NO328890B1 - Pyrrolopyrimidiner, anvendelse derav og farmasoytisk sammensetning omfattende en slik forbindelse - Google Patents

Info

Publication number

NO328890B1

NO328890B1 NO20041180A NO20041180A NO328890B1 NO 328890 B1 NO328890 B1 NO 328890B1 NO 20041180 A NO20041180 A NO 20041180A NO 20041180 A NO20041180 A NO 20041180A NO 328890 B1 NO328890 B1 NO 328890B1

Authority

NO

Norway

Prior art keywords

dimethyl

propyl

carbonitrile

pyrrolo

pyrimidine

Prior art date

2001-08-30

Links

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• 150000001875 compounds Chemical class 0.000 title claims description 193
• 239000008194 pharmaceutical composition Substances 0.000 title claims description 5
• 150000004944 pyrrolopyrimidines Chemical class 0.000 title description 2
• -1 carboxy, formyl Chemical group 0.000 claims description 265
• IIHQNAXFIODVDU-UHFFFAOYSA-N pyrimidine-2-carbonitrile Chemical compound N#CC1=NC=CC=N1 IIHQNAXFIODVDU-UHFFFAOYSA-N 0.000 claims description 78
• 125000000217 alkyl group Chemical group 0.000 claims description 74
• LELOWRISYMNNSU-UHFFFAOYSA-N Hydrocyanic acid Natural products N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 claims description 45
• 125000003118 aryl group Chemical group 0.000 claims description 37
• 125000003545 alkoxy group Chemical group 0.000 claims description 29
• 229910052736 halogen Inorganic materials 0.000 claims description 27
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 27
• 150000002367 halogens Chemical class 0.000 claims description 25
• 238000002360 preparation method Methods 0.000 claims description 24
• 150000003839 salts Chemical class 0.000 claims description 22
• 229920006395 saturated elastomer Polymers 0.000 claims description 21
• 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 20
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 20
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 19
• 125000001424 substituent group Chemical group 0.000 claims description 19
• 125000005843 halogen group Chemical group 0.000 claims description 17
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 17
• 102000004171 Cathepsin K Human genes 0.000 claims description 16
• 108090000625 Cathepsin K Proteins 0.000 claims description 16
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 15
• 201000010099 disease Diseases 0.000 claims description 14
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 13
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 12
• 229910020008 S(O) Inorganic materials 0.000 claims description 12
• 125000004432 carbon atom Chemical group C* 0.000 claims description 12
• 125000000623 heterocyclic group Chemical group 0.000 claims description 12
• 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 12
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 11
• 125000004104 aryloxy group Chemical group 0.000 claims description 10
• 125000004043 oxo group Chemical group O=* 0.000 claims description 10
• 125000003435 aroyl group Chemical group 0.000 claims description 9
• 150000002148 esters Chemical class 0.000 claims description 9
• CYJAWBVQRMVFEO-UHFFFAOYSA-N piperazine-2,6-dione Chemical compound O=C1CNCC(=O)N1 CYJAWBVQRMVFEO-UHFFFAOYSA-N 0.000 claims description 9
• IZXIZTKNFFYFOF-UHFFFAOYSA-N 2-Oxazolidone Chemical compound O=C1NCCO1 IZXIZTKNFFYFOF-UHFFFAOYSA-N 0.000 claims description 8
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 8
• 125000005842 heteroatom Chemical group 0.000 claims description 8
• WJRBRSLFGCUECM-UHFFFAOYSA-N hydantoin Chemical compound O=C1CNC(=O)N1 WJRBRSLFGCUECM-UHFFFAOYSA-N 0.000 claims description 8
• 229940091173 hydantoin Drugs 0.000 claims description 8
• 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 8
• XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 claims description 8
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 7
• 125000005530 alkylenedioxy group Chemical group 0.000 claims description 6
• 229910052757 nitrogen Inorganic materials 0.000 claims description 6
• 125000004076 pyridyl group Chemical group 0.000 claims description 6
• 229910052717 sulfur Inorganic materials 0.000 claims description 6
• 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 5
• 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 5
• 229910052760 oxygen Inorganic materials 0.000 claims description 5
• 238000011321 prophylaxis Methods 0.000 claims description 5
• KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 4
• 125000002947 alkylene group Chemical group 0.000 claims description 4
• 125000003368 amide group Chemical group 0.000 claims description 4
• 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 4
• 229910052799 carbon Inorganic materials 0.000 claims description 4
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
• 125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 claims description 4
• 125000001425 triazolyl group Chemical group 0.000 claims description 4
• 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims description 3
• 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 3
• 125000002619 bicyclic group Chemical group 0.000 claims description 3
• 125000002883 imidazolyl group Chemical group 0.000 claims description 3
• 125000003831 tetrazolyl group Chemical group 0.000 claims description 3
• 125000001544 thienyl group Chemical group 0.000 claims description 3
• ORLCYMQZIPSODD-UHFFFAOYSA-N 1-chloro-2-[chloro(2,2,2-trichloroethoxy)phosphoryl]oxybenzene Chemical compound ClC1=CC=CC=C1OP(Cl)(=O)OCC(Cl)(Cl)Cl ORLCYMQZIPSODD-UHFFFAOYSA-N 0.000 claims description 2
• 125000004938 5-pyridyl group Chemical group N1=CC=CC(=C1)* 0.000 claims description 2
• AUNXAUMTLBKWDN-UHFFFAOYSA-N 6-[[4-[2-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl]piperazin-1-yl]methyl]-7-(2-methylpropyl)pyrrolo[2,3-d]pyrimidine-2-carbonitrile Chemical compound C=1C2=CN=C(C#N)N=C2N(CC(C)C)C=1CN(CC1)CCN1C1=CC=CC=C1OCCN1CCN(C)CC1 AUNXAUMTLBKWDN-UHFFFAOYSA-N 0.000 claims description 2
• HOLAMNFRWUTIPH-UHFFFAOYSA-N 6-[[4-[3-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl]piperazin-1-yl]methyl]-7-(2-methylpropyl)pyrrolo[2,3-d]pyrimidine-2-carbonitrile Chemical compound C=1C2=CN=C(C#N)N=C2N(CC(C)C)C=1CN(CC1)CCN1C(C=1)=CC=CC=1OCCN1CCN(C)CC1 HOLAMNFRWUTIPH-UHFFFAOYSA-N 0.000 claims description 2
• GIGXDLIAJGQRAQ-UHFFFAOYSA-N 6-[[4-[3-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl]piperidin-1-yl]methyl]-7-(2-methylpropyl)pyrrolo[2,3-d]pyrimidine-2-carbonitrile Chemical compound C=1C2=CN=C(C#N)N=C2N(CC(C)C)C=1CN(CC1)CCC1C(C=1)=CC=CC=1OCCN1CCN(C)CC1 GIGXDLIAJGQRAQ-UHFFFAOYSA-N 0.000 claims description 2
• MXALDIZMZILEHT-UHFFFAOYSA-N 6-[[4-[3-[3-(4-methylpiperazin-1-yl)propoxy]phenyl]piperidin-1-yl]methyl]-7-(2-methylpropyl)pyrrolo[2,3-d]pyrimidine-2-carbonitrile Chemical compound C=1C2=CN=C(C#N)N=C2N(CC(C)C)C=1CN(CC1)CCC1C(C=1)=CC=CC=1OCCCN1CCN(C)CC1 MXALDIZMZILEHT-UHFFFAOYSA-N 0.000 claims description 2
• FNPBVCDOFHULAQ-UHFFFAOYSA-N 6-[[4-[4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl]piperazin-1-yl]methyl]-7-(2-methylpropyl)pyrrolo[2,3-d]pyrimidine-2-carbonitrile Chemical group C=1C2=CN=C(C#N)N=C2N(CC(C)C)C=1CN(CC1)CCN1C(C=C1)=CC=C1OCCN1CCN(C)CC1 FNPBVCDOFHULAQ-UHFFFAOYSA-N 0.000 claims description 2
• OPSCDEKVNNNUFM-UHFFFAOYSA-N 6-[[4-[4-[2-(dimethylamino)ethoxy]phenyl]piperidin-1-yl]methyl]-7-(2,2-dimethylpropyl)pyrrolo[2,3-d]pyrimidine-2-carbonitrile Chemical compound C1=CC(OCCN(C)C)=CC=C1C1CCN(CC=2N(C3=NC(=NC=C3C=2)C#N)CC(C)(C)C)CC1 OPSCDEKVNNNUFM-UHFFFAOYSA-N 0.000 claims description 2
• LMHQISUNQXUKHX-UHFFFAOYSA-N 7-(2,2-dimethylpropyl)-6-[[4-[2-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl]piperidin-1-yl]methyl]pyrrolo[2,3-d]pyrimidine-2-carbonitrile Chemical compound C1CN(C)CCN1CCOC1=CC=CC=C1C1CCN(CC=2N(C3=NC(=NC=C3C=2)C#N)CC(C)(C)C)CC1 LMHQISUNQXUKHX-UHFFFAOYSA-N 0.000 claims description 2
• QVMOSOJJSBKNLJ-UHFFFAOYSA-N 7-(2,2-dimethylpropyl)-6-[[4-[2-[3-(4-methylpiperazin-1-yl)propoxy]phenyl]piperidin-1-yl]methyl]pyrrolo[2,3-d]pyrimidine-2-carbonitrile Chemical compound C1CN(C)CCN1CCCOC1=CC=CC=C1C1CCN(CC=2N(C3=NC(=NC=C3C=2)C#N)CC(C)(C)C)CC1 QVMOSOJJSBKNLJ-UHFFFAOYSA-N 0.000 claims description 2
• AOGHZCDVVFVDEP-UHFFFAOYSA-N 7-(2,2-dimethylpropyl)-6-[[4-[3-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl]piperidin-1-yl]methyl]pyrrolo[2,3-d]pyrimidine-2-carbonitrile Chemical compound C1CN(C)CCN1CCOC1=CC=CC(C2CCN(CC=3N(C4=NC(=NC=C4C=3)C#N)CC(C)(C)C)CC2)=C1 AOGHZCDVVFVDEP-UHFFFAOYSA-N 0.000 claims description 2
• KNUDRFYJFMJIEO-UHFFFAOYSA-N 7-(2,2-dimethylpropyl)-6-[[4-[3-[3-(4-methylpiperazin-1-yl)propoxy]phenyl]piperidin-1-yl]methyl]pyrrolo[2,3-d]pyrimidine-2-carbonitrile Chemical compound C1CN(C)CCN1CCCOC1=CC=CC(C2CCN(CC=3N(C4=NC(=NC=C4C=3)C#N)CC(C)(C)C)CC2)=C1 KNUDRFYJFMJIEO-UHFFFAOYSA-N 0.000 claims description 2
• PYBRNWJJSLVOSI-UHFFFAOYSA-N 7-(2,2-dimethylpropyl)-6-[[4-[4-(2-pyrrolidin-1-ylethoxy)phenyl]piperidin-1-yl]methyl]pyrrolo[2,3-d]pyrimidine-2-carbonitrile Chemical compound C=1C2=CN=C(C#N)N=C2N(CC(C)(C)C)C=1CN(CC1)CCC1C(C=C1)=CC=C1OCCN1CCCC1 PYBRNWJJSLVOSI-UHFFFAOYSA-N 0.000 claims description 2
• OUUAIGGCPYHJKU-UHFFFAOYSA-N 7-(2,2-dimethylpropyl)-6-[[4-[4-[3-(4-methylpiperazin-1-yl)propoxy]phenyl]piperidin-1-yl]methyl]pyrrolo[2,3-d]pyrimidine-2-carbonitrile Chemical compound C1CN(C)CCN1CCCOC1=CC=C(C2CCN(CC=3N(C4=NC(=NC=C4C=3)C#N)CC(C)(C)C)CC2)C=C1 OUUAIGGCPYHJKU-UHFFFAOYSA-N 0.000 claims description 2
• MAFAZFPSXCIMMT-UHFFFAOYSA-N 7-(2-methylpropyl)-6-[[4-[4-(2-pyrrolidin-1-ylethoxy)phenyl]piperidin-1-yl]methyl]pyrrolo[2,3-d]pyrimidine-2-carbonitrile Chemical compound C=1C2=CN=C(C#N)N=C2N(CC(C)C)C=1CN(CC1)CCC1C(C=C1)=CC=C1OCCN1CCCC1 MAFAZFPSXCIMMT-UHFFFAOYSA-N 0.000 claims description 2
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 2
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 2
• 239000004480 active ingredient Substances 0.000 claims description 2
• 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 2
• 125000004619 benzopyranyl group Chemical group O1C(C=CC2=C1C=CC=C2)* 0.000 claims description 2
• 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 2
• 125000004600 benzothiopyranyl group Chemical group S1C(C=CC2=C1C=CC=C2)* 0.000 claims description 2
• QDHFHIQKOVNCNC-UHFFFAOYSA-N butane-1-sulfonic acid Chemical compound CCCCS(O)(=O)=O QDHFHIQKOVNCNC-UHFFFAOYSA-N 0.000 claims description 2
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 2
• 239000003814 drug Substances 0.000 claims description 2
• 125000002541 furyl group Chemical group 0.000 claims description 2
• 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 2
• 125000000842 isoxazolyl group Chemical group 0.000 claims description 2
• 125000002971 oxazolyl group Chemical group 0.000 claims description 2
• 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 2
• 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 claims description 2
• 125000003226 pyrazolyl group Chemical group 0.000 claims description 2
• 125000000168 pyrrolyl group Chemical group 0.000 claims description 2
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 2
• 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims description 2
• 125000006413 ring segment Chemical group 0.000 claims description 2
• 125000003003 spiro group Chemical group 0.000 claims description 2
• 238000006467 substitution reaction Methods 0.000 claims description 2
• 230000001225 therapeutic effect Effects 0.000 claims description 2
• 125000000335 thiazolyl group Chemical group 0.000 claims description 2
• HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 claims 2
• XCLCHALZLMRKMQ-UHFFFAOYSA-N 6-[(6-chloropyrimidin-4-yl)oxymethyl]-7-(2,2-dimethylpropyl)pyrrolo[2,3-d]pyrimidine-2-carbonitrile Chemical compound C=1C2=CN=C(C#N)N=C2N(CC(C)(C)C)C=1COC1=CC(Cl)=NC=N1 XCLCHALZLMRKMQ-UHFFFAOYSA-N 0.000 claims 1
• CDZBRYFIHGHOAJ-UHFFFAOYSA-N 6-[[4-(2,4-dimethoxyphenyl)piperidin-1-yl]methyl]-7-(2,2-dimethylpropyl)pyrrolo[2,3-d]pyrimidine-2-carbonitrile Chemical compound COC1=CC(OC)=CC=C1C1CCN(CC=2N(C3=NC(=NC=C3C=2)C#N)CC(C)(C)C)CC1 CDZBRYFIHGHOAJ-UHFFFAOYSA-N 0.000 claims 1
• ZDJLKHADBWOJQU-UHFFFAOYSA-N 7-(2,2-dimethylpropyl)-6-[(1-ethyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)methyl]pyrrolo[2,3-d]pyrimidine-2-carbonitrile Chemical compound CCN1C(=O)NC(=O)C11CCN(CC=2N(C3=NC(=NC=C3C=2)C#N)CC(C)(C)C)CC1 ZDJLKHADBWOJQU-UHFFFAOYSA-N 0.000 claims 1
• GXOJVJRVBSWEIY-UHFFFAOYSA-N 7-(2,2-dimethylpropyl)-6-[(1-methyl-2,4-dioxo-3-propyl-1,3,8-triazaspiro[4.5]decan-8-yl)methyl]pyrrolo[2,3-d]pyrimidine-2-carbonitrile Chemical compound O=C1N(CCC)C(=O)N(C)C11CCN(CC=2N(C3=NC(=NC=C3C=2)C#N)CC(C)(C)C)CC1 GXOJVJRVBSWEIY-UHFFFAOYSA-N 0.000 claims 1
• ZUFKLYQKICZFHV-UHFFFAOYSA-N 7-(2,2-dimethylpropyl)-6-[[4-[2-(2-pyrrolidin-1-ylethoxy)phenyl]piperidin-1-yl]methyl]pyrrolo[2,3-d]pyrimidine-2-carbonitrile Chemical compound C=1C2=CN=C(C#N)N=C2N(CC(C)(C)C)C=1CN(CC1)CCC1C1=CC=CC=C1OCCN1CCCC1 ZUFKLYQKICZFHV-UHFFFAOYSA-N 0.000 claims 1
• XYPKNCIOPIPZEG-UHFFFAOYSA-N 8-(bromomethyl)-9-(2,2-dimethylpropyl)purine-2-carbonitrile Chemical compound N1=C(C#N)N=C2N(CC(C)(C)C)C(CBr)=NC2=C1 XYPKNCIOPIPZEG-UHFFFAOYSA-N 0.000 claims 1
• JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims 1
• DNSISZSEWVHGLH-UHFFFAOYSA-N butanamide Chemical compound CCCC(N)=O DNSISZSEWVHGLH-UHFFFAOYSA-N 0.000 claims 1
• 150000001732 carboxylic acid derivatives Chemical class 0.000 claims 1
• ZCRZCMUDOWDGOB-UHFFFAOYSA-N ethanesulfonimidic acid Chemical compound CCS(N)(=O)=O ZCRZCMUDOWDGOB-UHFFFAOYSA-N 0.000 claims 1
• 125000001041 indolyl group Chemical group 0.000 claims 1
• JDVPQXZIJDEHAN-UHFFFAOYSA-N succinamic acid Chemical compound NC(=O)CCC(O)=O JDVPQXZIJDEHAN-UHFFFAOYSA-N 0.000 claims 1
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 336
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 291
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 195
• 239000000203 mixture Substances 0.000 description 157
• 239000000243 solution Substances 0.000 description 131
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 116
• 238000005160 1H NMR spectroscopy Methods 0.000 description 114
• 239000012267 brine Substances 0.000 description 113
• 239000011541 reaction mixture Substances 0.000 description 113
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 113
• 239000000047 product Substances 0.000 description 86
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 81
• 229910001868 water Inorganic materials 0.000 description 72
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 71
• 239000000284 extract Substances 0.000 description 68
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 68
• 238000010898 silica gel chromatography Methods 0.000 description 67
• 238000000034 method Methods 0.000 description 62
• 239000012044 organic layer Substances 0.000 description 60
• 239000007858 starting material Substances 0.000 description 59
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 58
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 58
• 235000019341 magnesium sulphate Nutrition 0.000 description 58
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 54
• 230000002829 reductive effect Effects 0.000 description 52
• 238000006243 chemical reaction Methods 0.000 description 51
• 239000000741 silica gel Substances 0.000 description 51
• 229910002027 silica gel Inorganic materials 0.000 description 51
• 239000002904 solvent Substances 0.000 description 40
• RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 37
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 35
• 229910000027 potassium carbonate Inorganic materials 0.000 description 35
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 34
• 235000019439 ethyl acetate Nutrition 0.000 description 34
• 229910052938 sodium sulfate Inorganic materials 0.000 description 34
• 235000011152 sodium sulphate Nutrition 0.000 description 34
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 33
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 26
• 239000012299 nitrogen atmosphere Substances 0.000 description 25
• SVNIABUZGXNWNA-UHFFFAOYSA-N 6-(bromomethyl)-7-(2,2-dimethylpropyl)pyrrolo[2,3-d]pyrimidine-2-carbonitrile Chemical compound N1=C(C#N)N=C2N(CC(C)(C)C)C(CBr)=CC2=C1 SVNIABUZGXNWNA-UHFFFAOYSA-N 0.000 description 24
• 235000011181 potassium carbonates Nutrition 0.000 description 24
• 238000003756 stirring Methods 0.000 description 23
• 239000012043 crude product Substances 0.000 description 22
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 21
• 239000000725 suspension Substances 0.000 description 20
• 238000004440 column chromatography Methods 0.000 description 19
• 238000000746 purification Methods 0.000 description 19
• DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 18
• 239000003480 eluent Substances 0.000 description 16
• 239000007787 solid Substances 0.000 description 16
• 238000004587 chromatography analysis Methods 0.000 description 15
• 239000000706 filtrate Substances 0.000 description 15
• 238000001816 cooling Methods 0.000 description 13
• 238000001704 evaporation Methods 0.000 description 13
• 230000008020 evaporation Effects 0.000 description 13
• 239000005457 ice water Substances 0.000 description 13
• 239000011734 sodium Substances 0.000 description 13
• WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 13
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