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US 2006/0189764 A1Published application
Synthesis of functional polymers for use in organic synthesis and combinatorial chemistry
AssigneeMerck & Co., Inc.
InventorsCraig Lindsley, David Wisnoski
Life of this patent
Estimating the term…
Abstract
The present invention relates to a novel process for the preparation of solid-supported scavenging reagents and solid-supported functional polymers. The invention further relates to novel solid-supported functional polymers and to their use in organic synthesis and combinatorial chemistry.
Claims13
A process for the preparation of a compound of the formula I:
- wherein
- is an insoluble solid support selected from the group consisting of:
- poly(styrene-divinylbenzene), macroreticular poly(styrene-divinylbenzene), polystyrene which is radiation grafted to polypropylene, polystyrene which is radiation grafted to polyethylene, polystyrene which is radiation grafted to poly(tetrafluoroethylene), and polystyrene which is radiation grafted to poly(ethylene-tetrafluoroethylene) wherein the insoluble solid support is in a shape selected from a bead, a tube, a rod, a ring, a disk, or a well;
- L is —CH2—, —C(CH3)2—, —CH(CH3)—, —(CH2)nCH(CN)—, —(CH2)nCH(CO2Me)-, —(CH2)nCH(Ph)-, —(CH2)nC(CH3, Ph)-, —CH(CH2CH2Ph)-, or
- n is zero or an integer from 1 to 5;
- m is zero or an integer from 1 to 100;
- b is mMol content of initiator or solid-supported polymer per gram of insoluble solid support and is about 0.1 to about 5.0 in Mol per gram;
- R1 is selected from:
- wherein
- X is H, F, (CH2)nCl, (CH2)nBr, (CH2)nI, B(OH)2, (CH2)nCH═CH2, NCO, CH2NCO, CH(CH3)NCO, C(CH3)2NCO, CO2Me, CO2Et, CO2(t-Bu), CO2H, COCl, CO2CH(CF3)2, CO2Ph, CO2(pentafluorophenyl), CO2(pentachlorophenyl), CO2(N-succinimidyl), C(OMe)3, C(OEt)3, (CH2)nOH, (CH2)nCH(OH)CH20H, (CH2)nSH, CH2NHCH2CH2SH, (CH2)nNHC(═S)NH2, (CH2)nNH2, (CH2)nN(Me)2, (CH2)nN(Et)2, (CH2)n(iPr)2, CH(CH3)NH2, C(CH3)2NH2, CH2NHCH2CH2NH2, CH2NHCH2CH2NHCH2CH2NH2, CH2N(CH2CH2NH2)2, CH2NHCH2CH2N(CH2CH2NH2)2, CH2N(CH2CH20H)2, (CH2)n(morpholin-4-yl), (CH2)n(piperidin-1-yl), (CH2)n(4-methypiperazin-1-yl), N(SO2CF3)2, (CH2)nCHO, (CH2)nSi(Me)2H, (CH2)nSi(Et)2H, (CH2)Si(iPr)2H, (CH2)nSi(tBu)2H, (CH2)nSi(Ph)2H, (CH2)nSi(Ph)(tBu)H, (CH2)nSi(Me)2Cl, (CH2)nSi(Et)2Cl, (CH2)nSi(i-Pr)2Cl, (CH2)nSi(tBu)2Cl, (CH2)nSi(Ph)2Cl, (CH2)nSi(tBu)(Ph)Cl, P(Ph)2, P(o-tolyl)2,
- wherein n is zero or an integer from 1 to 5
- Y is H, Cl, Br, F, OH, or OMe;
- Z is NCO, CO2Me, CO2Et, CO2(i-Pr), CO2(n-Bu), CO2(t-Bu), CN, CO2H, COCl, CO2CH(CF3)2, C02(pentafluorophenyl), CO2(pentachlorophenyl), CO2Ph, CO2(N-succinimidyl), C(OMe)3, C(OEt)2, CON(OCH3)CH3, CHO, CH2OH, or C(CH3)2OH;
- and
- R4 is
- which comprises the step of microwave irradiating a mixture comprising a compound of the formula II
- and a compound III selected from:
14 more elements
A process for the preparation of a compound of the formula IV:
- wherein
- is an insoluble solid support selected from the group consisting of:
- poly(styrene-divinylbenzene), macroreticular poly(styrene-divinylbenzene), polystyrene which is radiation grafted to polypropylene, polystyrene which is radiation grafted to polyethylene, polystyrene which is radiation grafted to poly(tetrafluoroethylene), and polystyrene which is radiation grafted to poly (ethylene-tetrafluoroethylene) wherein the insoluble solid support is in a shape selected from a bead, a tube, a rod, a ring, a disk, or a well;
- L is —CH2—, —C(CH3)2—, —CH(CH3)—, —(CH2)nCH(CN)—, —(CH2)nCH(C02Me)-, —(CH2)nCH(Ph)-, —(CH2)nC(CH3, Ph)-, —CH(CH2CH2Ph)-, or
- n is zero or an integer from 1 to 5;
- m is zero or an integer from 1 to 100;
- w is an integer from 1 to 10;
- p is zero or an integer from 1 to 10;
- b is mMol content of initiator or solid-supported polymer per gram of insoluble solid support and is about 0.1 to about 5.0 mMol per gram;
- R1 and R2 are each independently the same or different and are selected from
- wherein
- X is H, F, (CH2)nCl, (CH2)nBr, (CH2)nI, B(OH)2, (CH2)nCH═CH2, NCO, CH2NCO, CH(CH3)NCO, C(CH3)2NCO, CO2Me, CO2Et, CO2(t-Bu), CO2H, COCl, CO2CH(CF3)2, CO2Ph, CO2(pentafluorophenyl), CO2(pentachlorophenyl), CO2(N-succinimidyl), C(OMe)3, C(OEt)3, (CH2)nOH, (CH2)nCH(OH)CH20H, (CH2)nSH, CH2NHCH2CH2SH, (CH2)nNHC(═S)NH2, (CH2)nNH2, (CH2)nN(Me)2, (CH2)nN(Et)2, (CH2)n(iPr)2, CH(CH3)NH2, C(CH3)2NH2, CH2NHCH2CH2NH2, CH2NHCH2CH2NHCH2CH2NH2, CH2N(CH2CH2NH2)2, CH2NHCH2CH2N(CH2CH2NH2)2, CH2N(CH2CH20H)2, (CH2)n(morpholin-4-yl), (CH2)n(piperidin-1-yl), (CH2)n(4-methypiperazin-1-yl), N(S02CF3)2, (CH2)nCHO, (CH2)nSi(Me)2H, (CH2)nSi(Et)2H, (CH2)Si(iPr)2H, (CH2)nSi(tBu)2H, (CH2)nSi(Ph)2H, (CH2)nSi(Ph)(tBu)H, (CH2)nSi(Me)2Cl, (CH2)nSi(Et)2Cl, (CH2)nSi(i-Pr)2Cl, (CH2)nSi(tBu)2Cl, (CH2)nSi(Ph)2Cl, (CH2)nSi(tBu)(Ph)Cl, P(Ph)2, P(o-tolyl)2,
- wherein n is zero or an integer from 1 to 5;
- Y is H, Cl, Br, F, OH, or OMe;
- Z is NCO, CO2Me, CO2Et, CO2(i-Pr), CO2(n-Bu), CO2(t-Bu), CN, CO2H, COCl, CO2CH(CF3)2, CO2(pentafluorophenyl), CO2(pentachlorophenyl), CO2Ph, CO2(N-succinimidyl), C(OMe)3, C(OEt)2, CON(OCH3)CH3, CHO, CH2OH, or C(CH3)2OH;
- and
- R4 is
- which comprises the step of microwave irradiating a mixture comprising a compound of the formula II
- a compound III selected from:
- and a compound V selected from:
17 more elements
A process for the preparation of a compound of the formula VI:
- wherein
- is an insoluble solid support selected from the group consisting of:
- poly(styrene-divinylbenzene), macroreticular poly(styrene-divinylbenzene), polystyrene which is radiation grafted to polypropylene, polystyrene which is radiation grafted to polyethylene, polystyrene which is radiation grafted to poly(tetrafluoroethylene), and polystyrene which is radiation grafted to poly(ethylene-tetrafluoroethylene) wherein the insoluble solid support is in a shape selected from a bead, a tube, a rod, a ring, a disk, or a well;
- L is —CH2—, —C(CH3)2—, —CH(CH3)—, —(CH2)nCH(CN)—, —(CH2)nCH(C02Me)-, —(CH2)nCH(Ph)-, —(CH2)nC(CH3, Ph)-, —CH(CH2CH2Ph)-, or
- n is zero or an integer from 1 to 5;
- m is zero or an integer from 1 to 100;
- w is an integer from 1 to 10;
- p is zero or an integer from 1 to 10;
- b is mMol content of initiator or solid-supported polymer per gram of insoluble solid support and is about 0.1 to about 5.0 mMol per gram;
- R1 is selected from
- R2 is selected from
- wherein
- X is H, F, (CH2)nCl, (CH2)nBr, (CH2)nI, B(OH)2, (CH2)nCH═CH2, NCO, CH2NCO, CH(CH3)NCO, C(CH3)2NCO, CO2Me, CO2Et, CO2(t-Bu), CO2H, COCl, CO2CH(CF3)2, CO2Ph, CO2(pentafluorophenyl), CO2(pentachlorophenyl), CO2(N-succinimidyl), C(OMe)3, C(OEt)3, (CH2)nOH, (CH2)nCH(OH)CH20H, (CH2)nSH, CH2NHCH2CH2SH, (CH2)nNHC(═S)NH2, (CH2)nNH2, (CH2)nN(Me)2, (CH2)nN(Et)2, (CH2)n(iPr)2, CH(CH3)NH2, C(CH3)2NH2, CH2NHCH2CH2NH2, CH2NHCH2CH2NHCH2CH2NH2, CH2N(CH2CH2NH2)2, CH2NHCH2CH2N(CH2CH2NH2)2, CH2N(CH2CH20H)2, (CH2)n(morpholin-4-yl), (CH2)n(piperidin-1-yl), (CH2)n(4-methypiperazin-1-yl), N(S02CF3)2, (CH2)nCHO, (CH2)nSi(Me)2H, (CH2)nSi(Et)2H, (CH2)Si(iPr)2H, (CH2)nSi(tBu)2H, (CH2)nSi(Ph)2H, (CH2)nSi(Ph)(tBu)H, (CH2)nSi(Me)2Cl, (CH2)nSi(Et)2Cl, (CH2)nSi(i-Pr) 2Cl, (CH2)nSi(tBu)2Cl, (CH2)nSi(Ph)2Cl, (CH2)nSi(tBu)(Ph)Cl, P(Ph)2, P(o-tolyl)2,
- wherein n is zero or an integer from 1 to 5;
- Y is H, Cl, Br, F, OH, or OMe;
- Z is NCO, CO2Me, CO2Et, CO2(i-Pr), CO2(n-Bu), CO2(t-Bu), CN, CO2H, COCl, CO2CH(CF3)2, CO2(pentafluorophenyl), CO2(pentachlorophenyl), CO2Ph, CO2(N-succinimidyl), C(OMe)3, C(OEt)2, CON(OCH3)CH3, CHO, CH2OH, or C(CH3)2OH;
- and
- R4 is
- which comprises the step of microwave irradiating a mixture comprising a compound of the formula II
- a compound VII selected from:
- and a compound VIII selected from:
- wherein the ratio of the compound VII and the compound VIII is about 2:1.
19 more elements
The compound according to claim 13 which is
- wherein
- is a polystyrene resin, m is from 1 to 100 and the bromine content is from about 4 to about 6 mmol/gram of resin.
The compound according to claim 13 which is
- wherein
- is a polystyrene resin, m is from 1 to 100 and the chlorine content is from about 5 to about 7 mmol/gram of resin.
The compound according to claim 13 which is
- wherein
- is a polystyrene, resin, m is from 1 to 100 and the pyridyl content is from about 5 to about 7 mmol/gram of resin.
The compound according to claim 13 which is
- wherein
- is a polystyrene resin, m is from 1 to 100, —NRaRb is selected from diethylamino, diisopropylamino, piperidinyl, morpholino and piperazinyl and the amine content is from about 4 to about 7 mmol/gram of resin.
The compound according to claim 13 which is
- wherein
- is a polystyrene resin, m is from 1 to 100, and the amine content is from about 3 to about 6 mmol/gram of resin.
The compound according to claim 13 which is
- wherein
- is a polystyrene resin, m is from 1 to 100, and the isocyanate content is from about 1 to about 4 mmol/gram of resin.
A compound which is:
- wherein
- is an insoluble solid support selected from the group consisting of:
- poly(styrene-divinylbenzene), macroreticular poly(styrene-divinylbenzene), polystyrene which is radiation grafted to polypropylene, polystyrene which is radiation grafted to polyethylene, polystyrene which is radiation grafted to poly(tetrafluoroethylene), and polystyrene which is radiation grafted to poly(ethylene-tetrafluoroethylene) wherein the insoluble solid support is in a shape selected from a bead, a tube, a rod, a ring, a disk, or a well;
- L is —CH2—, —C(CH3)2—, —CH(CH3)—, —(CH2)nCH(CN)—, —(CH2)nCH(CO2Me)-, —(CH2)nCH(Ph)-, —(CH2)nC(CH3, Ph)-, —CH(CH2CH2Ph)-, or
- n is zero or an integer from 1 to 5;
- m is zero or an integer from 1 to 100;
- b is mMol content of initiator or solid-supported polymer per gram of insoluble solid support and is about 0.1 to about 5.0 mMol per gram;
- R1 is selected from:
- wherein
- X is H, F, (CH2)nCl, (CH2)nBr, (CH2)nI, B(OH)2, (CH2)nCH═CH2, NCO, CH2NC0, CH(CH3)NCO, C(CH3)2NCO, CO2Me, CO2Et, CO2(t-Bu), CO2H, COCl, CO2CH(CF3)2, CO2Ph, CO2(pentafluorophenyl), CO2(pentachlorophenyl), CO2(N-succinimidyl), C(OMe)3, C(OEt)3, (CH2)nOH, (CH2)nCH(OH)CH20H, (CH2)nSH, CH2NHCH2CH2SH, (CH2)nNHC(═S)NH2, (CH2)nNH2, (CH2)nN(Me)2, (CH2)nN(Et)2, (CH2)n(iPr)2, CH(CH3)NH2, C(CH3)2NH2, CH2NHCH2CH2NH2, CH2NHCH2CH2NHCH2CH2NH2, CH2N(CH2CH2NH2)2, CH2NHCH2CH2N(CH2CH2NH2)2, CH2N(CH2CH20H)2, (CH2)n(morpholin-4-yl), (CH2)n(piperidin-1-yl), (CH2)n(4-methypiperazin-1-yl), N(S02CF3)2, (CH2)nCHO, (CH2)nSi(Me)2H, (CH2)nSi(Et)2H, (CH2)Si(iPr)2H, (CH2)nSi(tBu)2H, (CH2)nSi(Ph)2H, (CH2)nSi(Ph)(tBu)H, (CH2)nSi(Me)2Cl, (CH2)nSi(Et)2Cl, (CH2)nSi(i-Pr)2Cl, (CH2)nSi(tBu)2Cl, (CH2)nSi(Ph)2Cl, (CH2)nSi(tBu)(Ph)Cl, P(Ph) 2, P(o-tolyl)2,
- wherein n is zero or an integer from 1 to 5;
- Y is H, Cl, Br, F, OH, or OMe;
- Z is NCO, CO2Me, CO2Et, CO2(i-Pr), CO2(n-Bu), CO2(t-Bu), CN, CO2H, COCl, CO2CH(CF3)2, CO2(pentafluorophenyl), CO2(pentachlorophenyl), CO2Ph, CO2(N-succinimidyl), C(OMe)3, C(OEt)2, CON(OCH3)CH3, CHO, CH2OH, or C(CH3)2OH;
- and
- R4 is
12 more elements
Dependencies are inferred from the claim text.