPLC

[1050] "name" : "5_A001_LCMS_1099-5-MR-

[1051] Cl_Executable" ,

[1052] { "xdl_name": "1099-5-MR-C1",

[1053] "id" : "bdf2ecl2-c3c3-38a5-9659- "graph": "A_001_V2. j son" ,

[1054] 3eflafcc345d", "chempiler_version" : "curie-

[1055] 008773897 chemi fy-2.10.9", "XDL_standard_version" : "3.6.0", "LC_method_mobile_phase_additive_t "procedure" : { ype" : "basic" , "details " : {

[1056] "LC_method_mobile_phase_additive" : }, null, "steps" : [ { "LC_method_mobile_phase_additive_p

[1057] "id": "6e4d5253-5275-4d52- ercentage": null, 6469- 6d6d49526277 " ,

[1058] "name": "RunLCMS", "UV_wavelengths " : null, "description": "Manual RunLCMS required . \nPerform LCMS "min_UV_wavelength" : null, analysis ( 'ESI' , 'positive' mode) of ' sample_f lask ' using a 'C18' "max_UV_wavelength" : null, column. \n The required solvent system is 'analytical hexane' "MS_polarity" : "positive", (weak component) in 'analytical acetonitrile' (strong component) , "MS_ionisation_method" : "ESI " , with additive of (basic additive ) . " , "additional_detectors " : null, "operations " : { "min_mz " : "actions " : [ null,

[1059] "maxjnz " :

[1060] "LCMSOperationType . MANUAL" null, ] , "parameters " : [ "LC_method_time" : "20.0 min", {

[1061] "actioner " : "LC_method_mobile_phase_weak_compo

[1062] "manual " , nent_start_percentage" : null, "source": "Waters

[1063] Acquity Premier Acquity SQDetector "LC_method_mobile_phase_weak_compo 2", nent_end_percentage" : null "target": "Waters }, Acquity Premier Acquity SQDetector "method_file" : 2", null "input_value" : { } "methods": [ ] , { "text": "Sample name(s) should be: 284d0fe4-f f 88- "method_requirements " : { 3461- 98ac-bf 835003892d_l 099-5-MR- Cl_sample_f lask" , "LC_column_type" : "hplc_column" , "sample_info" : { "LC_column_length" : null, "source_XDL_name" : "284d0fe4-f f 88- 3461- 98ac-bf 835003892d_l 099-5-MR-

[1064] "LC_column_diameter " : null, Cl",

[1065] "sample_names" :

[1066] "LC_column_particle_size" : null, [

[1067] "284d0fe4-

[1068] "LC_column_stationary_phase" : ff88-3461-98ac-bf835003892d_1099- "C18", 5-MR-Cl_sample_f lask"

[1069] ] ,

[1070] "LC_method_mobile_phase_strong_com ponent": "analytical "sample_concentrations" : [ acetonitrile" , "0.05 mM" ] ,

[1071] "MS_ion_mass " : null,

[1072] "sample_solvents" : [

[1073] "LC_method_mobile_phase_weak_compo "analytical nent": "analytical hexane", acetonitrile"

[1074] 008773897 ] "name": "RetrieveData" , } "description": "Retrieve } data for ' LCMS ' analysis of

[1075] } ' sample_f lask ' . " , ] "operations " : { } "actions " : [

[1076] },

[1077] { "LCMSOperationType . RETRIEVE_DATA"

[1078] "id": " 66727265-736e-7272- ] , 4141- 6255616f 6e54 " , "parameters " : [

[1079] "name": "Transfer", { "description": "Manual "actioner": "Waters

[1080] Transfer required. \nTransfer '0.0 Acquity Premier Acquity SQDetector ml1, from ' sample_f lask ' to 2", 'Waters Acquity Premier Acquity "source": "Waters SQDetector 2 ' , \nat rate '60.0 Acquity Premier Acquity SQDetector mL / min ' . " , 2", "operations " : { "target": "Waters "actions " : [ Acquity Premier Acquity SQDetector 2",

[1081] "ChemicalHandlingOperationType . MAN "input_value" : { UAL" "sample_step_id" :

[1082] ] , " 6e4d5253-5275-4d52- 6469- "parameters " : [ 6d6d49526277 " ,

[1083] { "sample_names" : [ "actioner " : "284d0fe4-ff88-

[1084] "manual " , 3461-98ac-bf835003892d_1099-5-MR-

[1085] "input_value" : { Cl_sample_f lask" "text": "Manual ]

[1086] Transfer required. \nTransfer '0.0 } mL ' , from ' sample_f lask ' to } 'Waters Acquity Premier Acquity ] SQDetector 2 ' , \nat rate '60.0 } mL / min ' . " }

[1087] } ]

[1088] } }

[1089] ] } }

[1090] },

[1091] { "id": "76447474-6565-6565-

[1092] 4 f 4 f- 625144416b79 " ,

[1093] Generated XDL for Purification

[1094] { "id": "504c7272-4350-5048- 696f-724842577948",

[1095] "id" : "b51d53a3-245f-3986-8867-

[1096] "name": "RunPrepHPLC" , 551dal09cdc2 " , "description": "Manual

[1097] "name" : "6_P001_PrepHPLC_1099-5- RunPrepHPLC required . \nPuri fy the MR-Cl_Executable" , contents of ' sample_f lask ' via

[1098] "xdl_name": "1099-5-MR-C1", PrepHPLC using a 'C18' column. \n

[1099] "graph": "P_001_V3. j son" , The required solvent system is

[1100] "chempiler_version" : "curie- 'analytical hexane' (weak chemify-2.10.9", component) in 'analytical

[1101] "XDL_standard_version" : "3.6.0", acetonitrile' (strong component) ,

[1102] "procedure" : { with additive of (basic

[1103] "details " : { additive ) . " , "operations " : {

[1104] }, "actions " : [

[1105] "steps" : [

[1106] 008773897 "PrepHPLCOperationType . MANUAL" "LC_method_time" : "1.0 h", ] , "parameters " : [ "LC_method_mobile_phase_additive_t { ype" : "basic" , "actioner " : "manual " , "LC_method_mobile_phase_additive" : "source": "Teledyne null, ACCQPrep HP 150 Purlon S", "target": "Teledyne "LC_method_mobile_phase_additive_p ACCQPrep HP 150 Purlon S", ercentage": null "input_value" : { }, "methods": [ "method_file" : { null

[1107] } "method_requirements " : { ] ,

[1108] "text": "Sample "sample_loading" : "500.0 mg", name(s) should be: d9236af 4-6442- 3830-b4e4-9el77ba03763_1099-5-MR- "LC_method_mobile_phase_strong_com Cl_sample_f lask" , ponent": "analytical "sample_info" : { acetonitrile" ,

[1109] "source_XDL_name" : "d9236af 4-6442- "LC_method_mobile_phase_weak_compo 3830-b4e4-9el77ba03763_1099-5-MR- nent": "analytical hexane", Cl",

[1110] "sample_names" : "LC_method_mobile_phase_weak_compo [ nent_start_percentage" : null, "d9236af4- 6442-3830-b4e4-9el77ba03763_1099- "LC_method_mobile_phase_weak_compo 5-MR-Cl_sample_f lask" nent_end_percentage" : null, ] , "LC_column_type" : "sample_concentrations" : [ "prep_hplc_column" , "0.05 mM"

[1111] ] , "LC_column_length" : null,

[1112] "sample_solvents" : [ "LC_column_diameter " : null, "analytical acetonitrile" "LC_column_particle_size" : null, ]

[1113] } "LC_column_stationary_phase" : } "C18", }

[1114] ] "UV_wavelengths " : null, }

[1115] }, "min_UV_wavelength" : null, {

[1116] "id": "6e656e73-5465-726e- "max_UV_wavelength" : null, 6f 54-7a6b4b447076" ,

[1117] "name": "Transfer", "MS_polarity" : null, "description": "Manual

[1118] Transfer required. \nTransfer '0.0 "MS_ionisation_method" : null, mL ' , from ' sample_f lask ' to 'Teledyne ACCQPrep HP 150 Purlon

[1119] "MS_ion_mass " : null, S ' , \nat rate '60.0 mL / min' .",

[1120] "min_mz " : "operations " : { null, "actions " : [

[1121] "max_mz " : null, "ChemicalHandlingOperationType . MAN UAL"

[1122] "additional_detectors " : null, ] ,

[1123] 008773897 "parameters " : [ { { "actioner" : "actioner " : "Teledyne ACCQPrep HP 150 Purlon "manual " , S", "input_value" : { "source": "Teledyne "text": "Manual ACCQPrep HP 150 Purlon S", Transfer required. \nTransfer '0.0 "target": "Teledyne ml1, from ' sample_f lask ' to ACCQPrep HP 150 Purlon S", 'Teledyne ACCQPrep HP 150 Purlon "input_value" : { S ' , \nat rate '60.0 mL / min' ." "sample_step_id" : } " 504c7272-4350-5048-696f- } 724842577948", ] "sample_names" : [

[1124] } "d9236af4-6442-

[1125] }, 3830-b4e4-9el77ba03763_1099-5-MR-

[1126] { Cl_sample_f lask"

[1127] "id": "61616174-6561-7661- ] 6178-504846647a58 " , }

[1128] "name": "RetrieveData" , } "description": "Retrieve ] data for 'PrepHPLC' analysis of } ' sample_f lask ' . " , } "operations " : { ] "actions " : [ }

[1129] }

[1130] "PrepHPLCOperationType . RETRIEVE_DA TA"

[1131] ] , "parameters " : [ Generated XDL for Analysis - NMR

[1132] {

[1133] "actioner" :

[1134] { "manual " , "id" : "51aba6ba-7ede-31ef-a31e-

[1135] "source": "Bruker fcca82e5f 63a" ,

[1136] Ascend Aeon 700",

[1137] "name": "7_A001_NMR_1099-5-MR-

[1138] "target": "Bruker Cl_Executable" ,

[1139] Ascend Aeon 700",

[1140] "xdl_name": "1099-5-MR-C1",

[1141] "input_value" : { "graph": "A_001_V2. j son" ,

[1142] "methods": [ "chempiler_version" : "curie- chemify-2.10.9", {

[1143] "XDL_standard_version" : "3.6.0",

[1144] "method_requirements " : { "procedure" : {

[1145] "details " : {

[1146] "NMR_experiment" : "1H",

[1147] }, "no_of_scans " : null,

[1148] "steps" : [

[1149] { "NMR_temperature" : "22 °C" "id": " 6e524e52-5275-4e66-

[1150] 5169-4a4464617478 " , },

[1151] "method_file" : "name": "RunNMR", null "description": "Manual

[1152] RunNMR required . \nPerform NMR }, analysis ( '1H' ) of ' sample_f lask ' { in solvent 'CDC13' .",

[1153] "method_requirements " : { "operations " : { "actions " : [

[1154] "NMR_experiment" : "13C",

[1155] "NMROperationType . MANUAL"

[1156] "no_of_scans " : null, ] , "parameters " : [

[1157] "NMR_temperature" : "22 °C"

[1158] 008773897 }, "text": "Manual

[1159] "method_file" : Transfer required. \nTransfer '0.0 null mL ' , from ' sample_f lask ' to

[1160] } 'Bruker Ascend Aeon 700' ,\nat rate

[1161] ] , '60.0 mL / min ' . "

[1162] "text": "Sample } name(s) should be: 284d0fe4-f f 88- } 3461- 98ac-bf 835003892d_l 099-5-MR- ] Cl_sample_f lask, 284d0fe4-f f 88- } 3461- 98ac-bf 835003892d_l 099-5-MR- }, Cl_sample_f lask" , {

[1163] "sample_info" : { "id": "61747669-7665-6569- 674c- 626a5870766b " ,

[1164] "source_XDL_name" : "284d0fe4-f f 88- "name": "RetrieveData" , 3461- 98ac-bf 835003892d_l 099-5-MR- "description": "Retrieve Cl", data for ' NMR ' analysis of

[1165] "sample_names" : ' sample_f lask ' . " ,

[1166] [ "operations " : {

[1167] "284d0fe4- "actions " : [ f 188-3461-98ac-bf 835003892d_l 099- 5-MR-Cl_sample_f lask" , "NMROperationType . RETRIEVE_DATA"

[1168] "284d0fe4- ] , ff88-3461-98ac-bf835003892d_1099- "parameters " : [ 5-MR-Cl_sam le_f lask" {

[1169] ] , "actioner": "Bruker Ascend Aeon 700",

[1170] "sample_concentrations" : [ "source": "Bruker

[1171] "0.05 mM" , Ascend Aeon 700", "0.05 mM" "target": "Bruker

[1172] ] , Ascend Aeon 700",

[1173] "input_value" : {

[1174] "sample_solvents" : [ "sample_step_id" :

[1175] "CDC13", "6e524e52-5275-4e66-5169- "CDC13" 4a4464617478 " , ] "sample_names" : [

[1176] } "284d0 f e4- f f 88-

[1177] } 3461- 98ac-bf 835003892d_l 099-5-MR-

[1178] } Cl_sample_f lask" ,

[1179] ] "284d0fe4-ff88-

[1180] } 3461-98ac-bf835003892d_1099-5-MR-

[1181] }, Cl_sample_f lask"

[1182] { ]

[1183] "id": " 72737272- 6661- 656e- } 546f-4c6e5571484f ", }

[1184] "name": "Transfer", ] "description": "Manual } Transfer required. \nTransfer '0.0 } mL ' , from ' sample_f lask ' to ] 'Bruker Ascend Aeon 700' ,\nat rate } '60.0 mL / min ' . " , } "operations " : { "actions " : [ "ChemicalHandlingOperationType . MAN UAL"

[1185] ] ,

[1186] "parameters " : [

[1187] {

[1188] "actioner " :

[1189] "manual " ,

[1190] "input_value" : {

[1191] 008773897 Generated XDL for Analysis - HPLC

[1192] "LC_method_mobile_phase_strong_com

[1193] { ponent": "analytical "id" : "97f8fde0-b871-3592-aea4- acetonitrile" , dde2518cf2b3",

[1194] "name" : "8_A001_LCMS_1099-5-MR-

[1195] "MS_ion_mass " : null, Cl_Executable" ,

[1196] "xdl_name": "1099-5-MR-C1",

[1197] "LC_method_mobile_phase_weak_compo "graph": "A_001_V2. j son" , nent": "analytical hexane", "chempiler_version": "curie- chemify-2.10.9",

[1198] "LC_method_mobile_phase_additive_t

[1199] "XDL_standard_version" : "3.6.0", ype" : "basic" , "procedure" : { "details " : {

[1200] "LC_method_mobile_phase_additive" : null,

[1201] },

[1202] "steps" : [

[1203] "LC_method_mobile_phase_additive_p

[1204] { ercentage": null, "id": "6e4c4352-436e-5247- 4375-4363474 f 654c " ,

[1205] "UV_wavelengths " : null, "name": "RunLCMS", "description": "Manual

[1206] "min_UV_wavelength" : null, RunLCMS required . \nPerform LCMS analysis ( 'ESI' , 'positive' mode)

[1207] "max_UV_wavelength" : null, of ' sample_f lask ' using a 'C18' column. \n The required solvent

[1208] "MS_polarity" : "positive", system is 'analytical hexane' (weak component) in 'analytical

[1209] "MS_ionisation_method" : "ESI " , acetonitrile' (strong component) , with additive of (basic

[1210] "additional_detectors " : null, additive ) . " , "min_mz " : "operations " : { null, "actions " : [

[1211] "maxjnz " : null,

[1212] "LCMSOperationType . MANUAL" ] ,

[1213] "LC_method_time" : "20.0 min", "parameters " : [ { "LC_method_mobile_phase_weak_compo

[1214] "actioner " : nent_start_percentage" : null,

[1215] "manual " , "source": "Waters

[1216] "LC_method_mobile_phase_weak_compo

[1217] Acquity Premier Acquity SQDetector nent_end_percentage" : null 2", "target": "Waters },

[1218] "method_file" : Acquity Premier Acquity SQDetector null 2", "input_value" : { } "methods": [ ] , "text": "Sample { name(s) should be: 284d0fe4-f f 88- 3461- 98ac-bf 835003892d_l 099-5-MR- "method_requirements " : { Cl_sample_f lask" ,

[1219] "sample_info" : { "LC_column_type" : "hplc_column" ,

[1220] "source_XDL_name" : "284d0fe4-f f 88- "LC_column_length" : null, 3461- 98ac-bf 835003892d_l 099-5-MR-

[1221] Cl",

[1222] "LC_column_diameter " : null,

[1223] "sample_names" :

[1224] "LC_column_particle_size" : null, [

[1225] "284d0fe4- ff88-3461-98ac-bf835003892d_1099-

[1226] "LC_column_stationary_phase" : 5-MR-Cl_sample_f lask" "C18",

[1227] 008773897 ] , { "actioner": "Waters

[1228] "sample_concentrations" : [ Acquity Premier Acquity SQDetector "0.05 mM" 2", ] , "source": "Waters

[1229] Acquity Premier Acquity SQDetector

[1230] "sample_solvents" : [ 2", "analytical "target": "Waters acetonitrile" Acquity Premier Acquity SQDetector

[1231] ] 2",

[1232] } "input_value" : {

[1233] } "sample_step_id" :

[1234] } "6e4c4352-436e-5247-4375- ] 4363474 f 654c " , } "sample_names" : [

[1235] }, "284d0fe4-ff88-

[1236] { 3461-98ac-bf835003892d_1099-5-MR-

[1237] "id": "66665472-736e-6e72- Cl_sample_f lask" 7146-4d5046507162 " , ]

[1238] "name": "Transfer", } "description": "Manual }

[1239] Transfer required. \nTransfer '0.0 ] mL ' , from ' sample_f lask ' to } 'Waters Acquity Premier Acquity } SQDetector 2 ' , \nat rate '60.0 ] mL / min ' . " , } "operations " : { } "actions " : [

[1240] "ChemicalHandlingOperationType . MAN UAL"

[1241] ] , "parameters " : [

[1242] { "actioner " :

[1243] "manual " ,

[1244] "input_value" : { "text": "Manual

[1245] Transfer required. \nTransfer '0.0 mL ' , from ' sample_f lask ' to 'Waters Acquity Premier Acquity SQDetector 2 ' , \nat rate '60.0 mL / min ' . "

[1246] }

[1247] }

[1248] ] }

[1249] },

[1250] {

[1251] "id": "65657444-7444-6961- 644a-797044455245 " ,

[1252] "name": "RetrieveData" , "description": "Retrieve data for ' LCMS ' analysis of ' sample_f lask ' . " , "operations " : { "actions " : [

[1253] "LCMSOperationType . RETRIEVE_DATA" ] , "parameters " : [

[1254] 008773897 References

[1255] A number of publications are cited above in order to more fully describe and disclose the invention and the state of the art to which the invention pertains. Full citations for these references are provided below. The entirety of each of these references is incorporated herein.

[1256] WO 2024 / 003151

[1257] WO 2019 / 170772

[1258] WO 2024 / 061972

[1259] STEINER, S. et al., 2019, “Organic synthesis in a modular robotic system driven by a chemical programming language”, Science, Vol. 363, pp 1-8.

[1260] US 5684711

[1261] 008773897

Claims

1. Claims:

1. A method of performing a synthetic procedure on a chemical processing platform, wherein the synthetic procedure comprises a plurality of different synthetic operations, the chemical processing platform comprising a network of two or more stations, wherein each station comprises one or more substations, an operation data collection unit and a control unit; and the method comprising:(a) generating an instruction set for a first synthetic operation based on a synthetic procedure using the control unit;(b) executing the first synthetic operation on a first reaction mixture to obtain a second reaction mixture using a first substation;(c) collecting first operation data about the first synthetic operation performed on the first reaction mixture using the operation data collection unit;(d) generating an instruction set for a second synthetic operation based on the synthetic procedure and the first operation data using the control unit; and(e) executing the second synthetic operation on the second reaction mixture to obtain a third reaction mixture using a second substation.

2. The method of claim 1 , wherein the step of generating an instruction set for a second synthetic operation is based on the synthetic procedure and the operation data available for each synthetic operation in the synthetic procedure.

3. The method of claims 1 or 2, wherein step (e) is preceded by a step of transferring the second reaction mixture from the first substation to the second substation of the chemical processing platform.

4. The method of claim 3, wherein the step of transferring the second reaction mixture is performed autonomously.

5. The method of any one of claims 1 to 4, wherein the chemical processing platform is an autonomous chemical processing platform, such that each of step (a) to step (e) is performed autonomously.

6. The method of claim 3, wherein the step of transferring the second reaction mixture is performed manually.

7. The method of any one of claims 1 to 6, wherein the chemical processing platform further comprises a user interface, and the user interface displays information about the instruction set used for the synthetic operation being performed.0087738978. The method of any one of claims 1 to 7, wherein step (b) is preceded by a step of compiling the instruction set into an executable format.

9. The method of any one of claims 1 to 8, wherein step (c) and step (d) occur concurrently.

10. The method of any one of claims 1 to 9, wherein step (a) is preceded by a step of providing a synthetic procedure from a human user, preferably wherein the synthetic procedure is provided in natural language.

11. The method of any one of claims 1 to 10, wherein the method comprises executing two or more synthetic operations, optionally three or more synthetic operations, on an initial reaction mixture, collecting operation data about each synthetic operation, and aggregating the operation data to generate a library of operation data.

12. The method of claim 11, wherein the method comprises generating an instruction set for the synthetic operation on the reaction mixture based on the synthetic procedure and the library of operation data.

13. The method of claim 12, wherein the method comprises generating an instruction set for a different synthetic operation on a reaction mixture based on the synthetic procedure and the library of operation data.

14. The method of any one of claims 1 to 13, further comprising:(f) comparing the operation data from a synthetic operation to reference operation data, and validating the synthetic operation based on the comparison to the reference operation data.

15. The method of claim 14, wherein the reference operation data is a library of operation data generated by aggregating operation data on two or more synthetic operations.

16. The method of any one of claims 1 to 15, wherein the instruction set is in a mark-up language, such as XDL.

17. A chemical processing platform for performing a synthetic procedure, wherein the synthetic procedure comprises a plurality of synthetic operations, the chemical processing platform comprising: a network of two or more stations, optionally three or more stations, wherein each station is in direct and / or indirect material intercommunication with each of the other stations, and each station comprises one or more substations, wherein each substation in a first station is for executing a different synthetic operation to each substation in a second station; and008773897an operation data collection unit for collecting operation data on the synthetic operation performed within the substations; and a control unit in signalling communication with the two or more stations and the operation data collection unit, wherein the control unit is for receiving operation data from the operation data collection unit, generating an instruction set based on the synthetic procedure and the operation data, and providing the substation with the instruction set for execution of the synthetic operation.

18. The chemical processing platform according to claim 17, wherein the two or more stations comprises a purification station comprising one or more purification substations for executing a purification of a reaction mixture.

19. The chemical processing platform according to claim 17 or 18, wherein the two or more stations comprises a synthesis station comprising one or more synthesis substations for executing a synthesis of a reaction mixture.

20. The chemical processing platform according to claim 19, wherein the synthesis station comprises a reaction vessel, and optionally a fluid transfer system for the addition of materials to and / or removal of materials from the reaction vessel.

21. The chemical processing platform according to any one of claims 17 to 20, further comprising a sensor for monitoring a work-up process; optionally wherein the sensor comprises a conductivity sensor and an image-based sensor; optionally wherein the imagebased sensor comprises a camera for recording still or video images.

22. The chemical processing platform according to any one of claims 17 to 21, wherein the two or more stations comprises an analysis station comprising one or more analysis substations for executing an analysis of a reaction mixture.

23. The chemical processing platform according to claim 22, wherein the analysis substation is a spectrometer selected from the group consisting of a mass spectrometer, an IR spectrometer, a hyperspectral imaging spectrometer, a Raman spectrometer, an X-ray spectrometer, and an NMR spectrometer.

24. A system comprising a plurality of chemical processing platforms according to any one of claims 17 to 23 in signalling communication, wherein at least two chemical processing platforms in the system are remotely located from each other.

25. Use of a chemical processing platform according to any one of claims 17 to 23, for performing a synthetic procedure comprising a plurality of different synthetic operations.008773897

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