CA2494848A1

CA2494848A1 - Urea derivatives as kinase inhibitors

Urea derivatives as kinase inhibitors Download PDF

Info

Publication number: CA2494848A1
Authority: CA; Canada
Prior art keywords: cyano; pyrazinyl; urea; phenyl; chloro
Prior art date: 2002-08-13
Legal status : Abandoned

Application number

CA002494848A

Other languages

English (en)

French (fr)

Inventor

Goaquan Li

Qun Li

Tongmei Li

Nan-Horng Lin

Robert A. Mantei

Hing L. Sham

Gary T. Wang

Current Assignee

Abbott Laboratories

Original Assignee

Individual

Priority date

2002-08-13

Filing date

2003-08-05

Publication date

2004-02-19

2003-08-05 Application filed by Individual filed Critical Individual

2004-02-19 Publication of CA2494848A1 publication Critical patent/CA2494848A1/en

Status Abandoned legal-status Critical Current

Links

229940043355 kinase inhibitor Drugs 0.000 title description 2
239000003757 phosphotransferase inhibitor Substances 0.000 title description 2
150000003672 ureas Chemical class 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 153
238000000034 method Methods 0.000 claims abstract description 25
102000001253 Protein Kinase Human genes 0.000 claims abstract description 8
108060006633 protein kinase Proteins 0.000 claims abstract description 8
230000002401 inhibitory effect Effects 0.000 claims abstract description 5
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 124
125000000217 alkyl group Chemical group 0.000 claims description 75
239000004202 carbamide Substances 0.000 claims description 63
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 40
-1 amino, carboxy Chemical group 0.000 claims description 33
125000000753 cycloalkyl group Chemical group 0.000 claims description 29
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 29
229910052739 hydrogen Inorganic materials 0.000 claims description 27
239000001257 hydrogen Substances 0.000 claims description 27
125000000623 heterocyclic group Chemical group 0.000 claims description 23
125000004183 alkoxy alkyl group Chemical group 0.000 claims description 21
125000000392 cycloalkenyl group Chemical group 0.000 claims description 21
125000003118 aryl group Chemical group 0.000 claims description 20
125000004093 cyano group Chemical group *C#N 0.000 claims description 19
125000003545 alkoxy group Chemical group 0.000 claims description 17
125000002768 hydroxyalkyl group Chemical group 0.000 claims description 17
125000003342 alkenyl group Chemical group 0.000 claims description 16
125000004103 aminoalkyl group Chemical group 0.000 claims description 14
125000003710 aryl alkyl group Chemical group 0.000 claims description 14
150000003839 salts Chemical class 0.000 claims description 14
125000001072 heteroaryl group Chemical group 0.000 claims description 13
125000004686 alkyl sulfanyl alkyl group Chemical group 0.000 claims description 12
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 11
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 11
125000001188 haloalkyl group Chemical group 0.000 claims description 9
206010028980 Neoplasm Diseases 0.000 claims description 8
125000000304 alkynyl group Chemical group 0.000 claims description 7
125000004446 heteroarylalkyl group Chemical group 0.000 claims description 6
125000005081 alkoxyalkoxyalkyl group Chemical group 0.000 claims description 5
125000005078 alkoxycarbonylalkyl group Chemical group 0.000 claims description 4
125000004448 alkyl carbonyl group Chemical group 0.000 claims description 4
125000005160 aryl oxy alkyl group Chemical group 0.000 claims description 4
201000011510 cancer Diseases 0.000 claims description 4
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 3
239000008194 pharmaceutical composition Substances 0.000 claims description 3
PVAQILHDQHGVSP-UHFFFAOYSA-N 1-(5-chloro-2-cyclohex-2-en-1-yloxyphenyl)-3-(5-cyanopyrazin-2-yl)urea Chemical compound C=1N=C(C#N)C=NC=1NC(=O)NC1=CC(Cl)=CC=C1OC1CCCC=C1 PVAQILHDQHGVSP-UHFFFAOYSA-N 0.000 claims description 2
SECWPIJSHYOZKM-UHFFFAOYSA-N 1-[5-chloro-2-(1-ethoxypropan-2-yloxy)phenyl]-3-(5-cyanopyrazin-2-yl)urea Chemical compound CCOCC(C)OC1=CC=C(Cl)C=C1NC(=O)NC1=CN=C(C#N)C=N1 SECWPIJSHYOZKM-UHFFFAOYSA-N 0.000 claims description 2
FHKIBVIDIBQHBF-UHFFFAOYSA-N 1-[5-chloro-2-(1-methoxypropan-2-yloxy)phenyl]-3-(5-cyanopyrazin-2-yl)urea Chemical compound COCC(C)OC1=CC=C(Cl)C=C1NC(=O)NC1=CN=C(C#N)C=N1 FHKIBVIDIBQHBF-UHFFFAOYSA-N 0.000 claims description 2
LXKNXVQJYTVJID-UHFFFAOYSA-N 1-[5-chloro-2-(2-ethoxyethoxy)phenyl]-3-(5-cyanopyrazin-2-yl)urea Chemical compound CCOCCOC1=CC=C(Cl)C=C1NC(=O)NC1=CN=C(C#N)C=N1 LXKNXVQJYTVJID-UHFFFAOYSA-N 0.000 claims description 2
QUQIALMRPMENGJ-UHFFFAOYSA-N 1-[5-chloro-2-(2-propan-2-yloxyethoxy)phenyl]-3-(5-cyanopyrazin-2-yl)urea Chemical compound CC(C)OCCOC1=CC=C(Cl)C=C1NC(=O)NC1=CN=C(C#N)C=N1 QUQIALMRPMENGJ-UHFFFAOYSA-N 0.000 claims description 2
125000001844 prenyl group Chemical group [H]C([*])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
125000001475 halogen functional group Chemical group 0.000 claims 3
101100244083 Arabidopsis thaliana PKL gene Proteins 0.000 claims 2
SWAAOLKRNXQREI-UHFFFAOYSA-N 1-(5-chloro-2-pent-3-ynoxyphenyl)-3-(5-cyanopyrazin-2-yl)urea Chemical compound CC#CCCOC1=CC=C(Cl)C=C1NC(=O)NC1=CN=C(C#N)C=N1 SWAAOLKRNXQREI-UHFFFAOYSA-N 0.000 claims 1
BMZFLFKIZNBUFB-UHFFFAOYSA-N 1-(5-chloro-2-phenacyloxyphenyl)-3-(5-cyanopyrazin-2-yl)urea Chemical compound C=1N=C(C#N)C=NC=1NC(=O)NC1=CC(Cl)=CC=C1OCC(=O)C1=CC=CC=C1 BMZFLFKIZNBUFB-UHFFFAOYSA-N 0.000 claims 1
LYRRMGQXNDNVPS-UHFFFAOYSA-N 1-[2-(3-aminopropoxy)-5-chlorophenyl]-3-(5-cyanopyrazin-2-yl)urea Chemical compound NCCCOC1=CC=C(Cl)C=C1NC(=O)NC1=CN=C(C#N)C=N1 LYRRMGQXNDNVPS-UHFFFAOYSA-N 0.000 claims 1
XYCSIMKFHRSWBS-UHFFFAOYSA-N 1-[2-[2-(4-bromophenoxy)ethoxy]-5-chlorophenyl]-3-(5-cyanopyrazin-2-yl)urea Chemical compound C=1N=C(C#N)C=NC=1NC(=O)NC1=CC(Cl)=CC=C1OCCOC1=CC=C(Br)C=C1 XYCSIMKFHRSWBS-UHFFFAOYSA-N 0.000 claims 1
CWTLRICITVFRIL-RFHHWMCGSA-N 1-[2-[[(1s,4s)-3-bicyclo[2.2.1]heptanyl]methoxy]-5-chlorophenyl]-3-(5-cyanopyrazin-2-yl)urea Chemical compound C1([C@@]2([H])CC[C@@](C2)(C1)[H])COC1=CC=C(Cl)C=C1NC(=O)NC1=CN=C(C#N)C=N1 CWTLRICITVFRIL-RFHHWMCGSA-N 0.000 claims 1
UOVQGCMOPSZGOP-UHFFFAOYSA-N 1-[2-[benzyl(2-hydroxyethyl)amino]-5-bromophenyl]-3-(5-cyanopyrazin-2-yl)urea Chemical compound C=1C=C(Br)C=C(NC(=O)NC=2N=CC(=NC=2)C#N)C=1N(CCO)CC1=CC=CC=C1 UOVQGCMOPSZGOP-UHFFFAOYSA-N 0.000 claims 1
NSHVATFCXCSIAN-UHFFFAOYSA-N 1-[2-[benzyl(2-hydroxyethyl)amino]-5-chlorophenyl]-3-(5-cyanopyrazin-2-yl)urea Chemical compound C=1C=C(Cl)C=C(NC(=O)NC=2N=CC(=NC=2)C#N)C=1N(CCO)CC1=CC=CC=C1 NSHVATFCXCSIAN-UHFFFAOYSA-N 0.000 claims 1
FKQHZPMKUJQFBQ-UHFFFAOYSA-N 1-[2-[bis(2-methoxyethyl)amino]-5-bromophenyl]-3-(5-cyanopyrazin-2-yl)urea Chemical compound COCCN(CCOC)C1=CC=C(Br)C=C1NC(=O)NC1=CN=C(C#N)C=N1 FKQHZPMKUJQFBQ-UHFFFAOYSA-N 0.000 claims 1
NGJURHJPIBNKHP-UHFFFAOYSA-N 1-[2-[bis(2-methoxyethyl)amino]-5-chlorophenyl]-3-(5-cyanopyrazin-2-yl)urea Chemical compound COCCN(CCOC)C1=CC=C(Cl)C=C1NC(=O)NC1=CN=C(C#N)C=N1 NGJURHJPIBNKHP-UHFFFAOYSA-N 0.000 claims 1
ULABCUBILRGHSL-UHFFFAOYSA-N 1-[2-[bis(2-methoxyethyl)amino]-5-cyanophenyl]-3-(5-cyanopyrazin-2-yl)urea Chemical compound COCCN(CCOC)C1=CC=C(C#N)C=C1NC(=O)NC1=CN=C(C#N)C=N1 ULABCUBILRGHSL-UHFFFAOYSA-N 0.000 claims 1
YFTMNKQWOWZYPP-UHFFFAOYSA-N 1-[5-bromo-2-[(2-hydroxy-2-phenylethyl)-methylamino]phenyl]-3-(5-cyanopyrazin-2-yl)urea Chemical compound C=1C=C(Br)C=C(NC(=O)NC=2N=CC(=NC=2)C#N)C=1N(C)CC(O)C1=CC=CC=C1 YFTMNKQWOWZYPP-UHFFFAOYSA-N 0.000 claims 1
QXWXEJMOZMDALO-UHFFFAOYSA-N 1-[5-bromo-2-[ethyl(2-methoxyethyl)amino]phenyl]-3-(5-cyanopyrazin-2-yl)urea Chemical compound COCCN(CC)C1=CC=C(Br)C=C1NC(=O)NC1=CN=C(C#N)C=N1 QXWXEJMOZMDALO-UHFFFAOYSA-N 0.000 claims 1
BNNJQBBPHHAJAK-UHFFFAOYSA-N 1-[5-chloro-2-(2-chloro-1-methoxyethoxy)phenyl]-3-(5-cyanopyrazin-2-yl)urea Chemical compound COC(CCl)OC1=CC=C(Cl)C=C1NC(=O)NC1=CN=C(C#N)C=N1 BNNJQBBPHHAJAK-UHFFFAOYSA-N 0.000 claims 1
JBNRXWLOFSXQPH-UHFFFAOYSA-N 1-[5-chloro-2-(2-cyclohexylethoxy)phenyl]-3-(5-cyanopyrazin-2-yl)urea Chemical compound C=1N=C(C#N)C=NC=1NC(=O)NC1=CC(Cl)=CC=C1OCCC1CCCCC1 JBNRXWLOFSXQPH-UHFFFAOYSA-N 0.000 claims 1
MWFYFELKCFAENX-UHFFFAOYSA-N 1-[5-chloro-2-(2-methoxyethoxy)phenyl]-3-(5-cyanopyrazin-2-yl)urea Chemical compound COCCOC1=CC=C(Cl)C=C1NC(=O)NC1=CN=C(C#N)C=N1 MWFYFELKCFAENX-UHFFFAOYSA-N 0.000 claims 1
ATMLVTOWEJMISI-UHFFFAOYSA-N 1-[5-chloro-2-(2-methylsulfanylethoxy)phenyl]-3-(5-cyanopyrazin-2-yl)urea Chemical compound CSCCOC1=CC=C(Cl)C=C1NC(=O)NC1=CN=C(C#N)C=N1 ATMLVTOWEJMISI-UHFFFAOYSA-N 0.000 claims 1
NHLKQOYABMYRNX-UHFFFAOYSA-N 1-[5-chloro-2-(3-methoxy-3-methylbutoxy)phenyl]-3-(5-cyanopyrazin-2-yl)urea Chemical compound COC(C)(C)CCOC1=CC=C(Cl)C=C1NC(=O)NC1=CN=C(C#N)C=N1 NHLKQOYABMYRNX-UHFFFAOYSA-N 0.000 claims 1
WHSYXEUKLZRABI-UHFFFAOYSA-N 1-[5-chloro-2-(cyclopropylmethoxy)phenyl]-3-(5-cyanopyrazin-2-yl)urea Chemical compound C=1N=C(C#N)C=NC=1NC(=O)NC1=CC(Cl)=CC=C1OCC1CC1 WHSYXEUKLZRABI-UHFFFAOYSA-N 0.000 claims 1
SMZDIRCVFZTJOH-UHFFFAOYSA-N 1-[5-chloro-2-[(1-methylcyclopropyl)methoxy]phenyl]-3-(5-cyanopyrazin-2-yl)urea Chemical compound C=1C=C(Cl)C=C(NC(=O)NC=2N=CC(=NC=2)C#N)C=1OCC1(C)CC1 SMZDIRCVFZTJOH-UHFFFAOYSA-N 0.000 claims 1
QTKDJHMPFMGJMG-OLZOCXBDSA-N 1-[5-chloro-2-[(1s,3r)-3-hydroxycyclopentyl]oxyphenyl]-3-(5-cyanopyrazin-2-yl)urea Chemical compound C1[C@H](O)CC[C@@H]1OC1=CC=C(Cl)C=C1NC(=O)NC1=CN=C(C#N)C=N1 QTKDJHMPFMGJMG-OLZOCXBDSA-N 0.000 claims 1
XDROTNZAWWKOTD-UHFFFAOYSA-N 1-[5-chloro-2-[(2-hydroxy-2-phenylethyl)-methylamino]phenyl]-3-(5-cyanopyrazin-2-yl)urea Chemical compound C=1C=C(Cl)C=C(NC(=O)NC=2N=CC(=NC=2)C#N)C=1N(C)CC(O)C1=CC=CC=C1 XDROTNZAWWKOTD-UHFFFAOYSA-N 0.000 claims 1
WZDAKTSKZFOPJB-UHFFFAOYSA-N 1-[5-chloro-2-[(2-methylcyclopropyl)methoxy]phenyl]-3-(5-cyanopyrazin-2-yl)urea Chemical compound CC1CC1COC1=CC=C(Cl)C=C1NC(=O)NC1=CN=C(C#N)C=N1 WZDAKTSKZFOPJB-UHFFFAOYSA-N 0.000 claims 1
OPWDDEKZLIKNPN-LLVKDONJSA-N 1-[5-chloro-2-[(2r)-2,3-dihydroxypropoxy]phenyl]-3-(5-cyanopyrazin-2-yl)urea Chemical compound OC[C@@H](O)COC1=CC=C(Cl)C=C1NC(=O)NC1=CN=C(C#N)C=N1 OPWDDEKZLIKNPN-LLVKDONJSA-N 0.000 claims 1
OPWDDEKZLIKNPN-NSHDSACASA-N 1-[5-chloro-2-[(2s)-2,3-dihydroxypropoxy]phenyl]-3-(5-cyanopyrazin-2-yl)urea Chemical compound OC[C@H](O)COC1=CC=C(Cl)C=C1NC(=O)NC1=CN=C(C#N)C=N1 OPWDDEKZLIKNPN-NSHDSACASA-N 0.000 claims 1
URMCAXGZEZUWEG-QXMXGUDHSA-N 1-[5-chloro-2-[(3s,4r)-3,4-dihydroxycyclopentyl]oxyphenyl]-3-(5-cyanopyrazin-2-yl)urea Chemical compound C1[C@@H](O)[C@@H](O)CC1OC1=CC=C(Cl)C=C1NC(=O)NC1=CN=C(C#N)C=N1 URMCAXGZEZUWEG-QXMXGUDHSA-N 0.000 claims 1
IODANOYNIPFWFE-UHFFFAOYSA-N 1-[5-chloro-2-[1-(dimethylamino)propan-2-yloxy]phenyl]-3-(5-cyanopyrazin-2-yl)urea Chemical compound CN(C)CC(C)OC1=CC=C(Cl)C=C1NC(=O)NC1=CN=C(C#N)C=N1 IODANOYNIPFWFE-UHFFFAOYSA-N 0.000 claims 1
RRIUNYNGHUZZFO-UHFFFAOYSA-N 1-[5-chloro-2-[2-(2-methoxyethoxy)ethoxy]phenyl]-3-(5-cyanopyrazin-2-yl)urea Chemical compound COCCOCCOC1=CC=C(Cl)C=C1NC(=O)NC1=CN=C(C#N)C=N1 RRIUNYNGHUZZFO-UHFFFAOYSA-N 0.000 claims 1
WABCAIVLMXJPIS-UHFFFAOYSA-N 1-[5-chloro-2-[2-(n-ethyl-3-methylanilino)ethoxy]phenyl]-3-(5-cyanopyrazin-2-yl)urea Chemical compound C=1C=CC(C)=CC=1N(CC)CCOC1=CC=C(Cl)C=C1NC(=O)NC1=CN=C(C#N)C=N1 WABCAIVLMXJPIS-UHFFFAOYSA-N 0.000 claims 1
OEMOGAOWNWNMAR-UHFFFAOYSA-N 1-[5-chloro-2-[2-[3-(6-methylpyridin-2-yl)propoxy]ethoxy]phenyl]-3-(5-cyanopyrazin-2-yl)urea Chemical compound CC1=CC=CC(CCCOCCOC=2C(=CC(Cl)=CC=2)NC(=O)NC=2N=CC(=NC=2)C#N)=N1 OEMOGAOWNWNMAR-UHFFFAOYSA-N 0.000 claims 1
IALGTMKWTOGLGC-UHFFFAOYSA-N 1-[5-chloro-2-[2-[n-(2-cyanoethyl)anilino]ethoxy]phenyl]-3-(5-cyanopyrazin-2-yl)urea Chemical compound C=1N=C(C#N)C=NC=1NC(=O)NC1=CC(Cl)=CC=C1OCCN(CCC#N)C1=CC=CC=C1 IALGTMKWTOGLGC-UHFFFAOYSA-N 0.000 claims 1
GBSMMFHITBMOIH-UHFFFAOYSA-N 1-[5-chloro-2-[3-(dimethylamino)propoxy]phenyl]-3-(5-cyanopyrazin-2-yl)urea Chemical compound CN(C)CCCOC1=CC=C(Cl)C=C1NC(=O)NC1=CN=C(C#N)C=N1 GBSMMFHITBMOIH-UHFFFAOYSA-N 0.000 claims 1
FWFZPSCKCHHLCM-UHFFFAOYSA-N 1-[5-chloro-2-[ethyl(2-methoxyethyl)amino]phenyl]-3-(5-cyanopyrazin-2-yl)urea Chemical compound COCCN(CC)C1=CC=C(Cl)C=C1NC(=O)NC1=CN=C(C#N)C=N1 FWFZPSCKCHHLCM-UHFFFAOYSA-N 0.000 claims 1
BDCPPOFQGALGOU-UHFFFAOYSA-N 1-[5-cyano-2-[(2-hydroxy-2-phenylethyl)-methylamino]phenyl]-3-(5-cyanopyrazin-2-yl)urea Chemical compound C=1C=C(C#N)C=C(NC(=O)NC=2N=CC(=NC=2)C#N)C=1N(C)CC(O)C1=CC=CC=C1 BDCPPOFQGALGOU-UHFFFAOYSA-N 0.000 claims 1
UQHOXOXVMZRAHT-UHFFFAOYSA-N ethyl 2-[[4-chloro-2-[(5-cyanopyrazin-2-yl)carbamoylamino]phenoxy]methyl]cyclopropane-1-carboxylate Chemical compound CCOC(=O)C1CC1COC1=CC=C(Cl)C=C1NC(=O)NC1=CN=C(C#N)C=N1 UQHOXOXVMZRAHT-UHFFFAOYSA-N 0.000 claims 1
UMSJTLJUVVWWKE-UHFFFAOYSA-N ethyl 6-[4-chloro-2-[(5-cyanopyrazin-2-yl)carbamoylamino]phenoxy]hexanoate Chemical compound CCOC(=O)CCCCCOC1=CC=C(Cl)C=C1NC(=O)NC1=CN=C(C#N)C=N1 UMSJTLJUVVWWKE-UHFFFAOYSA-N 0.000 claims 1
125000004356 hydroxy functional group Chemical group O* 0.000 claims 1
239000000203 mixture Substances 0.000 abstract description 32
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 90
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 63
239000000047 product Substances 0.000 description 60
238000005160 1H NMR spectroscopy Methods 0.000 description 49
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 36
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 30
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 26
238000006243 chemical reaction Methods 0.000 description 23
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 22
239000000243 solution Substances 0.000 description 22
239000012141 concentrate Substances 0.000 description 21
235000008504 concentrate Nutrition 0.000 description 21
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 19
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 15
125000002887 hydroxy group Chemical group [H]O* 0.000 description 14
125000002950 monocyclic group Chemical group 0.000 description 14
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
125000005843 halogen group Chemical group 0.000 description 12
239000000741 silica gel Substances 0.000 description 12
229910002027 silica gel Inorganic materials 0.000 description 12
150000002431 hydrogen Chemical class 0.000 description 11
239000002904 solvent Substances 0.000 description 10
IBZKBSXREAQDTO-UHFFFAOYSA-N 2-methoxy-n-(2-methoxyethyl)ethanamine Chemical compound COCCNCCOC IBZKBSXREAQDTO-UHFFFAOYSA-N 0.000 description 9
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 9
238000003818 flash chromatography Methods 0.000 description 9
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 9
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 8
238000010521 absorption reaction Methods 0.000 description 8
125000004414 alkyl thio group Chemical group 0.000 description 8
125000002619 bicyclic group Chemical group 0.000 description 8
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 8
125000001424 substituent group Chemical group 0.000 description 8
101150006084 CHKB gene Proteins 0.000 description 7
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 7
125000004453 alkoxycarbonyl group Chemical group 0.000 description 7
125000004966 cyanoalkyl group Chemical group 0.000 description 7
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 7
125000004971 nitroalkyl group Chemical group 0.000 description 7
108091000080 Phosphotransferase Proteins 0.000 description 6
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
125000004438 haloalkoxy group Chemical group 0.000 description 6
125000004430 oxygen atom Chemical group O* 0.000 description 6
102000020233 phosphotransferase Human genes 0.000 description 6
239000000843 powder Substances 0.000 description 6
238000002953 preparative HPLC Methods 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
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 5
NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 5
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 5
125000004122 cyclic group Chemical group 0.000 description 5
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
239000000706 filtrate Substances 0.000 description 5
229910052943 magnesium sulfate Inorganic materials 0.000 description 5
229910052757 nitrogen Inorganic materials 0.000 description 5
125000004043 oxo group Chemical group O=* 0.000 description 5
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 5
238000002360 preparation method Methods 0.000 description 5
239000000725 suspension Substances 0.000 description 5
101150041968 CDC13 gene Proteins 0.000 description 4
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