JP2000218155A - Automatic synthesis device - Google Patents

Abstract

(57) [Problem] To shorten the execution time of a synthesis protocol including a production reaction performed under temperature control. SOLUTION: At the same time when dispensing by a liquid dispensing unit 3 is started, a temperature adjusting unit 27 starts an operation of raising the temperature of the reaction block 1 to a preliminary temperature raising temperature, and the temperature of the reaction block 1 is preliminarily raised. When the temperature reaches the temperature, the temperature of the reaction block 1 is maintained at the pre-heating temperature until the dispensing step is completed. When the dispensing step is completed, the temperature adjusting unit 27 raises and maintains the temperature of the reaction block 1 to the target temperature held in the target temperature holding unit 26, and the temperature of the reaction block 1 is raised to the target temperature. When the production reaction step is completed and the production reaction step is completed, the temperature control unit 27 stops sending the drive signal to the electric heater HT, and the cooling control unit 28 sends the forced cooling of the reaction block 1 to the forced cooling unit CU. The driving signal is sent to perform the cooling, and the reaction block 1 is cooled while being cooled.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an automatic synthesizer for automatically synthesizing a compound, and more particularly to a technique for shortening the time required for raising and lowering the temperature of a reaction block.

[0002]

2. Description of the Related Art Conventional automatic synthesizers used in research fields such as pharmaceuticals, life sciences, chemistry, and materials are:
As shown in FIG. 8, a reaction block 51 having a large number of reaction vessels 52 for performing a production reaction is provided, and a reagent or a solvent is dispensed into the reaction vessel 52 by a syringe 53 according to a preset dispensing procedure. At the same time, the production reaction proceeds simultaneously and parallel in each reaction vessel 52 to which the reagent and the solvent have been supplied. Therefore, in an automatic synthesizer, a plurality of compounds are synthesized simultaneously on a trial basis. Then, the compound synthesized in each reaction vessel 52 is collected for each reaction vessel 52.

In this conventional automatic synthesizing apparatus, there is provided a temperature adjusting mechanism 54 for adjusting the temperature in the reaction block 51 to a target temperature based on the actually measured temperature in the reaction block 51 and the target temperature. Is provided. That is, in the conventional apparatus, the temperature of the reaction block 51 is actually measured by a temperature sensor (not shown), the measured temperature is compared with a preset target temperature, and based on the temperature comparison result, the reaction block 51 is measured. An electric heater (not shown) is driven so that the temperature becomes the target temperature. If the target temperature is set to a temperature that is considered suitable for the production reaction, the production reaction is performed at the target temperature by the temperature control by the temperature adjustment mechanism 54, and the production reaction can be promoted.

In the conventional apparatus, a dispensing step of dispensing a reagent or a solvent into each reaction vessel 52 is performed at a predetermined temperature (eg, 25 ° C.) near room temperature, and the dispensing step is completed. After that, the electric heater is driven to start the operation of raising the temperature of the reaction block 51 from a predetermined temperature near normal temperature to a target temperature higher than that temperature, and when the temperature of the reaction block 51 reaches the target temperature. , Reaction block 5
The first reaction is performed at a target temperature while the production reaction is performed for a predetermined time. When the generation reaction is completed, the driving of the electric heater is stopped, the temperature of the reaction block 51 is decreased from the target temperature to a predetermined temperature near normal temperature, and the temperature of the reaction block 51 returns to a predetermined temperature near normal temperature. A draining step of discharging the reagent and the solvent dispensed into each reaction container 52 is performed.

[0005]

However, in this type of automatic synthesis apparatus, the reaction block 51 is provided with tens to hundreds of reaction vessels 52 such as 96 or 384, and the temperature of the reaction block 51 is controlled. The reaction block 5 is used in order to improve the heat uniformity and temperature stability of
1 has a large size and weight, and accordingly, the heat capacity of the reaction block 51 is large. Therefore, the time required to raise and lower the temperature of the reaction block 51 becomes longer.

As a result, in the conventional apparatus, it takes a long time from the completion of the dispensing process until the temperature of the reaction block 51 reaches the target temperature, and after the dispensing process starts, the drainage process ends. There is a problem that the time required to perform the operation becomes long.

Further, in the conventional apparatus, when the temperature of the reaction block 51 is lowered, only the driving of the electric heater is stopped.
Since the reaction block 51 was allowed to cool naturally, it took a long time to lower the temperature of the reaction block 51 from the target temperature to a predetermined temperature near normal temperature, and the liquid was discharged after the dispensing process was started. There is also a problem that the time required for completing the process becomes longer.

In a single synthesis protocol performed using this kind of automatic synthesizer, usually, dispensing of a first reagent or a solvent,
Formation reaction (first reaction), drainage of first reagent and solvent, second reaction
Dispensing process, generating reaction process, draining process while changing the type of reagent or solvent, such as dispensing of reagents and solvents, generating reaction (second reaction), draining of second reagent and solvent, etc. Is repeated once or more to obtain and recover the final compound. As described above, if the time required from the start of the dispensing process to the end of the drainage process in one stage of performing the production reaction under temperature control becomes longer, the total time required to execute one synthesis protocol becomes extremely long. It becomes longer and the automatic analyzer cannot be used effectively.

This kind of automatic synthesizer is expensive,
It is desired that the apparatus can be used effectively, but in reality, no effective measures have been taken to shorten the execution time of a synthesis protocol including a production reaction performed under temperature control.

The present invention has been made in view of the above circumstances, and has an automatic analyzer that can effectively use the apparatus by shortening the execution time of a synthesis protocol including a production reaction performed under temperature control. The purpose is to provide.

[0011]

The present invention has the following configuration to achieve the above object. That is, the invention according to claim 1 comprises a reaction block in which a plurality of reaction vessels for performing a production reaction are arranged, a reagent / solvent dispensing means for dispensing a reagent and a solvent into the reaction vessel, and a temperature of the reaction block. Temperature control means for controlling the temperature by raising the temperature to the target temperature and maintaining the temperature in the reaction vessel in which the reagent and the solvent are dispensed and supplied by the reagent and solvent dispensing means under the temperature control by the temperature controlling means. The temperature of the reaction block is raised to a predetermined preliminary temperature before the dispensing of the reagent and the solvent into the reaction vessel by the reagent / solvent dispensing means is completed in the automatic synthesizer configured to perform the It is characterized by having been constituted so that.

The invention according to claim 2 provides a reaction block in which a plurality of reaction vessels for performing a production reaction are arranged, a reagent / solvent dispensing means for dispensing a reagent and a solvent into the reaction vessel, Temperature control means for controlling the temperature by raising the temperature to the target temperature and maintaining the temperature, wherein the reagent and the solvent are dispensed by the reagent and solvent dispensing means, and the reagent and the solvent are dispensed and supplied under the temperature control by the temperature controlling means. An automatic synthesizing apparatus configured to perform a reaction, wherein a forced cooling means for forcibly cooling a reaction block is provided.

[Operation] According to the first aspect of the present invention,
By the time the dispensing of the reagent and the solvent to the reaction vessel by the reagent / solvent dispensing means is completed, the temperature of the reaction block is raised to a predetermined preliminary heating temperature, and the reagent and the solvent are dispensed to the reaction vessel. When the supply is completed, the temperature of the reaction block is preliminarily raised to a temperature higher than a predetermined temperature near normal temperature.

With this configuration, when the temperature of the reaction block is raised to the target temperature after the dispensing and supply of the reagent and the solvent to the reaction vessel is completed, the temperature at the start of the temperature rise of the reaction block is reduced. The temperature difference between the reaction block and the target temperature can be made smaller than before, so that the time required to raise the temperature of the reaction block to the target temperature after the dispensing and supply of the reagent and the solvent to the reaction vessel is completed. Can be reduced as compared with the conventional case.

The above "preliminary heating temperature" is a temperature within a range that does not affect the production reaction. Therefore, even if the temperature of the reaction block is raised to a predetermined preliminary temperature while the reagent and the solvent are being dispensed and supplied to the reaction vessel, no adverse effect is exerted on the production reaction.

According to the second aspect of the present invention, when the temperature of the reaction block is lowered from the target temperature, the reaction block is forcibly cooled by the forced cooling means. As a result, it is possible to reduce the time required for completing the production reaction and lowering the temperature of the reaction block from the target temperature as compared with the conventional apparatus that has been left to natural cooling.

[0017]

Embodiments of the present invention will be described below with reference to the drawings. FIG. 1 is a block diagram showing the overall configuration of an organic automatic synthesis apparatus according to one embodiment of the present invention, FIG. 2 is a plan view showing the configuration of a reaction system of the embodiment apparatus, and FIG. 3 is a reaction block of the embodiment apparatus. It is the schematic which shows the principal part structure of.

As shown in FIG. 1, the automatic construction apparatus of the embodiment comprises a reaction system in which an actual production reaction is performed and a control system which controls the movement of the reaction system. Hereinafter, the configuration of the reaction system of the example apparatus will be described first.

The apparatus of the embodiment is a reaction vessel 2 for performing a production reaction.
And a liquid dispensing unit 3 for dispensing a reagent and a solvent into a reaction vessel (reaction vessel) 2 in accordance with a preset dispensing procedure (dispensing protocol). Each reaction vessel 2 is, as shown in FIG.
The reaction blocks 1 are arranged in a matrix arrangement in a vertical and horizontal matrix. The number of reaction vessels 2 installed in the reaction block 1 is not limited to a specific number, but may be, for example, tens to hundreds of vessels such as 96 or 384. In the case of the example apparatus, the reagent and the solvent are dispensed and supplied to the reaction vessel 2 by a common dispensing mechanism, but the reagent and the solvent may be dispensed and supplied by different dispensing mechanisms. Good.

The liquid dispensing section 3 includes a syringe 4 and a syringe moving mechanism section 5 for moving the syringe 4 right and left (X), back and forth (Y), and up and down (Z), according to a command signal from the control system. The syringe moving mechanism 5 is operated to move the syringe 4 to a required position.

On the other hand, beside the reaction block 1, a large frequently used reagent container (frequently used reagent vial) 6 containing a large amount of used chemicals and the like, and a small common reagent containing a small amount of used chemicals and the like. A required number of containers (common reagent vials) 7 are provided. In addition, a solvent container (gallon bin) 8 containing a solvent is also provided in the reaction block 1.
The solvent containers 8 are connected to the syringes 4 by liquid feed lines 9, respectively.

When a chemical solution is dispensed and supplied to the reaction container 2, as shown by a dotted line in FIG. 1, the syringe 4 is placed at the position of the frequent reagent container 6 or the regular reagent container 7 containing the chemical solution to be dispensed. The syringe 4 is moved to the position of the reaction container 2 to be dispensed with the drug solution, and then the suctioned drug solution is injected into the reaction container 2 from the syringe needle 4a.

When the solvent is dispensed and supplied to the reaction vessel 2, the solvent is supplied from the solvent vessel 8 containing the solvent to be dispensed to the liquid sending line 9.
The solvent is introduced into the syringe 4 via the vial, and the syringe 4 is moved to the position of the reaction container 2 to be dispensed with the solvent,
The introduced solvent is injected into the reaction container 2 from the syringe needle 4a.

Usually, as described above, the syringe is moved so that the liquid is sucked at the position of the frequent reagent container 6 or the common reagent container 7 and the liquid is injected at the position of the reaction container 2. However, in the case of the apparatus of the embodiment, conversely, it is also possible to move the syringe 4 so that the liquid is sucked at the position of the reaction container 2 and the liquid is injected at the position of the frequent reagent container 6 or the common reagent container 7. Configuration.

In the case of the reaction block 1 of the embodiment, FIG.
As shown in FIG. 3, a sheet-shaped common septum 10 covering the inlet of each reaction vessel 2, and a pressurized transmission type filter 11 attached to each reaction vessel 2 so as to cover the inside of the bottom side of the reaction vessel 2, A drain 12 is provided for each reaction vessel 2 so as to communicate with the bottom of the reaction vessel 2, and a pressurized gas (for example, a high-pressure inert gas) from a gas cylinder GB is provided on the injection port side of the reaction vessel 2. ) Is provided. Therefore, when injecting a reagent or a solvent, the syringe needle 4a is connected to the common septum 1
Thus, the gas enters the reaction vessel 2 through 0.
In addition, an appropriate amount of range particles 14 for the solid phase reaction are respectively charged into each reaction vessel 2, and an on-off valve 15 is provided at the end of the gas introduction line 13. When the pressurized gas is introduced into the valve, the on-off valve 15 is closed.

Further, the apparatus of the embodiment is provided with a vibrating section 16 for oscillating the range particles 14 in each reaction vessel 2 by oscillating the reaction block 1 during the execution of the reaction generation. The reaction block 1 also includes a discharge tray 17 for discharging unnecessary substances generated in the container 2 and a collection block 18 for collecting the final compound obtained in each reaction container 2 by the production reaction for each reaction container 2. Is arranged so as to be movable between a lower position and a standby position.

Further, the reaction block 1 of the apparatus of the embodiment is provided with an electric heater HT for heating the reaction block 1 and three temperature sensors TS. Electric heater H
T is configured to supply heat to the reaction block 1 according to a drive signal sent from the control system side. The temperature sensors TS are separately installed in the reaction block 1, and each temperature sensor TS sends the measured temperature to the control system in the form of an electric signal.

The apparatus of the embodiment is also provided with a forced cooling unit CU for forcibly cooling the reaction block 1. For example, as shown in FIG. 4, the forced cooling unit CU includes a cooling water supply device 30 for producing and supplying cooling water at a predetermined temperature (for example, an arbitrary temperature of 0 ° C. to 8 ° C.), and A cooling pipe 31 provided, a supply pipe 32 for guiding cooling water from the cooling water supply device 30 to one end of the cooling pipe 31, and a cooling pipe 31.
And a return pipe 33 for returning the water discharged from the other end of the cooling water supply device 30 to the cooling water supply device 30.
Is flowed in one direction, heat of the reaction block 1 is absorbed by the cooling water CW flowing in the cooling pipe 31, and is discharged out of the reaction block 1 to forcibly cool the reaction block 1. The water heated by the heat of the reaction block 1 returned to the cooling water supply device 30 via the return pipe 33 is cooled to a predetermined temperature in the cooling water supply device 30 and sent out to the supply pipe 32. And configured to reuse the cooling water.

In FIG. 4, a bypass pipe 34 for flowing the cooling water sent to the supply pipe 32 to the return pipe 33 without passing through the cooling pipe 31 is provided near the reaction block 1. An on-off valve 35 provided on the pipe 34;
Of the supply pipe 32, an on-off valve 36 provided on the cooling pipe 31 side with respect to a branch portion with the bypass pipe 34, and the return pipe 33 provided on the cooling pipe 31 side with respect to the connection part with the bypass pipe 34. Check valve 37 for preventing the cooling water flowing from the bypass pipe 34 to the return pipe 33 from flowing back to the cooling pipe 31.
And In this configuration, when the temperature of the reaction block 1 is not lowered, the on-off valve 35 is opened and the on-off valve 36 is closed, and cooling water is circulated through the supply pipe 32, the bypass pipe 34, and the return pipe 33, When the temperature of the reaction block 1 is started, the on-off valve 35 is closed and the on-off valve 36 is opened, so that the cooling water flows into the cooling pipe 31. For example, at the start of the temperature reduction of the reaction block 1,
The cooling water supply device 30 may be configured to start supplying the cooling water from the cooling water supply device 30. However, since the cooling water supply device 30 is usually installed at a location away from the reaction block 1, such a configuration is adopted. In this case, a loss time occurs before the cooling water actually starts flowing through the cooling pipe 31. On the contrary,
In the configuration shown in FIG. 4, even when the temperature of the reaction block 1 is not lowered, the cooling water is circulated to the vicinity of the reaction block 1. This contributes to shortening the temperature drop time of the reaction block 1.

The operation of the cooling water supply device 30 and the opening and closing valve 35,
The opening / closing control of 36 is executed by a drive signal sent from the control system side.

In FIG. 4, switching between a state in which the cooling water flows through the cooling pipe 31 and a state in which the cooling water flows through the bypass pipe 34 is performed by controlling the opening and closing of the on-off valves 35 and 36. A three-way valve may be provided at a branch portion between the pipe 32 and the bypass pipe 34, and by switching control of the three-way valve, the cooling water may be switched between a state of flowing the cooling water to the cooling pipe 31 and a state of flowing the cooling water to the bypass pipe 34. Good.

Further, for example, the cooling water flowing through the bypass pipe 34 and the cooling water discharged from the cooling pipe 31 are connected to the cooling water supply device 30 directly without connecting the distal end of the bypass pipe 34 to the return pipe 33. Cooling water supply device 3
The pipe may be returned to zero.

Further, in FIG. 4, the water discharged from the cooling pipe 31 is returned to the cooling water supply device 30. For example, the water discharged from the cooling pipe 31 is discarded and discarded. The cooling water supply device 30 may be configured to replenish the water that has been collected.

In the production reaction process by the automatic synthesis apparatus of the embodiment, the solid phase reaction proceeds in the range particles 14 of each reaction vessel 2 into which necessary reagents and solvents are dispensed and supplied, and the target compound is formed. can get. In the drainage process performed after the generation reaction, the pressurized gas in the gas cylinder GB is introduced from the gas introduction line 13, and the reagents and the solvent in each reaction vessel 2 are transmitted through the pressurized transmission filter 11 to the drain 12. It is pushed down to the discharge tray 17 and discharged. Also, when the last production reaction is completed and the last dispensed reagent or solvent is discharged,
An extraction (acid) chemical solution for taking out the compound generated inside the range granules 14 is fed from the inlet of each reaction vessel 2. Then, when the compound is extracted, the pressurized gas in the gas cylinder GB is introduced from the gas introduction line 13, and the compound is passed through the pressurized transmission filter 11 together with the extracting chemical solution and flushed from the drain 12 to the collection block 18. To recover the compound.

Next, the configuration of the control system of the embodiment will be described. The automatic synthesizing apparatus according to the embodiment includes a video display monitor 19 for displaying various screens necessary for operating the apparatus, a control unit 20 for executing various controls necessary for operating the apparatus in a timely manner, and a keyboard for input operation. (Operation console) 2
1 and a mouse (pointing device) 22 as well as a characteristic configuration for shortening the heating time and the cooling time of the reaction block 1 when performing the production reaction under temperature control. Hereinafter, this characteristic configuration will be specifically described mainly.

The control section 20 of the embodiment apparatus dispenses a drug and a solvent set in advance by a screen display section 23 for displaying a screen necessary for the operation of the apparatus on a video display monitor 19 and an input operation by a keyboard 21 and a mouse 22. A dispensing control unit 24 for sending a command signal for dispensing according to a procedure (dispensing protocol) to the liquid dispensing unit 3 is provided.

The procedure for dispensing the reagent and the solvent to each reaction vessel 2 is configured to be set using the keyboard 21 and the mouse 22 in accordance with an appropriate setting screen displayed on the video display monitor 19. When executing the synthesis protocol, a command signal is sent from the dispensing control unit 24 to the liquid dispensing unit 3 in accordance with the set dispensing procedure.

The control section 20 has a solvent database 25 for storing solvent data such as a solvent name (kind) and a boiling point. This solvent database 25
Registration and deletion of data to the solvent database 25
Of the registered contents of the keyboard 21 and the mouse 22 in accordance with an appropriate setting screen displayed on the video display monitor 19.
It is constituted so that it can be performed using.

Further, the control unit 20 is installed in the reaction block 1 and a target temperature holding unit 26 for holding a target temperature at the time of the generation reaction in the reaction block 1 which is set in advance by an input operation of the keyboard 21 and the mouse 22. A drive signal is sent to the electric heater HT based on the average value of the actually measured temperatures sent from the three temperature sensors TS, and the temperature of the reaction block 1 is raised to a preliminary heating temperature described later during the dispensing process. And a temperature adjusting unit 27 for adjusting the temperature of the reaction block 1 to the target temperature held in the target temperature holding unit 26 after the dispensing step is completed. . Electric heater HT and temperature sensor TS on the reaction system side, and target temperature holding unit 2 on the control system side
6 and the temperature adjusting unit 27 constitute a temperature adjusting unit in the present invention.

When a plurality of production reactions are performed, whether or not to perform the temperature control for each production reaction can be set by an input operation of the keyboard 21 and the mouse 22. It is configured such that a target temperature for each production reaction performed under temperature control can be maintained.

The control unit 20 further includes a cooling control unit 28 for sending a drive signal to the forced cooling unit CU. The cooling control unit 28 terminates the production reaction performed under the temperature control, and cools the reaction block 1 when the reaction block 1 is cooled.
U, a drive signal is sent to the cooling block 31 in the reaction block 1 in the configuration shown in FIG.
Is configured to be forcibly cooled. The forced cooling unit CU on the reaction system side and the cooling control unit 28 on the control system side constitute a forced cooling unit in the present invention.

In addition to the above-described procedures, conditions, and the like, if there are procedures, conditions, and the like necessary for executing one synthesis protocol, the settings are made using the keyboard 21 and the mouse 22. It is configured as follows.

In addition to the control for the reaction system-side components described above, if there is control for the reaction system-side components required to execute one synthesis protocol, the control unit 20 controls the reaction system-side components. It is configured to be.

The configuration of the control system of the above-described embodiment apparatus is built around a personal computer and software (computer program).

Next, the operation of the embodiment apparatus having the above configuration will be described. As shown in the flowchart of FIG. 5, one synthesis protocol includes a dispensing process (step S1), a production reaction process (step S2), and a drainage process (step S1).
When the final production reaction is completed by performing 3) one or more times (Step S4), a filtration step of recovering the finally obtained compound is performed (Step S5). In each dispensing process,
Reagents and solvents set for each dispensing step are dispensed to each reaction vessel 2. In addition, in each generation reaction step, vibration (stirring) of range particles 14 by vibrating section 16 and temperature adjustment section 2 are performed in accordance with the conditions set for each generation reaction step.
7, the temperature of the reaction block 1 is also controlled.

Next, a dispensing step using the apparatus of the embodiment when the production reaction is performed while the temperature of the reaction block 1 is controlled,
The operations of the production reaction step and the drainage step will be described with reference to a time chart shown in FIG.

First, for example, at the same time as the dispensing by the liquid dispensing section 3 is started, the temperature adjusting section 27 adjusts the temperature of the reaction block 1 to a predetermined temperature Tb near normal temperature (for example, 25 ° C.).
Then, the operation of raising the temperature to the predetermined preliminary temperature raising temperature Ts is started. In other words, at the same time as the start of the dispensing, the temperature adjusting unit 27 performs the electric control so that the temperature difference between the average value of the actually measured temperatures sent from the three temperature sensors TS and the preliminary heating temperature Ts becomes “0”. A drive signal is sent to the heater HT. And
When the temperature of the reaction block 1 reaches the pre-heating temperature Ts, the temperature of the reaction block 1 is raised to the pre-heating temperature until the dispensing and supply of the reagent and the solvent to each reaction vessel 2 is completed (the dispensing step is completed). Maintain at Ts.

The “preliminary heating temperature Ts” is a temperature within a range that does not affect the production reaction.
Assuming that the target temperature of the reaction block 1 at the time of the production reaction held in the target temperature holding unit 26 is Tt, the target temperature is determined by the following equation.

Ts = Tb + ((Tt−Tb) / 2)

Further, the boiling point of the solvent dispensed into each reaction vessel 2 for performing the production reaction under temperature control is taken out from the solvent database 25, and the following boiling point (Tf) is used for the solvent. The preliminary heating temperature Ts may be determined by an equation.

Ts = Tb + ((Tf−Tb) / 2)

Next, when the dispensing and supply of the reagent and the solvent to each reaction vessel 2 is completed (the dispensing step is completed), the temperature adjusting section 27 sets the temperature of the reaction block 1 to the target temperature holding section 26.
Then, the operation of raising the temperature to the target temperature Tt held at the start is started. That is, the temperature adjustment unit 27 includes three temperature sensors T
The temperature difference between the average value of the measured temperatures sent from S and the target temperature Tt held in the target temperature holding unit 26 is “0”.
A drive signal is sent to the electric heater HT such that
When the temperature of the reaction block 1 reaches the target temperature Tt held in the target temperature holding unit 26, the temperature of the reaction block 1 is held in the target temperature holding unit 26 for a preset reaction time. The production reaction is performed while maintaining the target temperature Tt and controlling the temperature to the target temperature.

When the temperature of the reaction block 1 is
When the reaction time elapses after the target temperature Tt held at 6 has been reached and the production reaction step is completed, the temperature adjusting unit 27
Stops the sending of the drive signal to the electric heater HT, and the cooling control unit 28 sends the drive signal to the forced cooling unit CU so as to perform the forced cooling of the reaction block 1.

When the average value of the measured temperatures (the temperature of the reaction block 1) sent from the three temperature sensors TS reaches a predetermined temperature Tb near normal temperature, the cooling control unit 28 reacts to the forced cooling unit CU. A drive signal for stopping the forced cooling of the block 1 is transmitted. Thereafter, a drainage step is performed.

As described in detail above, according to the automatic synthesizing apparatus of this embodiment, the reaction block 1 is kept at the pre-heating temperature Ts before the dispensing and supply of the reagent and the solvent to each reaction vessel 2 is completed. When the temperature of the reaction block 1 is raised to the target temperature Tt held in the target temperature holding unit 26 after the dispensing supply of the reagent and the solvent to each reaction vessel 2 is completed, The temperature difference between the temperature at the start of the temperature rise of the reaction block 1 and the target temperature Tt can be made smaller than before, and after the dispensing and supply of the reagent and the solvent to the reaction vessel 1 is completed, the reaction block 1 The time required to raise the temperature to the target temperature Tt can be reduced as compared with the conventional case. It is preferable that the temperature of the reaction block 1 has reached the pre-heating temperature Ts at the time when the dispensing and supply of the reagent and the solvent to each reaction vessel 2 is completed. Even when the temperature of the reaction block 1 has not reached the preliminary temperature rise temperature Ts at the time when the dispensing and supply of the reaction block 1 is completed, the temperature of the reaction block 1 is higher than the predetermined temperature Tb near normal temperature. Since the temperature difference between the temperature at the start of the temperature rise of the reaction block 1 and the target temperature Tt is smaller than before, the dispensing and supply of the reagent and the solvent to the reaction vessel 1 are completed. The time required to raise the temperature to the target temperature Tt can be reduced as compared with the conventional case.

As described above, the "preliminary heating temperature T
Since “s” is a temperature within a range that does not affect the production reaction, the temperature of the reaction block 1 is raised to the pre-heating temperature Ts during the dispensing and supply of the reagent and the solvent to each reaction vessel 2. This does not adversely affect the production reaction.

Further, according to the automatic synthesizing apparatus of this embodiment, the mechanism for forcibly cooling the reaction block 1 (forcibly cooling unit C)
U and the cooling control unit 28), it is possible to shorten the time required for completing the production reaction and lowering the temperature of the reaction block 1 from the target temperature Tt as compared with the conventional apparatus which is left to natural cooling. .

FIG. 6B is a time chart showing the operations of the dispensing process, the production reaction process, and the drainage process by the conventional apparatus when the production reaction is performed while the temperature of the reaction block 1 is controlled. As is clear from the comparison between FIG. 6A and FIG. 6B, according to the automatic synthesis apparatus of this embodiment, the temperature of the reaction block 1 is increased by t1 and the temperature of the reaction block 1 is decreased by t2. It is possible to shorten the time required for subtracting the time te required for cooling the reaction block 1 by the apparatus from the time tp required for cooling the block 51 from the time tp required for the temperature reduction of the reaction block 1, and to generate the reaction under the temperature control of the reaction block 1. If you do,
The time from the start of the dispensing step to the end of the draining step can be shortened by (t1 + t2) as compared with the conventional apparatus. Therefore, the execution time of the synthesis protocol including the production reaction performed under temperature control can be shortened as compared with the conventional apparatus, and effective use of the expensive automatic analyzer can be achieved.

When the production reaction is continuously performed under the temperature control, for example, as shown in FIG.
When the temperature of the reaction block 1 is lowered after the completion of the production reaction of (2,...), The temperature of the reaction block 1 becomes equal to the target temperature Tt2 (or the (n + 1) th dispensing step) in the (n + 1) th production reaction. The temperature is lowered until the temperature reaches the preliminary temperature rising temperature Ts2 determined by the boiling point of the dispensed solvent).
Sets the temperature of the reaction block 1 to the above-mentioned preliminary heating temperature Ts2 during the n-th draining step and the (n + 1) -th dispensing step.
By the end of the (n + 1) th dispensing step, the temperature of the reaction block 1 is raised to a predetermined preliminary temperature rising temperature Ts2.
The temperature may be increased. With this configuration, when the temperature of the reaction block 1 is lowered after the n-th generation reaction is completed, the temperature of the reaction block 1 is further reduced in time than when the temperature of the reaction block 1 is once lowered to the predetermined temperature Tb near normal temperature. Can be shortened.

The present invention is not limited to the above embodiment, but can be modified as follows.

(1) In the apparatus of the embodiment, a structure for raising the temperature of the reaction block 1 to a predetermined pre-heating temperature before the dispensing and supply of the reagent and the solvent to each reaction vessel 2 is completed. And a configuration for forcibly cooling the reaction block 1, but may be configured to include only one of the configurations.

(2) In the description of the embodiment, the reaction block 1
Has been described to start the operation of raising the temperature of the reaction block 1 to the preliminary heating temperature Ts at the same time as the dispensing by the liquid dispensing unit 3 is started. However, the temperature of the reaction block 1 is raised to the preliminary heating temperature Ts. The operation may be started before or after the start of dispensing.

(3) In the embodiment, the reaction block 1 is forcibly cooled by using cooling water. However, the reaction block 1 is cooled by using a cooling medium other than cooling water such as liquid nitrogen.
May be configured to be forcibly cooled, may be configured to be air-cooled using a cooling gas, or may be configured to forcibly cool the reaction block 1 by absorbing heat of the reaction block 1 by a Peltier element. You may comprise.

(4) In the embodiment, three temperature sensors T
Although the temperature control and the like are performed by averaging the measured temperatures of S, the temperature control and the like may be performed by selecting the highest temperature among the measured temperatures of the three temperature sensors TS. Further, the number of temperature sensors provided in the reaction block 1 is not limited to a specific number, and may be, for example, one.

(5) In the apparatus of the embodiment, one set of the reaction system was used. However, as a modified example, an apparatus having a configuration in which two sets of the same reaction system controlled by one set of the control system are provided. Can be

(6) Example The apparatus was an automatic organic synthesis apparatus, and a compound was synthesized by a solid phase reaction. However, the apparatus of the present invention may be an inorganic automatic synthesis apparatus. Alternatively, an apparatus having a configuration in which a compound is synthesized by a liquid phase reaction may be used.

[0067]

As is apparent from the above description, according to the first aspect of the present invention, the reaction and dispensing of the reagent and the solvent to the reaction vessel by the reagent and solvent dispensing means are completed. Since the temperature of the block is configured to be raised to a predetermined preliminary heating temperature, when the dispensing supply of the reagent and the solvent to the reaction vessel is completed, when the temperature of the reaction block is raised to the target temperature, The temperature difference between the temperature at the start of the temperature rise of the reaction block and the target temperature can be made smaller than before, and after the dispensing of the reagent and the solvent to the reaction vessel is completed, the temperature of the reaction block is raised to the target temperature. The time required to raise the temperature can be shortened as compared with the conventional case. Therefore,
The execution time of a synthesis protocol including a production reaction performed under temperature control can be shortened, and an expensive automatic analyzer can be effectively used.

According to the second aspect of the present invention, since the forced cooling means for forcibly cooling the reaction block is provided, the time required for finishing the production reaction and lowering the temperature of the reaction block from the target temperature is reduced by the conventional method. Can be shortened. Therefore, it is possible to shorten the execution time of the synthesis protocol including the production reaction performed under temperature control, and it is possible to effectively use an expensive automatic analyzer.

[Brief description of the drawings]

FIG. 1 is a block diagram showing the overall configuration of an automatic organic synthesis apparatus according to one embodiment of the present invention.

FIG. 2 is a plan view showing a configuration of a reaction system of the apparatus of the embodiment.

FIG. 3 is a schematic diagram showing a configuration of a main part of a reaction block of the apparatus of the embodiment.

FIG. 4 is a diagram illustrating a configuration of an example of a forced cooling unit.

FIG. 5 is a flowchart showing the flow of each step when executing one synthesis protocol.

FIG. 6 is a time chart showing operations of a dispensing process, a production reaction process, and a drainage process by the apparatus of the embodiment and a conventional apparatus when a production reaction is performed while the temperature of the reaction block is controlled.

FIG. 7 is a time chart showing a modification of raising and lowering the temperature of the reaction block by the apparatus of the embodiment when the production reaction is performed while the temperature of the reaction block is controlled.

FIG. 8 is a schematic diagram showing a configuration of a main part of a conventional automatic synthesis apparatus.

[Explanation of symbols]

 1: reaction block 2: reaction vessel 3: liquid dispensing unit 24: dispensing control unit 26: target temperature holding unit 27: temperature adjusting unit 28: cooling control unit HT: electric heater TS: temperature sensor CU: forced cooling unit

Claims (2)

[Claims] 1. A reaction block in which a plurality of reaction vessels for performing a production reaction are arranged, a reagent / solvent dispensing means for dispensing a reagent and a solvent into the reaction vessel, and the temperature of the reaction block is raised to a target temperature. Temperature adjusting means for adjusting the temperature to be maintained by maintaining the temperature and the temperature of the reaction vessel in which the reagent and the solvent are dispensed and supplied by the reagent and solvent dispensing means. In the automatic synthesizer, the temperature of the reaction block is raised to a predetermined preliminary temperature before the dispensing of the reagent and the solvent into the reaction vessel by the reagent / solvent dispensing means is completed. An automatic synthesizing apparatus characterized by the above-mentioned. 2. A reaction block in which a plurality of reaction vessels for performing a production reaction are arranged, reagent / solvent dispensing means for dispensing a reagent and a solvent into the reaction vessel, and raising the temperature of the reaction block to a target temperature. Temperature adjusting means for adjusting the temperature to be maintained by maintaining the temperature and the temperature of the reaction vessel in which the reagent and the solvent are dispensed and supplied by the reagent and solvent dispensing means. An automatic synthesizing apparatus, further comprising a forced cooling means for forcibly cooling the reaction block.