MXPA01003849A

MXPA01003849A - Porous device

Info

Publication number: MXPA01003849A
Application number: MXPA/A/2001/003849A
Authority: MX
Inventors: Ryszard Kobylecki
Original assignee: Cambridge Combinatorial Limited
Priority date: 1998-10-14
Filing date: 2001-04-11
Publication date: 2002-06-05

Abstract

A porous device for use in a method of synthesis comprising a body having an internal region which is porous wherein an active material, for example a solid support resin, is entrapped within the internal region.

Description

DEVICE POROUS BRIEF DESCRIPTION OF THE INVENTION This invention relates to a porous device. Preferred embodiments relate to the use of a porous device or porous devices for example, in a synthesis method (especially a parallel arrangement "mixing and incision", or combined method); a porous device per se; and a method of manufacturing a porous device. The use of solid supports in the synthesis of compounds, for example peptides or any other types of chemical compounds, is well known. A particularly important contribution to this field is made in 1963 by Merrifield who describes the preparation of spherical styrene-divinyl benzene beads for use in synthesis. A wide range of other functionalized beads have been proposed since then, as it has methods and devices to handle beads and / or use them in the automated synthesis of compound libraries. For example, beads have been provided in the form of "tea bags". A more sophisticated format uses porous reusable tubes in which resin samples are weighted, for example as described in W096 / 36436 (see for example Figure 14). Disadvantageously, the tubes are expensive and in addition, they need to be loaded with carefully weighed samples of resin being loaded with carefully weighed samples of resin that can be time consuming. In addition, the tubes by themselves generally have an internal volume which is significantly greater than the volume of the resin incorporated in the tubes, thus allowing for the expansion of the resin (up to 3 or 4 times its original volume) in solvents with which the tubes can be contracted in synthesis procedures. It is an object of the present invention to address the problems described in the foregoing. According to a first aspect of the present invention, there is provided a method of synthesis using a porous device comprising a body having an internal region which is porous, wherein an active material is trapped within the internal region. Preferably, in the method, a covalent bond is formed between the active material and a reagent (or a fragment thereof) used in the synthesis. Preferably, the method includes the step of contacting such a porous device with a first reagent under conditions that cause the first reagent to react with the active material, such that a bond, preferably a covalent bond, is formed between the material active and the first reagent (or a fragment thereof). Preferably, the method further includes contacting the porous device with a second reagent under conditions that cause a second reagent to react with the first reagent (or a fragment thereof) to bind to the active material. As a result, the second reagent (or a fragment thereof) can be attached, preferably covalently linked, to the first reagent (or a fragment thereof). In this manner, the preferable manner involves contacting, preferably sequentially, the porous device with reagents (eg, a first reagent, a second reagent, etc.) to prepare a compound which is covalently bound to the active material of the reagent. porous device. In this way, it preferably involves contacting the porous device with at least two, preferably at least three, more preferably at least four, reagents wherein each reagent interacts with one of either the active material and / or a portion attached to the active material, to facilitate the realization or destruction of the covalent bonds. The active material preferably includes a functional group which is not inert, but which is reactive. For example, the functional group is preferably capable of reacting in nucleophilic or electrophilic reactions. The active material is preferably arranged to act as a support for a compound prepared in solid phase synthesis. The active material is preferably not a catalyst (and / or is not a function as a catalyst in the method) to catalyze the gas phase solution or reactions. The active material preferably includes a functional group selected from a chloromethyl group, hydroxymethyl or aminomethylated or a derivative thereof. The active material can include a linker or can be covalently linked to a linker in the synthesis, for example in a first step thereof, wherein the linker comprises a portion in which a compound that is prepared in the synthesis is linked during its synthesis and where after the preparation of the compound, it can be divided from the active material by breaking a bond between the connector and the compound. The methods of providing connecting portions are well known. Examples are provided in Tetrahedron Vol. 51, No. 30, pages 8135 to 8173 (1995) (the contents of which are incorporated herein by reference) and may include Wang, Rink and Trityl Linkers. In this way, the method preferably includes the step of dividing a compound prepared from the active material. The divided compound can then be isolated. In the method, the active material can be contacted with at least two, suitably at least three, preferably at least four, more preferably at least five, different compounds (which term includes any solvents or reagents) prior to the stage of division. The internal region is preferably unitary. The internal region is preferably monolithic. The inner region preferably does not include a plurality of different layers of material. Suitably, the material which makes the inner region is / are fixed at the position of the inner region. The arrangement and / or position of the active material (e.g. particles thereof) is preferably predetermined. The material or materials are preferably fixed in position by means within the internal region. The inner region of the body preferably has a predetermined shape. The predetermined form can be varied, for example because of the internal region that is flexible. However, the shape of the inner region is preferably substantially fixed. The internal region is preferably non-flowable, for example at 25 ° C. The internal region suitably comprises a random network of pores which preferably have a substantially fixed configuration and which suitably extends through substantially the total of the internal region. The active material is preferably distributed through substantially the entire inner region. The pore network is preferably not defined by a fabric and / or filaments and / or a fibrous material. The inner region preferably does not include a fabric and / or filaments and / or a fibrous material. The inner region is preferably coupled by fluid passages from one side of the opposite side thereof. Substantially the entire inner region is porous. Preferably, the porosity of the internal region is substantially constant throughout its extension. Preferably, the void volume of the internal region is substantially constant throughout its extension. The void volume of the internal region may be at least 20%, suitably at least 30%, preferably at least 40%, more preferably at least 45%, especially at least 48%. The void volume may be less than 80%, suitably less than 70%, preferably less than 60%, more preferably less than 55%, especially 52% or less. The inner region may substantially or continuously extend, in a first direction from an outer wall of the porous device in an opposite outer wall thereof. The inner region may substantially or continuously extend in a second direction (perpendicular to the first direction) from an outer wall of the porous device in an opposite outer wall thereof. The region may substantially or uninterruptedly extend in a third direction (perpendicular to the first and second directions) from an outer wall of the porous device to an opposite external wall thereof. Alternatively, an opening, for example a housing region, can be defined within the body of the porous device which allows the region to extend from an external wall of the porous device to an opposite external wall thereof. For example, when the porous device is cylindrical, it may have an end open cylindrical housing region extending in the direction of the cylinder axis. The provision of an opening as described can increase the surface area of the inner region which can be brought into contact with the fluid in the synthesis method. In this case, the shape of the inner region can be selected to maximize the available surface area for example it can have a star shape or with many curves. In another situation, the opening can be arranged to accommodate an identification means as described in the following. Preferably, the internal region includes at least one sinterable material. The sinterable material can be a thermoplastic. The inner region preferably includes at least one sinterable material. The sinterable material preferably defines the porous structure of the inner region. The internal region may have a dimension in a first direction of at least 1 mm, suitably at least 2 mm, preferably at least 3 mm, more preferably at least 4 mm, especially at least 5 mm. The internal region may have a dimension in a second direction, perpendicular to the first direction, of at least 1 mm, suitably of at least 2 mm, preferably at least 3 mm, more preferably at least 4 mm. mm, especially at least 5 mm. The inner region may have a dimension in a third direction, perpendicular to the first and second directions, of at least 1 mm, suitably at least 2 mm, preferably at least 3 mm, more preferably at least less 4 mm, especially at least 5 mm. Preferably, at least one (more preferably two, especially three) of the first, or second or third directions is / are coincident with a respective axis of symmetry of the internal region. The porous device preferably has a predetermined shape. The porous device can be flexible. However, the shape of the porous device is preferably fixed. The porous device suitably comprises a random network of pores that preferably have a substantially fixed configuration. The porous device is preferably not of an interleaved construction or layer. In this way, it is preferable not to include a plurality of different layers of the material. This preferably comprises a simple unitary material (which itself can be made from a mixture of one or more components) that is, the porous device is preferably substantially monolithic. The porous device is preferably prepared by a fluid passage in a first direction on one side of an opposite side thereof. In this way, the pores of the inner region adequately open on the surfaces or the device. Preferably, the porous device is prepared for the passage of fluid in a second direction, perpendicular to the first direction, on one side of an opposite side thereof. Preferably, the porous device is prepared for the passage of the fluid in a third direction, perpendicular to the first and second directions, the shape of a side of a porous side thereof. Preferably, the porous device is freely porous in three mutually perpendicular directions. Suitably, at least 50%, preferably at least 75%, more preferably at least 90%, especially at least 95% of the surface of the device is porous. More preferred is the case where substantially the total outer surface of the device is porous. Preferably, the porosity of the porous device is substantially constant throughout its extension. Preferably, the void volume of the porous device is substantially constant throughout its extension. The void volume of the porous device can be at least 20%, suitably at least 30%, preferably at least 40%, more preferably at least 45%, especially at least 48%. The void volume may be less than 80%, suitably less than 70%, preferably less than 60%, more preferably less than 55%, especially 52% or less. Preferably, the porosity on a surface of the device is substantially the same as the porosity of the adjacent region of the surface. Preferably, some active material is on or adjacent to the surface of the porous device and is suitably in a fixed position relative to the surface. The porous device preferably does not include any fabric and / or filaments and / or fibrous material. The porous device can be provided in any desired form and, more particularly, in any form that has been proposed to be used as a solid support in the solid support reactions. For example, the device may be in the form of a cylinder, rod, blade, capsule, tablet, plug, disc, filament or cap. The preferred shapes have a smaller dimension of at least 1 mm, suitably at least 2 mm, preferably at least 3 mm, more preferably at least 4 mm, especially at least 5 mm. Preferred forms of the device include cylinders, rods, capsules, tablets or stoppers. Any porous device may include an attachment, for example a hook, opening (or the like) to allow the device to be removed and positioned, preferably robotically. An especially preferred form of a porous device can be as described in W096 / 36436 (for example see Figure 14) and the described forms are incorporated herein by reference. Advantageously, the use of the aforementioned forms may allow devices to be used to manipulate the porous device. The porous device is preferably and substantially self-supporting. The porous device is preferably substantially rigid. In one embodiment, the porous device can be provided in a sheet form that is used to support a multiplicity of point synthesis. Preferably, however, the device is not a sheet. The porous device may have a dimension in a first direction of at least 1 mm, suitably at least 2 mm, preferably at least 3 mm, more preferably at least 4 mm, especially at least 5 mm. The dimension in the first direction can be less than 100 mm, suitably less than 80 mm, preferably less than 50 mm, more preferably less than 30 mm, especially less than 10 mm. The porous device may have a dimension in a second direction, perpendicular to the first direction of at least 1 mm, suitably at least 2 mm, preferably at least 3 mm, more preferably at least 4 mm, especially by at least 5 mm The dimension in the second direction can be less than 100 mm, suitably less than 80 mm, preferably less than 50 mm, more preferably less than 30 mm, especially less than 10 mm. The porous device may have a dimension in a third direction, perpendicular to the first and second directions, of at least 1 mm, suitably at least 2 mm, preferably at least 3 mm, more preferably at least 4 mm , especially at least 5 mm. The dimension in the third direction can be less than 100 mm, suitably less than 80 mm, preferably less than 50 mm, more preferably less than 30 mm, especially less than 10 mm. Preferably, at least one (more preferably two, especially three) of first, second or third directions is / are coincident with a respective axis of symmetry of the porous device. In the inner region preferably complete at least 30%, suitably at least 50%, preferably at least 70%, more preferably at least 90%, especially at least 95%, of the volume of the porous device . The volume of the internal region is preferably substantially equal to the shape as the volume of the porous device. The porous device (suitably the internal body region) may have a volume of at least 25 mm 2, preferably at least 50 mm 2, preferably at least 100 mm 2, more preferably at least 150 mm 2, especially by at least 200 mm2. The volume may be less than 10000 mm2, suitably less than 5000 mm2, preferably less than 2500 mm2, more preferably less than 10000 mm2, especially less than 500 mm2. The porosity of the device with methanol at room temperature and the pressure may be at least 0.2 ml / minute, suitably at least 0.4 ml / min, preferably at least 0.6 ml / min, especially at least 0.8 ml / min. The porosity can be less than 1.5 ml / min, preferably less than 1 ml / min. The porous device can include at least 10 μmol, suitably at least 25 μmol, at least preferably at least 40 μmol, more preferably μmol of the functionality suitable for participation in the synthesis. The internal region of the porous device, for example pores thereof, can be defined by the active material so that, appropriately, the internal region can consist essentially of active material. The active material may comprise a single material or a plurality of different active materials may be included. Such a porous device can be referred to in the following as a "first type" of the porous device. Another type of porous device, in the following referred to as a "second type" of the porous device, may comprise an inert material (in the sense that it is not covalently bound to a compound synthesized in the method) and an active material. The inert material can be prepared within the pores of the porous support means. Preferably, the active material is not covalently bound to the porous support means. Preferably, the majority (eg greater than 50%, suitably greater than 60%, preferably greater than 70%, more preferably greater than 80%, especially greater than 90%) of the active material is exposed (i.e. not covered by the inert material) so that the majority of the active material is available for the binding formation in the synthesis. Preferably, the active material is in the form of a multiplicity of active material is in the form of a multiplicity of individual particles, wherein the particles are separated from one another by the inert material and, appropriately, are maintained in substantially fixed positions relative to each other and / or in relation to the inert material. The individual particles of the active material can be separated from each other at a distance of at least 50 μm, suitably at least 70 μm, preferably at least 90 μm, more preferably at least 110 μm, especially at least minus 120 μm. The particles can be separated from one another by a distance of less than 1000 μm, suitably less than 600 μm, preferably less than 400 μm, more preferably less than 200 μm, especially less than 150 μm. The aforementioned distance between the suitable particles represents the pore burn of the internal region. The active material is preferably held in place by a physical weld suitably provided by the inert material. Preferably, the inert material defines a random network in which the active material is embedded. The active material preferably includes an accessible functionality so that covalent bonds can be formed between these and the reagents used in the synthesis. The active material can include at least 10 μmol, suitably at least 25 μmol, preferably at least 40 μmol, more preferably at least 55 μmol, especially at least 70 μmol of accessible functionality. In some situations, for example where the porous device is of the second type described, the active material by itself is preferably porous and includes the accessible functionality within its internal structure. In this way, preferably, the formation of the covalent bonds between the active material and the reagents used in the synthesis not only takes place on a surface of the active material, but also takes place within a solid portion of active material, by example within a use of active material count. Suitably, the active material includes a functional group capable of participating in (preferably the non-free radical) chemical reactions. For example, the active material may include a leaving group. Preferably, the active material is polymeric and is more preferably an organic polymeric material, for example a resin. The active material is preferably a crosslinked resin. The active material is preferably in the form of beads. The active material is preferably non-cellulosic. The resin can be a polystyrene-based resin (for example a substituted alkyl (for example methyl or ethyl) polystyrene, an aminomethylated polystyrene, a benzyloxybenzyl alcohol resin, a carboxypolystyrene, a polystyrene-divinylbenzene copolymer, a trityl chloride, a trityl resin, a phenoxy resin, a dihydropyran resin, a Merrifield resin, a formyl polystyrene, a benzydrylamine resin, an oxime resin, a polystyrene-based resin (PEG) or a resin of polyethylene glycol acrylamide (PEGA). The active material can be substituted methyl polystyrene, for example, chloromethyl polystyrene, hydroxy methyl polystyrene or amino methyl polystyrene or a derivative of any of the aforementioned which incorporate a linker. Alternatively, the active material can be a substituted polypropylene (or another optionally substituted polyalkylene polymer). Such a polymer can be substituted with a haloalkyl, especially a chloromethyl group or the active material can be a derivative of such a group that incorporates a linker. The active material can be a material which, in isolation, is expandable in organic solvents. The known active materials can expand from three to five times their original volume in the solvents. However, advantageously, when incorporated into a porous device as described herein, the active material is conserved and can not significantly expand. As a result, the external shape of the porous device can be substantially unchanged, even during or after the device has been contacted with a solvent in which the active material should normally expand. In addition, the size of the device can be substantially unchanged. In this regard, the maximum dimension of the device (for example the length where the device is a cylinder) and / or any dimension may change by less, less than 80%, suitably less than 60%, preferably less than 40%, more preferably less than 20%, especially less than 10%, after the device has been submerged, for up to 1 hour, and a solvent in which the active material should normally expand. When the porous device includes an inert material, the inert material suitably does not participate in the chemical reactions in the synthesis. For examplepreferably, it does not include a leaving group. The inert material can be organic or inorganic. The inert material is preferably non-cellulosic. The inert material is preferably a sinterable material. The inert material is suitably sinterable at a temperature of less than 500 ° C, preferably less than 400 ° C, more preferably less than 300 ° C, especially less than 200 ° C. The inert material is preferably a sinterable material. The inert material is preferably a thermoplastic. Examples of organic material include organic polymeric materials which are suitably resins and may include, for example, optionally substituted, preferably unsubstituted, polyalkylenes (especially polyethylene and polypropylene), and polyhaloalkylenes (especially polyfluoroalkylenes such as polytetrafluoroethylene). The active material is preferably a ground material. The particles of active material can be substantially spherical. The active material can have size particles in the range of 10 μm to 100 μm. The porous device can include at least % by weight, suitably at least 20% by weight, preferably at least 30% by weight, more preferably at least 40% by weight, especially at least 45% by weight of the active material. The amount of active material may be less than 90% by weight, suitably less than 80% by weight, preferably less than 70% by weight, more preferably less than 60% by weight, especially less than 55% by weight. To avoid doubt, the aforementioned weight percent of the active material refers to the total amount of all the active materials in the porous device. In some situations described in the following, a porous device may include more than one type of active material. The porous device may include at least 10% by weight at least, suitably at least 20% by weight, preferably at least 30% by weight, more preferably at least 40% by weight, especially at least 4S% by weight of the inert material. The amount of inert material may be less than 90% by weight, suitably less than 80% by weight, preferably less than 70% by weight, more preferably less than 60% by weight, especially less than 55% by weight. To avoid doubt, the aforementioned weight percent of inert material refers to the total amount of inert material in the porous device and includes a situation where more than one type of inert material is included. The porous device may include a filler or fillers. The fillers can be colored and the different porous devices can include different colors that allow to distinguish the different porous devices from each other. Preferably, the porous device consists essentially of the active material and the inert material. The porous device suitably passes at least one, preferably any, most preferably all, of the following tests: Test 1 - The porous device is boiled in methanol. The device passes the test if it is exchanged after 10 minutes of boiling minutes. Tests 2 to 7 - These are the same as in Test 1 except that the solvents are ethanol, 1,4-dioxane, water, DMSO, DCM, and THF respectively. Test 8 - The porous device is heated in DMF to 120 ° C in an oil bath. The device passes the test if it is exchanged after 10 minutes of treatment. Test 9 - The porous device is heated in DMF and centrifuged at 1300 r.p.m. The device passes the test if it is exchanged after 10 minutes of treatment. The porous device suitably is capable of withstanding any one, preferably any selection, most preferably all of the following reactions: a Suzuki reaction, a Mitsunobu reaction, oxidation of alcohol using pyridine sulfur trioxide in DMSO and reduction of a aldehyde in an alcohol using sodium cyanoborohydride. According to a second aspect of the invention, there is provided a method of synthesizing a plurality of different compounds, the method using a plurality of porous devices as described according to the first aspect and including contacting a first porous device with a first sequence of reagents and contacting a second porous device with a second sequence of reagents wherein the first and second sequences of the reagents are different, thereby preparing different compounds in the first and second. The first sequence of the reagents may comprise reacting the first porous device with, for example, an a-amino ester hydrochloride followed by a reduction and cyclization reaction, followed by an alkylation reaction using an alkyl bromide. The second sequence may be different from the first using an a-amino ester hydrochloride or an alkyl bromide. Preferably, the method according to a second aspect is a method of synthesizing different compounds N, where N is a positive integer, using porous devices N, the method includes using different N sequences of reagents and contacting the porous devices with a respective sequence so that they prepare different respective compounds in the porous devices. The integer N may be 4 or greater, suitably 10 or greater, preferably 20 or greater, more preferably 24 or greater. In some situations, N may be 50 or greater, suitably 100 or greater, preferably 200 or greater, more preferably 500 or greater, especially 1000 or greater. Advantageously, the method can be used in any parallel order, "mixing and division" or combined techniques. More particularly, the method can be combined. More particularly, the method can be used in techniques described in, for example, W096 / 36436. Preferably, the porous devices used in the method are, initially, substantially identical. The devices, however, preferably include means of identification (or cue) to chemically identify the devices from each other. The identification means may comprise, for example numbers, letters, symbols or colors in the coded combination, Smiles cords, bar code, chemical structures, punched card formats by marking or printing, readable ultraviolet devices, or any other readable device, such as magnetic tapes. In some embodiments, the identification means may comprise a magnetically readable electronic device, for example a device ready to be read by a transmitter Rf or a magnetic-readable device. The identification means preferably include an identifier, preferably a coded identifier, ready to be read by a reading form or device. The identifier preferably includes a unique code. The identity of the identifier and / or information associated with the identification means may be predetermined and / or not changeable after the identification means have been associated with the device. In accordance with a third aspect of the present invention, the use of a porous device as described according to the first aspect in the synthesis of a compound. The invention extends to the use of a plurality of porous devices as described according to the second aspect in the synthesis of a plurality of compounds. According to a fourth aspect of the present invention, there is provided a method for affecting an interaction between an active material and another material (hereinafter an "interaction material"), the method using a porous device comprises a body that It has an internal region which is porous, where the active material is trapped within the inner region. Preferably, the method comprises the juxtaposition of the active material and the interaction material suitably in a fluid. The porous device of the fourth aspect may include any feature of a porous device described in any statement herein. The method can be to affect a chemical interaction between the active material and the interaction material. The active material can be adapted to sweep The active material can be adapted to sweep the interaction material from a fluid that contacts the interaction material. Suitably, the method includes the step of contacting the porous device with a fluid containing the material, suitably sweeping the fluid to maximize contact between the interaction material and the device and, suitably, substantially eliminating the porous device to from the fluid after the active material of the device has swept the interaction material. Advantageously, the method can not involve filtering the fluid contacting the interaction material (i.e., provides the porous device or the porous devices in a fluid flow path of the fluid so that all pass through the porous device) so it obviates the need to handle the volume of the fluid by itself. However, in some embodiments, the porous device or devices can act as active filters so that the active interaction material interacts with material that is being filtered. The active material can be prepared to have an affinity for the interaction material. The active material may have an affinity for particular metals, radioactive wear, resins, magnetic compounds or portions, acids or bases.

The active material can be a catalyst. The active material can be chemical or biological. The active material may be adapted to interact with cells or enzymes, suitably so that it immobilizes the cells or enzymes for subsequent use. The active material can be a reagent which is coupled to interact with the interaction material and therefore causes a chemical reaction, preferably the formation of covalent binding, with the interaction material. The method according to the fourth aspect may use a porous device which includes at least two different active materials trapped within the inner region. The active materials may be as described in any of the statements herein. Advantageously, the porous device can incorporate two active materials which must contact each other in a fluid to be reactive with one another; however, using such a porous device, the two active materials are spaced apart and therefore prevented from the reaction. Where a porous device includes at least two different active materials, at least two materials can comprise two materials selected from reagents, sweepers or catalysts. For example, a porous device may include a reagent and a scavenger; or two different sweepers or reagents, etc. The method can involve the porous device to which it is being placed in a column (or similar) whose fluid can flow. Advantageously, the column can include at least two different types of porous device (i.e., the different contact of the active materials) which can be prepared to define a mixed bed in the column or can be prepared sequentially. The devices can, properly, be disks formed for use in a column. Advantageously, the separate porous devices that include active materials which must, if contacted with one another in a fluid be reactive with each other that can be used without damage even if the porous devices contacted one another. The column described can use a filtration. Alternatively, it can be used in the synthesis of continuous flow, so that, appropriately, the column is sequentially packed with porous devices adapted to interact with the material in the stages of the synthesis. In another embodiment, a plurality of porous devices can be prepared in an order. Each porous device can include a different active material and each active material can be prepared to interact with the different interaction material. The order can then be used for affinity purification. Preferably, the order is a combined mixing order. According to a fifth aspect of the present invention, there is provided a porous device comprising a body having an internal region that is porous, wherein an active material is trapped, suitably substantially immobile, within the internal region. The porous device may be as described in any statement herein. This preferably comprises inert or co-sintered active materials. Preferably, the active material is prepared to act as a support for a compound prepared in a solid phase synthesis. Preferably, the active material includes a connector. Preferably, the porous device includes a synthesized compound or a fragment thereof covalently bound to the active material, for example the connector, and ready to be cut from the device. Where the device is in the form of a sheet material, a plurality of different compounds can be covalently attached to the device, for example, as a result of point synthesis, suitably in spaced apart positions. The porous device preferably includes an identification means associated therewith, for example being substantially permanently fixed to a part of the device. According to a sixth aspect of the invention, there is provided a porous device comprising an active material which, in isolation, is dilated in an organic solvent, and a prepared restriction medium restricts the expansion of the active material in the organic solvent. The solvent may be a methanol, ethanol, 1,4-dioxane, water, DMF, DMSO, DCM, or TF. The restriction means can be of any type that can restrict the expansion of the active material, suitably at least 50%. However, the porous device can be of the second type described herein and the restriction means can be provided by the inert material. According to a seventh aspect of the present invention, a placement or assembly comprising a plurality of porous devices according to the fifth or sixth aspects is provided. Preferably, each porous device includes a unique identification means. A unique identification means is preferably provided even for porous devices incorporating the same type of active material. Preferably, the identification means allows each porous device to be distinguished from each porous device in the placement or assembly. The placement or assembly may include at least 10, suitably at least 50, preferably at least 100, more preferably at least 1000, especially at least 5000 porous devices. The plurality of porous devices can be prepared randomly or prepared in an array that can suitably be a dimensional or two dimensional. The means to fix each porous device in the arrangement can be provided and this can simply comprise members strung together. Such an arrangement may be prepared and / or manipulated, for example in the preparation of a library of compounds, as described in the co-pending PCT Application Application No. PCT / GB98 / 03875 or in W096 / 16078 (Pfizer) and the contents of the mentioned documents are incorporated herein by reference. The invention extends to a placement or assembly as described herein wherein the devices support a plurality of different compounds, suitably with a compound that is supported by the device. Preferably, a library of different compounds is supported by the devices. According to an eighth aspect of the present invention, there is provided a method of sintering a library of compounds, the method using a plurality of porous devices according to the fifth or sixth aspects and suitably includes the step of subjecting each porous device to a unique sequence of treatments and / or reactions, so prepare different compounds in the porous devices. The method may also include the step of dividing the synthesized compounds from the devices. According to a ninth aspect of the present invention, there is provided a method for making a porous device for use as described in any statement herein, the method comprising causing a body having a porous internal region to form with an active material. stuck with it. The porous devices of the first type described above can be made by mixing a material which is to define the active material, suitably a powder form, with a removable poroformation material.; forming the mixture in a desired form; causing the agglomeration of the mixture, for example sintering (or otherwise heating) the mixture, optionally under applied pressure; and, so it eliminates the pore formation material. The material of pore formation can be eliminated causing its decomposition. Such a pore forming material can be calcium carbonate. Alternatively, the pore forming material can be removed by dissolution, for example by contacting the agglomerated mixture with a solvent. Such a pore-forming material can be sodium chloride which can be removed by dissolving in water. This will be appreciated that the amount of the pore forming material relative to the active material can be adjusted, thereby adjusting the porosity of the porous device. The material which is to define the active material of the first type of porous device is preferably thermoplastic and / or preferably sinterable. In some situations, a porous device of the first type can be prepared by synthesizing the ground active material in the absence of a pore forming material. It may be possible to prepare a porous device of the first type, wherein the material which is to define the active material is functionalized after the preparation of the porous structure, by which it defines the active material. Such functionalization can affect graft radiation, for example as described in PCT / GB98 / 03875. However, it is preferred that the material which is to define the active material is an active material prior to the preparation of the porous structure (and the material does not need to be post-functionalized to make it into an active material); for example, it may be a resin having functionality which functionality it can provide in a polymeric material by suitable means, for example, radiation grafting as described. A particularly preferred material of this type can be polypropylene which has been grafted radiation to define the functionality therein. The porous devices of the second type described in the above may, in one embodiment, be made by mixing inert material, suitably in powder form, with the active material, suitably in the powdered form; forming the mixture in a desired form; and causing agglomeration of the mixture, for example sintering (or otherwise heating) the mixture, suitably in a mold, optionally under pressure. The sintering / heating is preferably carried out at a temperature below the melting point (and / or at a low temperature to that at which the flow starts) of the active material. The sintering / heating is preferably carried out at a temperature no lower than the softening temperature of the inert material and no higher than the decomposition temperature thereof. The sintering / heating preferably takes place at or about (for example within 10% of) the melting point of the inert material. In this way, preferably, in general terms, the porous devices of the second type are made by co-sintering a mixture of an inert material and an active material. In another embodiment, the porous devices of the second type can be made by in situ polymerization, in the presence of the active material, of the monomers to provide, when polymerized, the inert material, whereby the foam is affected during the polymerization and the The process is such that the active material becomes distributed through the foamed inert material. In a further embodiment, porous material may be impregnated with an active material and, optionally, the steps may be taken to immobilize the active material within the device. The method of the ninth aspect may include causing an active material which includes a connector as described herein to be trapped. Either the connector can be an integral part of the active material used in the preparation of the porous device or a porous device that includes an active material that can be post-functionalized to provide the connector. Where the method is to make a porous device according to the fourth aspect, this may be advantageous for post-treating a device manufactured as described herein by providing a desired active material in the device. A preferred method for manufacturing any porous device described herein which includes an active material and an inert material involves the co-sintering of a mixture comprising particles of the active material and the inert material, thereby providing a monolithic structure. The method may be of particular utility where the active material is of a type described according to the first aspect or is a catalyst (suitably to catalyze a solution phase reaction) or is a solid support reagent, suitably where the Reagent is for use in a solution phase reaction. The inert material is preferably a thermoplastic. In an exemplary embodiment, the present invention relates to a method of preparing new materials suitable for use as substrates in the solid phase chemistry, and materials obtained herein. The method of preparing the new materials involves the process of co-sintering a chemically active species that supports or contains accessible functionality with a variety of materials that form the matrix. The materials that form the matrix can additionally, by themselves, support the functionality chemically. The sintering method may be as follows: An intimate mixture of an organic or inorganic matrix that forms material and a number of chemically active species, which support or contain accessible functionality, is first formed into an appropriate physical form. The new mixture is then sintered or co-sintered by subjecting it to a variety of temperature for a variable residence time according to the melt flow characteristics of the matrix that forms the material. A unique identifier can, if necessary, be incorporated during training, or applied before manufacturing. Support materials that can be co-sintered include, without limitation: polystyrene-based resin beads of the type included in the following, polypropylene-based materials such as resin beads and powders, chemically modified beads and powders, zeolites, beads of Teflon or any organic and inorganic powder or beads that will allow chemical or physical union to its inner surface of the chemical reagents. active or molecules. A selection of suitable support materials for sintering include: Oxime resin, Wang resin, NovaSyn TB aminoresin, Wang p-nitrophenyl carbonate resin, Aminomethyl-NovaGel HL, 2-chlorotritylchloride resin, 3,5-Dimethoxy-4- polystyrene formyl-phenoxyethoxy-methyl, LL Merrifield resin, Zeolites, molecular sieves 5A, 4A, 3A, 2A, montmorillonite clay powder and Amberlista. The co-sintered matrix that forms the materials may include, without limitation, any organic or inorganic matrix that forms the material of appropriate melt flow characteristics such as to allow formation by means of physical bonding or containment of the detailed support materials. previously. This includes, without limitation, polyethylene, polypropylene, per halo-polyalkylenes and other suitable chemical and physical materials. The materials of the type described are suitable, in the various forms for chemistry, as follows: - in the solid phase chemistry where the support may be the resin beads trapped from matrix including in the same or the matrix by itself . - for use in the solution phase chemistry where the substrates in the solution can be introduced to react together with a reagent or number of reagents trapped in or chemically bound to a solid phase, by themselves trapped without the matrix. The matrix itself may also have a reagent or number of reagents trapped or chemically bound to its surface. to catalyze several chemical reactions by means of the occluded reagents trapped inside, for example a matrix of the inorganic zeolite, itself trapped within the sintered matrix, or the matrix itself may be the catalyst. The exemplary embodiment includes the possibility of sintering an existing polymer material in powder or bead form, which by itself has been chemically or physically modified, to allow attachment or entrapment of active chemical species on or within the surface of the powder form or count in new physically reinforced forms. This includes, without limitation, cylinders, rods, sheets, capsules, tablets, plugs, filaments, tapes, etc. The modality allows the incorporation of a unique identifier at the point of manufacture of new sintered physical forms or the subsequent identification in manufacturing. This includes, without limitation, indication which only characterizes each reaction zone. The indicia may comprise, for example, numbers, letters, symbols or colors in a coded combination. The clue can be applied to the respective reaction zones before the synthesis begins using known printing methods.

These are preferably such that the ink used will not bleach from the reaction zones during synthetic procedures, or otherwise, interfere with the information and subsequent removal of a compound maintained in a particular reaction zone. UV-sensitive ink that is "fixed" to the reaction zones by exposure to ultraviolet radiation after printing is generally suitable for this purpose. Other types of clues, not necessarily optical in nature, can be used to identify individual reaction zones. Possible alternatives include Smiles series, barcode, chemical structures, punched card formats by marking or printing, readable ultraviolet fluorescent systems and electromagnetically readable devices such as magnetic tapes and RF ID, dot matrix reading of snowflakes and other analogous systems. The type of indicia used may depend on the size and shape of the support material and / or the reaction zones. An additional principle is that of one or more layers of the reagent containing matrices that can be simultaneously or subsequently formed or reformed to provide a material that contains 2 or more reagent matrices within the same physical format that allows 2 or more reactions to proceed at the same time or subsequently within the same matrix. Any feature of any aspect of any invention or embodiment described herein may be combined with any feature of any aspect of any other invention or embodiment described herein. The specific embodiments of the invention will now be described, by way of example, with reference to the appended figures, wherein: Figure 1 is a schematic representation of a porous plug; Figure 2 is a line II-II along the transverse section of Figure 1; Figure 3 is an electromicrograph of a section through the plug in a first amplification; and Figure 4 is an electron micrograph of a section within box III of Figure 2, at a higher amplification. The porous plug 2 of Figures 1 and 2 comprises an inert carrier and a functionalized resin which has been sintered together under pressure in a molding to define a self-supporting rigid cylindrical structure which has substantially constant density and porosity through its extension. The plug can be used in many applications, for example in the synthesis of chemical compounds that can inert define a matrix that physically supports or supports the functionalized resin spheres in fixed spaced positions, there are no covalent bonds formed between the functionalized resin and the inert carrier . It will also be noted that the internal structure of the plug is very porous and that substantially all of the surface area of the functionalized resin spheres is freely exposed (ie not covered with the inert carrier) so that most of the functionalized resin is available by subsequent chemical reactions. A range of plugs (A to J) has been made using the general procedure described above and incorporating one of the functionalized resins detailed in Table 1. be covalently bound to the functionalized resin. Additional details are provided in the following. A typical process for manufacturing a plug 2 involves blending micronized ultra high molecular weight polyethylene (to provide the inert carrier) and beads (e.g., particle diameters in the range of 10-lOOμm) of a functionalized resin. The ratio of the weight percent weight of the polyethylene in the functionalized resin is suitably about 1. The polyethylene mixture and the resin is put into a mold made of aluminum alloy, taking care to ensure consistent packing of the mold. The mold is then placed in an oven and sintered at 190 ° C for 20-25 minutes in the ambient atmosphere. After removing the mold from the oven, it is allowed to cool and the stopper is then moved away from the mold. While any size or shape of stopper can be produced, the cylinder produced and used as described herein has a diameter of 6mm, a height of 9mm and a volume of 255mm2. Such plugs are specifically made for use in 96 well plates that are conventionally used in organic synthesis. In the electromicrographs of Figures 3 and 4, the spheres are the functionalized resin and the material between the spheres in that inert carrier. It will be noted that the carrier It has been found, in general, that the described plugs can be used in any situation where the functionalized resin can be used since the plugs are physically and chemically stable and the functionalized resin can be accessed by reagents. The examples of treatments / reactions undertaken using the plugs are described below. Example 1 Samples from each of the plugs A to J are boiled for 10 minutes in each of the following solvents: methanol, ethanol, 1,4-dioxane, water, DMF (test undertaken using an oil bath at 120 ° C ), DMSO, DCM and THF. The plugs are subsequently examined and found to be exchanged for the treatment. Example 2 Samples from each of the plugs A to J are suspended in DMF and centrifuged for 10 minutes at 13,000 r.p.m. The plugs are changed again by the treatment. Example 3 Ten different pre-charged resins (PS and PS-PEG's) and a range of different connectors (for example, Wang and formyl Trityl couplers on an oxime-based support) are prepared in the form of the stopper. Its synthetic utility was demonstrated in comparison to the identical lots of resin of functionality lost under a load range, synthesis and division procedure. In all cases, the products isolated after division from the functionalized resin of the stoppers, in terms of purity and yield, are compared to those of the resin released. Example 4 A wide range of solid phase chemistries of typical literature are carried out in plugs A to J. These vary from the formation of aminomethyl and the Wang resin from the chloromethyl resin (Plug E), chemicals from Suzuki, reductive aminations, reductions, oxidations, acylations, esterifications, 1,3-dipolar additions, SN-displaced synthesis and benzodiazepine. In all cases, the little adaptation (if any) of the synthetic synthetic resin protocols are needed. Example 5 = Derivatization of resin Chloromethane-styrene (LL Merryfield resin) to Aminomethyl resin A plug of chloromethylene Merrifield resin (78μmol) (Stopper E) was suspended in dry DMF (10 ml). The potassium phthalimide (10ec) was added and the reaction was gently stirred at 120 ° C for 24 hours. The stopper was washed with hot DMF (5x 5ml), DMF: H20 (1: 1, 5x) 5ml), dioxane: H20 (1: 1, 5x 5ml), MeOH (5x 5ml), DCM (5x) 5ml), and ether (5x 5ml). The stopper was then suspended in ethanol (lOml), hydrazine hydrate (2ml) was added and the reaction was refluxed for 4 hours. Then it was washed like in the previous thing and it was analyzed to give a substitution of 55. 8μmol (71% conversion based on a manufacturer's load). Example 6 - Preparing a Fmoc-Rink Connector Layered of Resin-bound Acid The encapsulated aminomethylated polystyrene resin (1 stopper, 55.8μmol) prepared in Example 5, previously dilated in DCM, was treated with a solution of p- acid. { (R, S) - (- [1- (9H-Fluoren-9-yl) -methoxyformamide] -2,4-dimethoxybenzyl] -phenoxyacetic acid (1.5ec), DIC (1.5ec) and HOBt (1.5ec) in DCM (5ml) and the reaction stirred for 48 hours.The stopper was washed with DCM (5x 5ml), DMF (5x 5ml), MeOH (5x 5ml), and Et20 (5x 5ml) (hereinafter referred to as " the usual wash cycle. ") The remaining free amino sites are capped with excess acetic anhydride / pyridine in DCM The stopper was again washed according to the usual wash cycle and a quantitative Fmoc test gave a substitution of 40μmol ( 75% render.) Example 7 - Derivatization of Chloromethyl Resin with a Wang Connector A plug of Chloromethyl Resin Merrifield (78μmol) (Stopper E) was suspended in acetonitrile (10 ml). 4-Hydroxybenzaldehyde (0.2g, 1.6 mmol), K2CO3 (0.4g, 1.6 mmol) was added followed by sodium iodide (0.24g, 1.6 mmol). The mixture was refluxed for 48 hours. The stopper was washed according to the usual wash cycle and then suspended in MeOH (5ml). Sodium cyanoborohydride (10 ec) was added to the gently stirred reaction. A piece of green bromocresol was added to the monitor, the pH is maintained by periodic addition of 10% HCl in ethanol (one or two drops once). After 16 hours, the plug was washed to proceed to the derivatized resin with the Wang connector. Example 8 - Preparation of Fmoc-Fe-Gli-OH The derivatized plug Wang prepared in Example 7 reacts with Fmoc-Gly-OH (0.3 g, 1 mmol), DIC (1 mmol), DMAP (0.1 mmol) in DCM (10 mL) for 24 hours. After washing, a quantitative Fmoc test gives a substitution of 20μmol. The plug is then coupled to Fmoc-Phe-OH (0.4 mmol), DIC (0.4 mmol) and HOBt (0.4 mmol) in DCM for 24 hours. After washing, the plug was treated with 95% TFA and the crude product analyzed by HPLC reveals the desired dipeptide [ES-MS m / z = 445 (M + H)] as the main compound only. Example 9 - Preparation of the Tripeptide Fmoc-Ala-Phe-Glv-NH, A plug of the Fmoc-Rink Example 6 was treated with 20% piperidine in DMF for 20 minutes. After the usual wash cycle, Fmoc-Gly-OH (5ec), HOBt (5ec) and DIC (5ec) was added and the allowed coupling proceeded for 4 hours in DCM (lOml). Some precipitation was observed as the reaction proceeded and 1 ml of DMF was added to give a clear solution. After the usual wash cycle and the removal of the Fmoc group, the analogous procedure was used to couple Fmoc-Phe-OH and then Fmoc-Ala-OH to obtain the Fmoc-Ala-Phe-Gly-Rink linker resin. The tripeptide is then divided from the resin by stirring with 95% TFA for 1 hour. The volatiles are removed under vacuum and the crude tripeptide purified by the semi-prepared HPLC to provide 10.4 mg of the pure product (63% yield). The product was identical to that obtained in the ordinary polystyrene beads. Example 10 - Suzuki Experiment Three plugs of the Fmoc-Rink linker resin of Example 6 (120μmol) in the total were treated with 20% piperidine in DMF for 20 minutes. After the usual washing cycle, Fmoc-Gly-OH (5ec), HOBt (5ec) and DIC (5ec) in DCM / DMF (20 / 2ml) was added. The reaction was stirred for 6 hours. A ninhydrin test was negative. The Fmoc group was removed and the resulting amino product was coupled to 4-iododobezoic acid (5ec), DIC (5ec) and HOBt (5ec) in DCM (20ml). The reaction was stirred for 18 hours. After washing, the stoppers were dilated in DMF (20ml) for 30 minutes. To this was added phenylboronic acid (1.5 ec), Pd [P (Ph) 3] 4 (0.1 ec) and K2C03 (2ec). The mixture was delicately stirred and heated at 100 ° C for 24 hours. The plugs were made black, but they were washed well using the usual washing cycle. The plugs were then treated with 95% TFA. HPLC analysis of the crude revealed the desired product (80% pure) which was purified and isolated (51% yield). Example 11 - Mitsunobu Experiment Two resin plugs of the Fmoc-Rink connector of Example 6 (80μmol in total) was treated with 20% piperidine in DMF for 20 minutes. After the usual washing cycle, Ac-Tyr-OH (5ec), HOBt (5ec) and DIC (5ec) were added and the coupling allowed to proceed for 6 hours in DCM / DMF (20 / 2ml). The stoppers were washed according to the usual wash cycle by drying THF (5x) and then suspended in dry THF (10 ml). Triphenylphosphine (5ec) was added followed by dry benzyl alcohol (10ec). Then, diethyl azodicarboxylate (5ec) dissolved in dry THF (5ml) was added in five portions at 5 minute intervals. After 2 hours, the plugs were washed according to the usual washing cycle. Division with 95% TFA and analysis of the crude product by HPLC revealed two components, which were separated in semi-prepared HPLC. The main component (42% yield) had the required molecular mass as shown by ES MS. This also co-eluted with the same product prepared in the polystyrene beads in the same way. Example 11 - Oxidation Experiment Two stoppers of Fmoc-Rink connector resin of Example 6 (80μmol in total), was treated with 20% piperidine in DMF for 20 minutes. After the usual wash cycle, Fmoc-Phe-OH (5ec), HOBt (5ec) and DIC (5ec) were added and the allowed coupling proceeded for 6 hours in DCM (20ml) After removing the Fmoc group, the same procedure was used to couple 4- (hydroxymethyl) benzoic acid. A plug was treated with 95% TFA to provide the starting material. The second plug was suspended in dry DMSO (10 ml) and to this was added pyridine sulfur trioxide (10 ec), triethylamine (10 ec), and the reaction was stirred for 18 hours. After the usual washing cycle, and dividing with 95% TFA, the unpurified solution was analyzed on HPLC to reveal the complete conversion in the aldehyde product (confirmed by ES MS and co-elution with an authentic sample, 53% yield ). Example 12 - Reduction Experiment Two resin plugs of Fmoc-Rink connector of Example 6 (80 μmol in total) was treated with 20% piperidine in DMF for 20 minutes. After the usual washing cycle, Fmoc-Phe-OH (5ec), HOBt (5ec) and DIC (5ec) were added and the allowed coupling proceeded for 6 hours in DCM (20ml) After removing the Fmoc group, the same procedure was used to couple 4-carboxybenzaldehyde acid. A plug was treated with 95% TFA to provide the starting material. The second plug was suspended in MeOH (lOml) and treated with sodium cyanoborohydride (lOec). A trace of bromocresol green was added to the flow of the reaction. An acidic medium (yellow color) was maintained by periodically adding 10% HCl in ethanol (one or two drops). After 4 hours, the stopper was washed according to the usual washing cycle and then divided with 95% TFA. HPEC analysis of incomplete conversion revealed without purification. The trace showed a peak corresponding to the initial aldehyde, the cyanohydrin and the desired alcohol product. All were separated in HPLC semi-prep. Alcohol yield 44%. Example 13 - Ease of washing the encapsulated polystyrene resin A stopper of the type prepared in Example 5 (55.8μmol) and an equivalent amount of TentaGel aminomethyl resin beads were treated separately with two equivalents of bromophenol blue DCM ( lOml). The materials converted the blue color of the same intensity to the eye. The two materials were washed in parallel with equal volumes of 10% triethylamine in DCM. The TentaGel resin required 5 washes (lOml each) to convert them into colors while the encapsulated resin of Example 5 required 12 washes. Similarly, the resins were treated with two equivalent of methyl red and washed in the same manner. The TentaGel resin required 3 washes to become colorless while the encapsulated resin of Example 5 required 5 washes. Example 14 - Preparation of Fmoc-Phe-NH-OH A plug of the resin derivatized with Rink acid (40μmol) was suspended in dry DCM. The reaction was gently stirred and a freshly prepared solution of 1% HCl in DCM / THF (3: 1) (9ml) was added slowly. The plug was then washed with DCM (2x), THF (2x), and DCM (2x). The stopper was immediately suspended in DCM (10 ml) and then Fmoc-NH-OH (1.5ec) and DIEA (1.5ec) was added and the reaction was allowed to stir for 24 hours. After washing the stopper according to the usual wash cycle, the Fmoc group was removed and the resulting amino compound was coupled to Fmoc-Phe-OH (5ec), DIC (5ec), and HOBt (5ec). The coupling was left for 24 hours. The plug was washed and then treated with 5% TFA / DCM to provide the carboxylic acid Fmoc-Phe-NH-OH (51% yield, 68% pure). Example 15 - Preparation of Ac-NH-CH.Ph A plug of 3, 5-dimethoxy-4-formyl-phenoxyethoxy-methyl polystyrene resin (dlμmol) (ie Plug B) was suspended in dry trimethyl orthoformate (6 ml ). Benzylamine (10ec) was added and the reaction stirred gently 70 CC for 3 hours. The plug was then washed with dry DMF (3x) and dry MeOH (3x). It was then suspended in dry MeOH (5ml) and reacted with NaBH4 (5ec) for 24 hours. The plug was carefully washed with MeOH (5x) and DCM (5x). Then acetylated with acetic anhydride / pyridine in DCM for 3 hours. After washing, it was partitioned with 25% TFA / DCM for 1 hour to provide the title compound (50% yield, 80% pure). Example 16 - Preparation of p-CH2-C ¿H ^ CH.-CO-NH- A plug of the resin 2-chlorotritilchloride (97μmol) (ie, Cap C) reacted with 1,3-diaminopropane (10 ec) in DCM for 24 hours. It was then washed and coupled to p-toliacetic acid (5ec), DIC (5ec), HOBt (5ec) in DCM for 6 hours. After washing, the stopper was treated with 50% TFA in DCM to provide the title compound (49%, 70% pure). Example 17 - Library of 20 3, -Displaced-7-carbamoyl-1, 2,3, 4-tetrahydrosuinoxalin-2-ones: (i) Binding of 4-Fluoro-3-n-trobenzoic acid to the Rink 20 Amide Amide Resin Fmoc-Rink plug resin plugs (40μmol each) was prepared in Example 6, treated with 20% piperidine in DMF for 20 minutes. The stoppers were washed with DMF (3x), MeOH (3x), DCM (3x), and Et20 (3x) and dried in vacuo. DIPEA (5ec in lOml of DCM) followed by 4-fluoro-3-nitrobenzyl chloride (5ec, in lOml of DCM, was prepared freshly by reaction of the acid with oxalyl chloride) to the dry plugs. . The reaction was gently stirred for 6 hours after which a ninhydrin test was negative. (ii) General Procedure for the Aromatic Substrate of Aryl Fluoride with a-amino Esters The twenty plugs were divided into four groups (five plugs each). Each group was then added equivalents of a-amino ester hydrochloride (L-alanine methyl ester, L-leucine methyl ester, L-phenylalanine methyl ester, and L-phenylglycine methyl ester), 20 equivalents of DIPEA and 10 ml of DMF at room temperature. The suspensions were shaken for 3 days. The supernatants were removed and the plugs were washed as above and dried. (iii) General Procedure for Reduction of Arilo Ni Group and Cyclization Five equivalents of SnCl2.2H20 and 10 ml of DMF were added to each group of five plugs. The suspensions were shaken for 3 days. The supernatants were removed and the resins were washed as above and dried. (iv) General Procedure for Alkylation at the N-4 position of Quinoxalinone with Alguyl Halides To each plug of each group of the cyclized resins was added 25 equivalents of alkyl bromide [benzyl bromide, 4-nitrobenzyl bromide, 2- (bromomethyl) naphthalene, 4-methylbenzyl bromide and methyl 4- (bromomethyl) benzoate], 25 equivalents of K2C03 and 2ml of acetone. The 20 reactions then heated up to 55 ° C for 48 hours. The stoppers were then washed with acetone (3x), H20 (3x), DCM (3x), and Et20 (3x) and then dried in vacuo. (v) General unfolding procedure 5 ml of 95% TFA was added to each stopper and the mixture was allowed to stir for 1 hour. The supernatants were separated and the plugs were washed with MeOH (3x2ml). The combined supernatants were concentrated and the unpurified products were analyzed by HPLC and MS. Example 18 - Library of 25 Biarilo Derivatives (i) Twenty-five plugs of the Fmoc-Rink connecting resin (40μmol each) was prepared in Example 6, treated with 20% piperidine in DMF for 20 minutes. The plugs were washed with DMF (3x), MeOH (3x), DCM (3x), and Et20 (3x) and dried, in vacuo. The plugs were divided into five groups (five plugs each). Add to each group in DCM / DMF (20 / 2ml) 5 equivalents of one of one of five iodo-aryl carboxylic acids, (4-iodobenzoic acid, 3-iodo-4-methylbenzoic acid, 2-iodohippuric acid, acid 4-iodophenylacetic acid and 4-iodophenoxyacetic acid), DIC (5ec), and HOBt (5ec). The reactions were stirred for 24 hours. The stoppers were thoroughly washed with DMF (5x), DCM (5x), MeOH (5x), and Et20 (5x). Each plug of each group was dilated separately in 3 ml of dry DMF. Then 1.5 equivalents of one of five boronic acids (phenylboronic acid, 4-metipheniboronic acid, 3-acetylphenylboronic acid, 4-methoxyphenylboronic acid, and thiopene-2-boronic acid), Pd [P (Ph) 3] were added to each stopper. "(O.lec), and K2C03 (2ec). The reactions were heated at 100 ° C for 24 hours. The plugs were washed with hot DMF (5x), MeOH (5x), DCM (5x), and Et20 (5x). (ii) Cleavage and Analysis To each plug was added 5ml of 95% TFA and the mixture was left to stir for 1 hour. The supernatants were separated and the resins were washed with MeOH (3x2ml). The combined supernatants were concentrated and the unpurified products were analyzed by HPLC and MS. Example 19 - 24 Pyrrolidine Library Substituted (i) Union of the Wang Connector Twenty-four caps of the aminomethylated polystyrene resin (55.8μmol / plug) prepared in Example 5 were dilated in DCM / DMF (50 / lOml). To these was added 5 equivalents of 2- [4- (hydroxymethyl) phenoxy] acetic acid, DIC (5ec), and HOBt (5ec). The mixture was stirred for 24 hours. The stoppers were then washed with DMF (5x), MeOH (5x), DCM (5x) and Et20 (Sx). (ii) Union of Amino Acids The plugs were divided into four groups (6 plugs each). Each group then reacted with 5 equivalents of one of four Fmoc-amino acid acids (Fmoc-Gly-OH, Fmoc-Ala-OH, Fmoc-Leu-OH, and Fmoc-Phe-OH), D1C (5ec), and DMAP ( O.lec). The reactions were left for 24 hours.

The plugs were then washed carefully as in the above. (iii) Formation of Aryl Imines bound to Resin The plugs of each group were treated separately with 20% piperidine in DMF for 20 minutes. They were washed as above and dried in vacuo. Each group of plugs at the time were divided into three lots (2 plugs each); in this way 12 separate reactions. Each batch was suspended in 1% dry AcOH / DMF (4ml) and to this was added lOec from one of three aldehydes (benzaldehyde, o-toldehyde, and 2-methoxybenzaldehyde). The untreated amines in the stoppers were capped with an excess of Ac20, DIPEA in DCM for one hour. The plugs were washed carefully and dried. (iv) 1, 3 Dipolar Cycloaddition of Azometin Iridides attached to the Resin One plug of each batch was placed in a separate bottle; in this way 24 separate reactions. Then 2ml of a 1M solution of AgN03 is added to each plug MeCN, and lml of a 1M solution of NEt3 in MeCN followed by lml of a 1M solution in MeCN of one of two olefins (acrylonitrile and methyl acrylate). The 24 bottles stop and shake for 24 hours. The plugs were then washed with MeCN (5x), DMF (3x), DCM (3x), MeOH (3x), and Et20 (3x) (v) Cleavage and Analysis 5 ml of 95% TFA was added to the stopper and the mixture was allowed to stir for 1 hour. The supernatants were separated and the resins were washed with MeOH (3x2ml). The combined supernatants were concentrated and the unpurified products were analyzed by HPLC and MS. The above reactions illustrate how the functionalized resins of the plugs are available by intervening in the synthesis of compounds, whereby the chemicals that are synthesized are covalently bound to a reactive group on the resin. In the synthesis complementation the synthesized compound can be cut from the resin. As an alternative to the use of the functionalized resins that act as solid supports for use in the preparation of the compounds in the manner described, the porous devices, for example the plugs 2, comprise a carrier that encapsulates an accidental material that can be prepared and / or used as follows: (a) The active material is prepared in the extract and the particular material of the solution. In this way, the porous device is designed to remove a predetermined material from a solution. (b) The active material can be covalently bound to a material which has an affinity for a material that is desired to be removed from a fluid. The porous device can then be in contact with, for example, being placed inside, the fluid, whereby the desired material is attracted to the material covalently bound to the active material by absorption / chemoabsorption. Suitably, the simple removal process involves an affinity between two materials and no current exchange of material between the porous device and the fluid. A sufficient amount of the material to be removed has been eliminated, the porous device can be removed from the fluid. Advantageously, the described process can obviate any need to the fluid filter, in a case where the material removed is the desired material and the remaining material is discarded. (c) The process of (b) can be adapted to remove metals or radioactive waste from fluids by the appropriate selection of the active material and / or functionalization thereof. (d) A ligand can be covalently bound to the active material of a porous device and this preparation can be used to trap cells or enzymes. (e) The active material can be a catalytic material or the active material can be functionalized by being bound to another compound or portion whereby it defines the catalytic material. (f) The active material can be a reagent for use in a reaction, for example a resin-based reagent, or the active material can be derivatized to provide such reagent. (g) A simple porous device can be incorporated once swept by a material and once swept by another material. For example, a scan can be prepared to remove the acid from a preparation to remove an amine. Such a device can be used to remove excess amine and acid from the reaction product of an acid and amine. (h) In a variation in (g), the two sweeps may be provided by different porous devices. Other porous devices are prepared to eliminate any other impurity can be used so that, after removing the devices, substantially without contaminating the rest of the amide product. (i) A range of porous devices can be prepared to define a mixing bed in a column, thereby allowing a range of different materials to be simultaneously removed from a fluid stream using the column. Advantageously, the use of the described porous devices allows the use of a range of active materials (or derivatized active materials) that otherwise must otherwise reagent together (or otherwise is incompatible and therefore need to be maintained separately). ). (j) A series of porous devices each incorporating ligands of different affinities that can be formed and used to determine the appropriate ligand to be used in an affinity column to remove a desired component from a mixture. (k) In view of the fact that the porous devices may include different reagents / materials which must in a usual manner be reactive to others but when the porous devices do not react with each other, even if two different porous devices are adjacent, a series of porous devices incorporating the appropriate reagents can be placed in a column and the synthesis of continuous flow affected by the passage of the appropriate materials through the column. (1) The active material or a derivative thereof can include a ligand prepared to allow a substance (eg, a drug) to be bound for time to time. The porous device can then be placed under the skin to allow for slow bleaching of the substance in the surrounding areas.

Claims

CLAIMS 1. A method of synthesis using a porous device comprising a body having an internal region which is porous, characterized in that an active material is trapped within the internal region. The method according to claim 1, characterized in that it includes the step of contacting the porous device with a first reagent under conditions that cause the first reagent to react with the active material, so that a bond is formed between the active material and the first reagent (or a fragment thereof). 3. The method according to claim 1 or claim 2, characterized in that they involve contacting the porous device with the reagents to prepare a compound that is covalently bound to the active material of the porous device. The method according to any of the preceding claims, characterized in that the active material is prepared to act as a support for a compound prepared in the solid phase synthesis. The method according to any of the preceding claims, characterized in that the active material includes a linker or is covalently linked to a linker in the synthesis. 6. The method according to any of the preceding claims, characterized in that it includes the step of unfolding a compound prepared from the active material. The method according to any of the preceding claims, characterized in that the materials that make the internal region are fixed in position in the internal region. The method according to any of the preceding claims, characterized in that the preparation and / or the position of particles of active material is predetermined. The method of compliance any of the preceding claims, characterized in that the internal region is not flowable. The method according to any of the preceding claims, characterized in that the internal region comprises a random network of pores whose network has a substantially fixed configuration. The method according to any of the preceding claims, characterized in that the porous device has a predetermined shape. The method according to any of the preceding claims, characterized in that the porosity on a surface of the device is substantially the same as the porosity of the internal region adjacent to the surface. The method according to any of the preceding claims, characterized in that the porous device is substantially self-supporting. The method according to any of the preceding claims, characterized in that the internal region of the porous device is defined by the active material so that the internal region consists essentially of active material. 15. The method according to any of claims 1 to 13, characterized in that the porous device comprises an inert material and an active material. 16. The method according to claim 15, characterized in that the inert material is prepared to trap the active material within the internal region of the device. The method according to claim 15 or claim 16, characterized in that the inert material defines a porous support medium and the active material is placed within the pores of porous support means. 18. The method according to any of claims 15 to 17, characterized in that the active material is not covalently bound to the porous support means. 19. The method according to any of claims 15 to 18, characterized in that the active material is in the form of a multiplicity of individual particles, wherein the particles are separated from one another by the inert material. 20. The method according to any of claims 15 to 19, characterized in that the inert material is a thermoplastic. 21. The method according to any of the preceding claims, characterized in that the particles of active material are substantially spherical. 22. A method of synthesizing a plurality of different compounds, the method uses a plurality of porous devices of the type described in any of claims 1 to 21, the method includes contacting a first porous device with a first sequence of reagents and contacting a second porous device with a second sequence of the reagents wherein the first and second sequences of the reagents are different, whereby the different compounds are prepared in the first and second porous devices. 23. The method according to claim 22, characterized in that it is a method of synthesizing the different compounds N wherein N is a positive integer, using the porous devices N, the method includes using different N sequences of the reagents and contacting the devices porous with a respective sequence so that they prepare respectively different compounds in the porous devices. 5 24. The method according to the claim 22 or claim 23, characterized in that the devices include identifying means for uniquely identifying the devices from one another. 25. A method of effecting an interaction between a 10 active material and another material (hereinafter an "interaction material"), the method uses a porous device comprising a body having an internal region that is porous, wherein the active material is trapped within the inner region . 26. A porous device comprising a body having an internal region that is porous, wherein an active material is trapped within the internal region. 27. The device according to claim 26, characterized in that the active material 20 includes a connector. 28. A device according to claim 26 or claim 27, characterized in that the device includes an identification means associated therewith. 25. 29. A placement or assembly comprising a A plurality of porous devices according to claim 26. 30. The placement or assembly according to claim 29, characterized in that each porous device includes a unique identification means. 31. The placement or assembly according to claim 29 or claim 30, characterized in that the device supports a plurality of different compounds. 32. The method of synthesizing a library of compounds, the method uses a plurality of porous devices in accordance with claim 26 and includes the step of subjecting each porous device to a unique sequence of treatments and / or reactions, thereby preparing different compounds in porous devices. 33. The method of manufacturing a porous device as described in any of the preceding claims, the method characterized in that it comprises causing a body having a porous internal region to form with an active material trapped therein. 34. The method according to claim 33, characterized in that it comprises sintering particles of an inert material with the particles of an active material by what defines the internal region of the porous device. 35. The method according to claim 33 or claim 34, characterized in that the active material is for use in a synthesis method according to any of claims 1 to 24; or is a reagent for use in a chemical reaction; or is a catalyst for use in a chemical reaction. 36. A substrate for use in solid phase chemistry, comprising a chemically active species that supports or contacts accessible functionality and a matrix forming material. 37. The use of a substrate according to claim 36, as a substrate in the solid phase chemistry.