Patent EA-004061-B1 (EA)
Title: Fluorophenyl resin compounds
Inventor: SALVINO JOSEPH M
IPC: C08F8/18
Filed: 1999-06-23
Abstract: 1. A fluorophenyl resin compound of formula wherein is a solid support; A is selected from -L-SO2-, -L-NR3SO2-, L is a chemical bond, m is 1 to 5; P is 0, 1 or 2; B is F, OW or SO2Z; D is CH or N; W is hydrogen, tripyrrolidinophosphonium, C(O)V, C(O)Ra, C(O)NRbRc, C(O)ORa, SO2Ra or V is Cl or imidazol-1-yl; Y is O or NR3; Z is Cl, -OH, OR2 or NRaRi; Ra and Rf are independently aliphatic radicals selected from the group including straight or branched alkyl having about 1-20 carbon atoms, straight or branched alkenyl of about 2-15 carbon atoms, straight or branched alkynyl of 2 to about 15 carbon atoms, cycloalkyl having about 3 to about 10 carbon atoms, cycloalkenyl having of about 3 to about 10 carbon atoms, optionally substituted with one or more substituents which may be the same or different, heterocyclyl having of about 3 to about 10 ring atoms, in which one or more of the atoms in the ring system is/are element(s) other than carbon, for example nitrogen, oxygen or sulfur, wherein heterocyclyl is optionally substituted by one or more substituents which may be the same or different, and are as defined above, heterocyclenyl having about 3 to about 10 ring atoms, in which one or more of the atoms in the ring system is/are element(s) other than carbon, for example nitrogen, oxygen or sulfur atoms, wherein heterocyclenyl may be optionally substituted by one or more ring system substituents which are as defined above, aralkenyl having from 6 to about 14 carbon atoms, aralkyloxyalkyl, aralkyloxycarbonylalkyl, aralkyl, aralkynyl, araloxyalkenyl, heteroaryl-alkenylenyl-group, wherein heteroaryl is an aromatic monocyclic or multicyclic ring system of about 5 to about 14 ring atoms, and alkenylenyl is a divalent group derived from a straight or branched chain hydrocarbon containing at least one carbon-carbon double bond, heteroaryl-alkylenyl-group wherein heteroaryl is as defined above and alkylenyl is a straight or branched bivalent hydrocarbon chain of 1 to about 20 carbon atoms, heteroaralkyloxyalkenyl means heteroaralkyl-O-alkenylenyl-group wherein heteroaralkyl and alkenylenyl are defined above, heteroaralkyloxyalkyl means a heteroaralkyl-O-alkylene-group wherein heteroaralkyl and alkylene are defined above, heteroarylcycloalkenyl with about 5 to about 6 ring atoms, fused arylheterocyclyl means a radical derived from a fused aryl and heterocyclyl as defined above by removal of a hydrogen atom from heterocyclyl portion, fused heteroarylheterocyclyl is a radical derived from a fused heteroaryl and heterocyclyl as defined above by removal of a hydrogen atom from the heterocyclyl portion, fused arylheterocyclenyl is a radical derived from a fused aryl and heterocyclenyl as defined above by removal of a hydrogen atom from the heterocyclenyl portion, fused heteroarylheterocyclenyl is a radical derived from a fused heteroaryl and heterocyclenyl as defined above by the removal of a hydrogen atom from heterocyclenyl portion, or aromatic radicals selected from the group including aryl having from 6 to about 14 carbon atoms, fused cycloalkenylaryl is a radical derived from a fused arylcycloalkenyl as defined above by removal of hydrogen atom from the aryl portion, fused cycloalkylaryl is a radical derived from a fused arylcycloalkyl as defined above by removal of a hydrogen atom from the aryl portion, fused heterocyclylaryl which is a radical derived from a fused arylheterocyclyl as defined above by removal of a hydrogen atom from the heterocyclyl portion, fused heterocyclenylaryl which is a radical derived from a fused arylheterocyclenyl as defined above by removal of a hydrogen atom from the aryl portion, heteroaryl having from about 5 to about 14 ring atoms, in which one or more of the atoms in the ring is/are other than carbon, such as nitrogen, oxygen or sulfur, fused cycloalkylheteroaryl which is a radical derived from a fused heteroarylcycloalkyl as defined above by removal of a hydrogen atom from the heteroaryl portion, fused cycloalkenylheteroaryl which is a radical derived from a fused heteroarylcycloalkenyl as defined above by removal of a hydrogen atom from heteroaryl portion, fused heterocyclenylheteroaryl which is a radical derived from a fused heteroarylheterocyclenyl as defined above by the removal of a hydrogen atom from the heteroaryl portion, fused heterocyclylheteroaryl which is a radical derived from a fused heteroarylheterocyclyl as defined above by removal of a hydrogen atom from the heteroaryl portion, Rb and Rc are independently H, aliphatic or aromatic as defined above, or Rb and Rc, taken together with the N atom through which they are attached, form an azaheterocyclyl or azaheterocyclenyl; Ri is CH2Rf; Ro, R1 and R2 are a ring system substituents, attached to aromatic or non-aromatic ring systems inclusive of hydrogen, alkyl, aralkyl, heteroaryl, aryl, heteroaralkyl, hydroxy, hydroxyalkyl, alkoxy, aryloxy, aralkoxy, acyl, aroyl, halo, nitro, cyano, formyl, carboxy, alkoxycarbonyl, aryloxycarbonyl, aralkoxycarbonyl, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, alkylsulfinyl, arylsulfinyl, nilrile, NO2 heteroarylsulfinyl, alkylthio, arylthio, heteroarylthio, aralkylthio, heteroaralkyllhio, cycloalkyl, cycloalkenyl, heterocyclyl, heterocyclenyl, aryldiazo, hcteroaryldiazo, amidino, amino, aminoalkyl, carbamyl and sulfamyl. When a ring system is saturated or partially saturated, the "ring system substituent" further comprises methylene (H2C=), oxo (O=) and thioxo (S=), or Ro and R1 taken together with the adjacent carbon atoms through which they are linked form a 6 membered aryl or 5 to 6 membered heteroaryl, in which one or more of the atoms in the ring system is/are other than carbon, for example, nitrogen, oxygen or sulfur; R3 is H or lower alkyl with about 1-2 C with straight or branched chain; R4 R5 R6 and R7 are independently ring system substituents as defined above; or R4 and R5 taken together with the carbon atoms through which they are linked form a 6 membered aryl or 5 to 6 membered heteroaryl as defined above; and R11 R12re independently about 1-20 C alkyl with straight or branched chain, heteroaryl as stated above, or about 6-14 C aryl. 2. The fluorophenyl resin compound of claim 1 wherein R0, R1 and R2 are F, and R3, R4, R5, R6 and R7 are H. 3. The fluorophenyl resin compound of claim 2 wherein A is A is selected from L is a chemical bond, m is l; or NR3SO2, wherein Y is O or NR3. 4. The fluorophenyl resin compound of claim 3 wherein Y is NR3 and R3 is H. 5. The fluorophenyl resin compound of claim 4 wherein B is -OH. 6. The fluorophenyl resin compound of claim 4 wherein B is -SO3H or -SO2Cl. 7. A fluorophenyl resin compound according to claim 1 selected from 4-hydroxy-2,3,5,6-tetrafluorobenzamidomethyl-polystyreneresin, 2,3,5,6-tetrafluorobenzamidomethyl-4-sulfonic acid-polystyrene resin, 2,3,5,6-tetrafluorobenzamidomethyl-4-sulfonyl chloride-polystyrene resin, 4-hydroxy-2,3,5,6-tetrafluorobenzoyloxymethyl-polystyrene resin, 2,3,5,6-tetrafluorobenzoyloxymethyl-4-sulfonic acid-polystyrene resin, 2,3,5,6-tetrafluorobenzoyloxymethyl-4-sulfonyl chloride-polystyrene resin, 4-hydroxy-2,3,5,6-pentafluorobenzoyl-polystyrene resin, 2,3,5,6-tetrafluorobenzoyl-4-sulfonic acid-polystyrene resin, 2,3,5,6-tetrafluorobenzoyl-4-sulfonyl chloride-polystyrene resin, 4-hydroxy-2,3,5,6-tetrafluorophenylsulfonamidomethyl-polystyrene resin, 2,3,5,6-tetrafluorophenylsulfonamidomethyl-4-sulfonic acid-polystyrene resin, 2,3,5,6-tetrafluorophenylsulfonamidomethyl-4-sulfonyl chloride-polystyrene resin, N-(4-hydroxy-2,3,5,6-tetrafluorobenzoyl)-piperidinomethyl-polystyrene resin, N-(2,3,5,6-tetrafluorobenzoyl-4-sulfonic acid)-piperidinomethyl-polystyrene resin, N-(2,3,5,6-tetrafluorobenzoyl-4-sulfonylchloride)-piperidinomethyl-4-polystyrene resin, N-(4-hydroxy-2,3,5,6-tetrafluorophenylsulfonyl)-piperidinomethyl-polystyrene resin, N-((2,3,5,6-tetrafluorophenyl-4-sulfonicacid)sulfonyl)-piperidinomethyl-polystyrene resin, N-((2,3,5,6-tetrafluorophenyl-4-sulfonylchloride)sulfonyl)-piperidinomethyl-polystyrene resin, 4-hydroxy-2,3,5,6-tetrafluorophenyl-polystyrene resin, 2,3,5,6-tetrafluorophenyl-4-sulfonic acid-polystyrene resin, 2,3,5,6-tetrafluorophenyl-4-sulfonyl chloride polystyrene resin, 4-hydroxy-2,3,5,6-tetrafluorophenylsulfonyl-polystyrene resin, 4-(tripyrolidinium-O-phosphonium)-2,3,5,6-tetrafluorotetrafluorobenzamidomethyl-copoly(styrene-1 %-divinylbenzene)-resin, 4-(N,N'-didisopropyl-isourea)-2,3,5,6-tetrafluorotetrafluorobenzamidomethyl-copoly(styrene-1%-divinylbenzene)-resin, 2,3,5,6-tetrafluorophenylsulfonyl-4-sulfonic acid-polystyrene resin, and 2,3,5,6-tetrafluorophenylsulfonyl-4-sulfonyl chloride-polystyrene resin. 8. A fluorophenyl resin compound according to claim 1 selected from 4-hydroxy-2,3,5,6-tetrafluorobenzamidomethyl-polystyrene resin, 2,3,5,6-tetrafluorobenzamidomethyl-4-sulfonic acid-polystyrene resin, designated herein as 2,3,5,6-tetrafluorobenzamidomethyl-4-sulfonyl chloride-polystyrene resin, 4-hydroxy-2,3,5,6-pentafluorobenzoyl-polystyrene resin, 2,3,5,6-tetrafluorobenzoyl-4-sulfonic acid-polystyrene resin, 2,3,5,6-tetrafluorobenzoyl-4-sulfonyl chloride-polystyrene resin, 4-hydroxy-2,3,5,6-tetrafluorophenylsulfonamidomethyl-polystyrene resin, 4-(tripyrolidinium-O-phosphonium)-2,3,5,6-tetrafluorotetrafluorobenzamidomethyl-copoly(styrene-1 %-divinylbenzene)-resin, 4-(N,N'-didisopropyl-isourea)-2,3,5,6-tetrafluorotetrafluorobenzamidomethyl-copoly(styrene-1%-divinylbenzene)-resin, 2,3,5,6-tetrafluorophenylsulfonamidomethyl-4-sulfonic acid-polystyrene resin and 2,3,5,6-tetrafluorophenylsulfonamidomethyl-4-sulfonyl chloride-polystyrene resin. 9. The fluorophenyl resin compound of claim 4 wherein B is OC(O)Ra. 10. A process for preparing an amide of formula wherein Ra is independently aliphatic radical selected from the group including straight or branched alkyl having about 1-20 carbon atoms, straight or branched alkenyl of about 2-15 carbon atoms, straight or branched alkynyl of 2 to