OA11773A - Process for the solid phase synthesis of aldehyde,ketone, oxime, amine, hydroxamic acid and alpha, b eta-unsaturated carboxylic acid and aldehyde compounds. - Google Patents
Process for the solid phase synthesis of aldehyde,ketone, oxime, amine, hydroxamic acid and alpha, b eta-unsaturated carboxylic acid and aldehyde compounds. Download PDFInfo
- Publication number
- OA11773A OA11773A OA1200000355A OA1200000355A OA11773A OA 11773 A OA11773 A OA 11773A OA 1200000355 A OA1200000355 A OA 1200000355A OA 1200000355 A OA1200000355 A OA 1200000355A OA 11773 A OA11773 A OA 11773A
- Authority
- OA
- OAPI
- Prior art keywords
- formula
- alkyl
- resin
- independently
- halogen
- Prior art date
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- -1 aldehyde compounds Chemical class 0.000 title claims description 248
- 238000000034 method Methods 0.000 title claims description 142
- 230000008569 process Effects 0.000 title claims description 116
- 239000002253 acid Substances 0.000 title claims description 95
- NEAQRZUHTPSBBM-UHFFFAOYSA-N 2-hydroxy-3,3-dimethyl-7-nitro-4h-isoquinolin-1-one Chemical compound C1=C([N+]([O-])=O)C=C2C(=O)N(O)C(C)(C)CC2=C1 NEAQRZUHTPSBBM-UHFFFAOYSA-N 0.000 title claims description 64
- 150000002576 ketones Chemical class 0.000 title description 20
- 150000001732 carboxylic acid derivatives Chemical class 0.000 title description 15
- 150000001412 amines Chemical class 0.000 title description 13
- 150000002923 oximes Chemical class 0.000 title description 5
- 238000010532 solid phase synthesis reaction Methods 0.000 title description 4
- 150000001299 aldehydes Chemical class 0.000 title description 2
- 239000011347 resin Substances 0.000 claims abstract description 484
- 229920005989 resin Polymers 0.000 claims abstract description 484
- 150000001875 compounds Chemical class 0.000 claims abstract description 146
- 238000004519 manufacturing process Methods 0.000 claims abstract description 7
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 254
- MYRTYDVEIRVNKP-UHFFFAOYSA-N 1,2-Divinylbenzene Chemical compound C=CC1=CC=CC=C1C=C MYRTYDVEIRVNKP-UHFFFAOYSA-N 0.000 claims description 243
- 125000000217 alkyl group Chemical group 0.000 claims description 161
- 239000000203 mixture Substances 0.000 claims description 107
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 85
- 125000003118 aryl group Chemical group 0.000 claims description 82
- 229910052736 halogen Inorganic materials 0.000 claims description 73
- 125000003545 alkoxy group Chemical group 0.000 claims description 71
- 125000005647 linker group Chemical group 0.000 claims description 67
- 150000002367 halogens Chemical class 0.000 claims description 56
- 238000006243 chemical reaction Methods 0.000 claims description 55
- 150000002825 nitriles Chemical class 0.000 claims description 51
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims description 49
- 125000001931 aliphatic group Chemical group 0.000 claims description 49
- 125000001072 heteroaryl group Chemical group 0.000 claims description 48
- 229910052739 hydrogen Inorganic materials 0.000 claims description 43
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 43
- 229910052757 nitrogen Inorganic materials 0.000 claims description 42
- 125000004432 carbon atom Chemical group C* 0.000 claims description 37
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 35
- 239000007787 solid Substances 0.000 claims description 35
- 239000003153 chemical reaction reagent Substances 0.000 claims description 33
- 125000002947 alkylene group Chemical group 0.000 claims description 32
- 229910052799 carbon Inorganic materials 0.000 claims description 31
- 239000002904 solvent Substances 0.000 claims description 31
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 30
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 29
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 27
- 125000000623 heterocyclic group Chemical group 0.000 claims description 26
- 239000001257 hydrogen Substances 0.000 claims description 25
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 23
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 23
- 229910052760 oxygen Inorganic materials 0.000 claims description 22
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 21
- 229910052717 sulfur Inorganic materials 0.000 claims description 21
- 125000004429 atom Chemical group 0.000 claims description 20
- 125000006242 amine protecting group Chemical group 0.000 claims description 19
- 229910052731 fluorine Inorganic materials 0.000 claims description 18
- 238000005859 coupling reaction Methods 0.000 claims description 17
- 239000001301 oxygen Substances 0.000 claims description 16
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 15
- 125000001424 substituent group Chemical group 0.000 claims description 15
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 14
- 230000008878 coupling Effects 0.000 claims description 13
- 238000010168 coupling process Methods 0.000 claims description 13
- 125000004475 heteroaralkyl group Chemical group 0.000 claims description 13
- 150000004678 hydrides Chemical group 0.000 claims description 13
- 125000000304 alkynyl group Chemical group 0.000 claims description 12
- 125000001153 fluoro group Chemical group F* 0.000 claims description 12
- 150000002443 hydroxylamines Chemical class 0.000 claims description 12
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 11
- 125000004450 alkenylene group Chemical group 0.000 claims description 11
- 125000004419 alkynylene group Chemical group 0.000 claims description 11
- 239000003638 chemical reducing agent Substances 0.000 claims description 11
- 125000004350 aryl cycloalkyl group Chemical group 0.000 claims description 10
- 150000001721 carbon Chemical group 0.000 claims description 10
- 125000002524 organometallic group Chemical group 0.000 claims description 10
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical group N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 claims description 9
- 229910010084 LiAlH4 Inorganic materials 0.000 claims description 9
- 125000005349 heteroarylcycloalkyl group Chemical group 0.000 claims description 9
- 239000012280 lithium aluminium hydride Substances 0.000 claims description 9
- RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 claims description 9
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 8
- 239000003999 initiator Substances 0.000 claims description 8
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 8
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
- 239000011260 aqueous acid Substances 0.000 claims description 7
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 7
- 238000006894 reductive elimination reaction Methods 0.000 claims description 7
- 239000011593 sulfur Substances 0.000 claims description 7
- 239000002168 alkylating agent Substances 0.000 claims description 6
- 229940100198 alkylating agent Drugs 0.000 claims description 6
- 150000001768 cations Chemical class 0.000 claims description 6
- 239000003795 chemical substances by application Substances 0.000 claims description 6
- 125000004367 cycloalkylaryl group Chemical group 0.000 claims description 6
- SQDFHQJTAWCFIB-UHFFFAOYSA-N n-methylidenehydroxylamine Chemical compound ON=C SQDFHQJTAWCFIB-UHFFFAOYSA-N 0.000 claims description 6
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 5
- 125000005215 cycloalkylheteroaryl group Chemical group 0.000 claims description 5
- 150000002148 esters Chemical class 0.000 claims description 5
- 150000007934 α,β-unsaturated carboxylic acids Chemical class 0.000 claims description 5
- 125000002993 cycloalkylene group Chemical group 0.000 claims description 4
- 125000005842 heteroatom Chemical group 0.000 claims description 4
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 4
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 4
- UWTDFICHZKXYAC-UHFFFAOYSA-N boron;oxolane Chemical group [B].C1CCOC1 UWTDFICHZKXYAC-UHFFFAOYSA-N 0.000 claims description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 3
- DBGVGMSCBYYSLD-UHFFFAOYSA-N tributylstannane Chemical group CCCC[SnH](CCCC)CCCC DBGVGMSCBYYSLD-UHFFFAOYSA-N 0.000 claims description 3
- 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 claims description 2
- 101150020251 NR13 gene Proteins 0.000 claims description 2
- 150000001335 aliphatic alkanes Chemical class 0.000 claims description 2
- 150000001728 carbonyl compounds Chemical class 0.000 claims description 2
- CJGBPPZRFOVLNI-UHFFFAOYSA-N cyclohexane;oxolane Chemical compound C1CCOC1.C1CCCCC1 CJGBPPZRFOVLNI-UHFFFAOYSA-N 0.000 claims description 2
- 229940002612 prodrug Drugs 0.000 claims description 2
- 239000000651 prodrug Substances 0.000 claims description 2
- 229910052703 rhodium Inorganic materials 0.000 claims description 2
- SGPGESCZOCHFCL-UHFFFAOYSA-N Tilisolol hydrochloride Chemical compound [Cl-].C1=CC=C2C(=O)N(C)C=C(OCC(O)C[NH2+]C(C)(C)C)C2=C1 SGPGESCZOCHFCL-UHFFFAOYSA-N 0.000 claims 5
- 229910052794 bromium Inorganic materials 0.000 claims 2
- 229910052801 chlorine Inorganic materials 0.000 claims 2
- 125000005055 alkyl alkoxy group Chemical group 0.000 claims 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 232
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 217
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Substances OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 65
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 64
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 63
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 48
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical class CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 43
- 239000000243 solution Substances 0.000 description 43
- 235000001014 amino acid Nutrition 0.000 description 34
- 229940024606 amino acid Drugs 0.000 description 34
- 238000005481 NMR spectroscopy Methods 0.000 description 33
- 150000001413 amino acids Chemical class 0.000 description 31
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 27
- 125000006413 ring segment Chemical group 0.000 description 26
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 22
- 150000003254 radicals Chemical class 0.000 description 22
- 238000003786 synthesis reaction Methods 0.000 description 22
- 230000015572 biosynthetic process Effects 0.000 description 21
- 125000006239 protecting group Chemical group 0.000 description 20
- 239000011541 reaction mixture Substances 0.000 description 19
- 239000000725 suspension Substances 0.000 description 19
- 101150041968 CDC13 gene Proteins 0.000 description 18
- 238000011068 loading method Methods 0.000 description 18
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 17
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 16
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- 150000001204 N-oxides Chemical class 0.000 description 12
- 238000000921 elemental analysis Methods 0.000 description 12
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 12
- JWVTWJNGILGLAT-UHFFFAOYSA-N 1-ethenyl-4-fluorobenzene Chemical compound FC1=CC=C(C=C)C=C1 JWVTWJNGILGLAT-UHFFFAOYSA-N 0.000 description 11
- 125000000524 functional group Chemical group 0.000 description 11
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 11
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 10
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
- 125000004122 cyclic group Chemical group 0.000 description 10
- 241000534944 Thia Species 0.000 description 9
- 125000003342 alkenyl group Chemical group 0.000 description 9
- ZXKINMCYCKHYFR-UHFFFAOYSA-N aminooxidanide Chemical compound [O-]N ZXKINMCYCKHYFR-UHFFFAOYSA-N 0.000 description 9
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 9
- 229940126214 compound 3 Drugs 0.000 description 9
- 102000004196 processed proteins & peptides Human genes 0.000 description 9
- 125000004434 sulfur atom Chemical group 0.000 description 9
- SCZNXLWKYFICFV-UHFFFAOYSA-N 1,2,3,4,5,7,8,9-octahydropyrido[1,2-b]diazepine Chemical compound C1CCCNN2CCCC=C21 SCZNXLWKYFICFV-UHFFFAOYSA-N 0.000 description 8
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 8
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 8
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 8
- 238000005903 acid hydrolysis reaction Methods 0.000 description 8
- 125000002252 acyl group Chemical group 0.000 description 8
- 239000002798 polar solvent Substances 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 239000007790 solid phase Substances 0.000 description 8
- JBLIDPPHFGWTKU-UHFFFAOYSA-N 2,6-dichlorobenzoyl chloride Chemical compound ClC(=O)C1=C(Cl)C=CC=C1Cl JBLIDPPHFGWTKU-UHFFFAOYSA-N 0.000 description 7
- BQXUPNKLZNSUMC-YUQWMIPFSA-N CCN(CCCCCOCC(=O)N[C@H](C(=O)N1C[C@H](O)C[C@H]1C(=O)N[C@@H](C)c1ccc(cc1)-c1scnc1C)C(C)(C)C)CCOc1ccc(cc1)C(=O)c1c(sc2cc(O)ccc12)-c1ccc(O)cc1 Chemical compound CCN(CCCCCOCC(=O)N[C@H](C(=O)N1C[C@H](O)C[C@H]1C(=O)N[C@@H](C)c1ccc(cc1)-c1scnc1C)C(C)(C)C)CCOc1ccc(cc1)C(=O)c1c(sc2cc(O)ccc12)-c1ccc(O)cc1 BQXUPNKLZNSUMC-YUQWMIPFSA-N 0.000 description 7
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 7
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 7
- 150000001408 amides Chemical class 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 7
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 7
- 238000010647 peptide synthesis reaction Methods 0.000 description 7
- 229910052938 sodium sulfate Inorganic materials 0.000 description 7
- 235000011152 sodium sulphate Nutrition 0.000 description 7
- CFMZSMGAMPBRBE-UHFFFAOYSA-N 2-hydroxyisoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(O)C(=O)C2=C1 CFMZSMGAMPBRBE-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 6
- 230000008901 benefit Effects 0.000 description 6
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 6
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 6
- 238000001035 drying Methods 0.000 description 6
- 239000003960 organic solvent Substances 0.000 description 6
- 239000000741 silica gel Substances 0.000 description 6
- 229910002027 silica gel Inorganic materials 0.000 description 6
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
- 239000003875 Wang resin Substances 0.000 description 5
- NERFNHBZJXXFGY-UHFFFAOYSA-N [4-[(4-methylphenyl)methoxy]phenyl]methanol Chemical compound C1=CC(C)=CC=C1COC1=CC=C(CO)C=C1 NERFNHBZJXXFGY-UHFFFAOYSA-N 0.000 description 5
- 150000001450 anions Chemical class 0.000 description 5
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 5
- 150000004795 grignard reagents Chemical class 0.000 description 5
- RCCPEORTSYDPMB-UHFFFAOYSA-N hydroxy benzenecarboximidothioate Chemical compound OSC(=N)C1=CC=CC=C1 RCCPEORTSYDPMB-UHFFFAOYSA-N 0.000 description 5
- MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 5
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 5
- 125000005544 phthalimido group Chemical group 0.000 description 5
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 4
- GNPISAHACGIXLZ-UHFFFAOYSA-N 3-(4-methylphenoxy)propanoic acid Chemical compound CC1=CC=C(OCCC(O)=O)C=C1 GNPISAHACGIXLZ-UHFFFAOYSA-N 0.000 description 4
- QDSFNOHWQKVVEB-UHFFFAOYSA-N 4-(diethoxyphosphorylmethyl)morpholine Chemical compound CCOP(=O)(OCC)CN1CCOCC1 QDSFNOHWQKVVEB-UHFFFAOYSA-N 0.000 description 4
- 102000052567 Anaphase-Promoting Complex-Cyclosome Apc1 Subunit Human genes 0.000 description 4
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
- 239000012448 Lithium borohydride Substances 0.000 description 4
- 229920001367 Merrifield resin Polymers 0.000 description 4
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
- 108091006463 SLC25A24 Proteins 0.000 description 4
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 4
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 4
- 125000003435 aroyl group Chemical group 0.000 description 4
- 238000003776 cleavage reaction Methods 0.000 description 4
- 238000009833 condensation Methods 0.000 description 4
- 230000005494 condensation Effects 0.000 description 4
- 238000009510 drug design Methods 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 125000005843 halogen group Chemical group 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- 125000002249 indol-2-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([*])=C([H])C2=C1[H] 0.000 description 4
- 238000002329 infrared spectrum Methods 0.000 description 4
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 4
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 4
- 230000000269 nucleophilic effect Effects 0.000 description 4
- 125000004043 oxo group Chemical group O=* 0.000 description 4
- 239000002245 particle Substances 0.000 description 4
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 description 4
- 229910052698 phosphorus Inorganic materials 0.000 description 4
- 229920000642 polymer Polymers 0.000 description 4
- 238000007154 radical cyclization reaction Methods 0.000 description 4
- 230000007017 scission Effects 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- 150000003573 thiols Chemical class 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- ZCZIRBNZMFUCOH-UHFFFAOYSA-N 1-(2-fluoro-4-hydroxyphenyl)ethanone Chemical compound CC(=O)C1=CC=C(O)C=C1F ZCZIRBNZMFUCOH-UHFFFAOYSA-N 0.000 description 3
- KQZLRWGGWXJPOS-NLFPWZOASA-N 1-[(1R)-1-(2,4-dichlorophenyl)ethyl]-6-[(4S,5R)-4-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]-5-methylcyclohexen-1-yl]pyrazolo[3,4-b]pyrazine-3-carbonitrile Chemical compound ClC1=C(C=CC(=C1)Cl)[C@@H](C)N1N=C(C=2C1=NC(=CN=2)C1=CC[C@@H]([C@@H](C1)C)N1[C@@H](CCC1)CO)C#N KQZLRWGGWXJPOS-NLFPWZOASA-N 0.000 description 3
- TVTJUIAKQFIXCE-HUKYDQBMSA-N 2-amino-9-[(2R,3S,4S,5R)-4-fluoro-3-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-7-prop-2-ynyl-1H-purine-6,8-dione Chemical compound NC=1NC(C=2N(C(N(C=2N=1)[C@@H]1O[C@@H]([C@H]([C@H]1O)F)CO)=O)CC#C)=O TVTJUIAKQFIXCE-HUKYDQBMSA-N 0.000 description 3
- HBAHZZVIEFRTEY-UHFFFAOYSA-N 2-heptylcyclohex-2-en-1-one Chemical compound CCCCCCCC1=CCCCC1=O HBAHZZVIEFRTEY-UHFFFAOYSA-N 0.000 description 3
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Classifications
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- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/26—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D307/30—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D307/32—Oxygen atoms
- C07D307/33—Oxygen atoms in position 2, the oxygen atom being in its keto or unsubstituted enol form
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- C07C259/06—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids having carbon atoms of hydroxamic groups bound to hydrogen atoms or to acyclic carbon atoms
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- C07C259/08—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids having carbon atoms of hydroxamic groups bound to carbon atoms of rings other than six-membered aromatic rings
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- C07C259/10—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids having carbon atoms of hydroxamic groups bound to carbon atoms of six-membered aromatic rings
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- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/58—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4
- C07D311/68—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4 with nitrogen atoms directly attached in position 4
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- C07D311/78—Ring systems having three or more relevant rings
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- C08J7/00—Chemical treatment or coating of shaped articles made of macromolecular substances
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- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
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- General Physics & Mathematics (AREA)
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- Biochemistry (AREA)
- Analytical Chemistry (AREA)
- High Energy & Nuclear Physics (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Addition Polymer Or Copolymer, Post-Treatments, Or Chemical Modifications (AREA)
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Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US09/103,872 US6133409A (en) | 1996-12-19 | 1998-06-24 | Process for the solid phase synthesis of aldehyde, ketone, oxime, amine, hydroxamic acid and αβ-unsaturated carboxylic acid and aldehyde compounds |
Publications (1)
| Publication Number | Publication Date |
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| OA11773A true OA11773A (en) | 2005-07-25 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
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| OA1200000355A OA11773A (en) | 1998-06-24 | 1999-06-23 | Process for the solid phase synthesis of aldehyde,ketone, oxime, amine, hydroxamic acid and alpha, b eta-unsaturated carboxylic acid and aldehyde compounds. |
Country Status (18)
| Country | Link |
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| US (1) | US6133409A (pl) |
| EP (3) | EP1359136A3 (pl) |
| JP (1) | JP4070407B2 (pl) |
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| CN (3) | CN1307553A (pl) |
| AP (1) | AP2000001994A0 (pl) |
| BG (1) | BG65311B1 (pl) |
| BR (1) | BR9911499A (pl) |
| CA (1) | CA2335511A1 (pl) |
| EA (1) | EA004741B1 (pl) |
| HU (1) | HUP0102856A3 (pl) |
| IL (2) | IL139796A0 (pl) |
| NO (1) | NO20006566L (pl) |
| OA (1) | OA11773A (pl) |
| PL (1) | PL199122B1 (pl) |
| SK (1) | SK20142000A3 (pl) |
| UA (1) | UA71917C2 (pl) |
| WO (1) | WO1999067192A2 (pl) |
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| US6599753B1 (en) * | 1998-06-24 | 2003-07-29 | Aventis Pharmaceuticals Inc. | Method and reagents for the quantification of solid-phase reactions using fluorine NMR |
| US6951958B1 (en) | 1999-08-03 | 2005-10-04 | Acadia Pharmaceuticals Inc. | Solid phase parallel synthesis of tertiary amines |
| AU2002213422A1 (en) | 2000-09-13 | 2002-03-26 | Georgetown University | Synthesis of 2-hydroxymethylglutamic acid and congeners thereof |
| US6888027B2 (en) * | 2000-09-29 | 2005-05-03 | Topotarget Uk Limited | Carbamic acid compounds comprising a sulfonamide linkage as HDAC inhibitors |
| US7235688B1 (en) | 2004-11-04 | 2007-06-26 | University Of Notre Dame Du Lac | Process for preparing histone deacetylase inhibitors and intermediates thereof |
| US20070021612A1 (en) * | 2004-11-04 | 2007-01-25 | University Of Notre Dame Du Lac | Processes and compounds for preparing histone deacetylase inhibitors and intermediates thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4507433A (en) * | 1983-10-07 | 1985-03-26 | The Johns Hopkins University | Preparation of oligodeoxyribonucleoside alkyl or arylphosphonates |
| US5783682A (en) * | 1990-07-27 | 1998-07-21 | Isis Pharmaceuticals, Inc. | Oligonucleotide mimics having nitrogen-containing linkages |
| GB9503749D0 (en) * | 1995-02-24 | 1995-04-12 | British Biotech Pharm | Synthesis of hydroxamic acid derivatives |
| ES2217386T3 (es) * | 1996-01-02 | 2004-11-01 | Aventis Pharmaceuticals Inc. | Compuestos de acido(aril, heteroaril, arilmetil o heteroarilmetil) hidroxamico sustituido. |
| ES2187800T3 (es) * | 1996-08-05 | 2003-06-16 | Prolinx Inc | Reactivos formadores de complejos con compuestos boronicos y complejos correspondientes. |
| DE19635768A1 (de) * | 1996-09-04 | 1998-03-05 | Ernst Prof Dr Bayer | Methacryloyl-Gruppen enthaltende polymere Trägersysteme, Verfahren zu ihrer Herstellung und ihre Verwendung in Festphasenreaktionen |
| WO1998018754A1 (en) * | 1996-10-28 | 1998-05-07 | Versicor, Inc. | Methods for solid-phase synthesis of hydroxylamine compounds and derivatives, and combinatorial libraries thereof |
| CN1238323C (zh) * | 1996-12-19 | 2006-01-25 | 阿温蒂斯药物公司 | 醛,酮,肟,胺和异羟肟酸化合物的固相合成方法 |
| CO5011072A1 (es) * | 1997-12-05 | 2001-02-28 | Lilly Co Eli | Etanolaminas pirazinil substituidas como agfonistas de los receptores |
| AU2495499A (en) * | 1998-02-17 | 1999-08-30 | Chembridge Corporation | Supports for solid state chemical reactions and method of use thereof |
-
1998
- 1998-06-24 US US09/103,872 patent/US6133409A/en not_active Expired - Fee Related
-
1999
- 1999-06-23 WO PCT/US1999/014251 patent/WO1999067192A2/en not_active Ceased
- 1999-06-23 KR KR1020007014744A patent/KR100734157B1/ko not_active Expired - Fee Related
- 1999-06-23 EA EA200100072A patent/EA004741B1/ru not_active IP Right Cessation
- 1999-06-23 CN CN99807689A patent/CN1307553A/zh active Pending
- 1999-06-23 CN CNA2005100965693A patent/CN1769318A/zh active Pending
- 1999-06-23 JP JP2000555848A patent/JP4070407B2/ja not_active Expired - Fee Related
- 1999-06-23 CA CA002335511A patent/CA2335511A1/en not_active Abandoned
- 1999-06-23 IL IL13979699A patent/IL139796A0/xx unknown
- 1999-06-23 CN CNB2005100965706A patent/CN100360580C/zh not_active Expired - Fee Related
- 1999-06-23 PL PL345494A patent/PL199122B1/pl unknown
- 1999-06-23 EP EP03076717A patent/EP1359136A3/en not_active Withdrawn
- 1999-06-23 EP EP06075267A patent/EP1688406A3/en not_active Withdrawn
- 1999-06-23 HU HU0102856A patent/HUP0102856A3/hu not_active Application Discontinuation
- 1999-06-23 BR BR9911499-2A patent/BR9911499A/pt not_active Application Discontinuation
- 1999-06-23 AP APAP/P/2000/001994A patent/AP2000001994A0/en unknown
- 1999-06-23 SK SK2014-2000A patent/SK20142000A3/sk unknown
- 1999-06-23 OA OA1200000355A patent/OA11773A/en unknown
- 1999-06-23 UA UA2001010533A patent/UA71917C2/uk unknown
- 1999-06-23 EP EP99930627A patent/EP1089958A4/en not_active Withdrawn
-
2000
- 2000-11-20 IL IL139796A patent/IL139796A/en not_active IP Right Cessation
- 2000-12-21 NO NO20006566A patent/NO20006566L/no not_active Application Discontinuation
-
2001
- 2001-01-18 BG BG105166A patent/BG65311B1/bg unknown
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