TW200418813A

TW200418813A - Novel compounds

Novel compounds Download PDF

Info

Publication number: TW200418813A
Authority: TW; Taiwan
Prior art keywords: methyl; phenyl; alkyl; compound; amino
Prior art date: 2002-11-07

Application number

TW092130829A

Other languages

English (en)

Chinese (zh)

Inventor

William Brown

Andrew Griffin

Original Assignee

Astrazeneca Ab

Priority date

2002-11-07

Filing date

2003-11-04

Publication date

2004-10-01

2003-11-04 Application filed by Astrazeneca Ab filed Critical Astrazeneca Ab

2004-10-01 Publication of TW200418813A publication Critical patent/TW200418813A/zh

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150000001875 compounds Chemical class 0.000 title claims abstract description 160
208000002193 Pain Diseases 0.000 claims abstract description 19
150000003839 salts Chemical class 0.000 claims abstract description 17
230000036407 pain Effects 0.000 claims abstract description 14
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims abstract description 13
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 9
238000002560 therapeutic procedure Methods 0.000 claims abstract description 4
-1 p-pyridyl Chemical group 0.000 claims description 206
238000006243 chemical reaction Methods 0.000 claims description 171
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 168
229910052757 nitrogen Inorganic materials 0.000 claims description 159
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 150
125000000217 alkyl group Chemical group 0.000 claims description 147
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 99
238000000034 method Methods 0.000 claims description 42
229910052736 halogen Inorganic materials 0.000 claims description 37
ZMANZCXQSJIPKH-UHFFFAOYSA-N N,N-Diethylethanamine Substances CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 36
125000003118 aryl group Chemical group 0.000 claims description 36
CYSPWCARDHRYJX-UHFFFAOYSA-N 9h-fluoren-1-amine Chemical compound C12=CC=CC=C2CC2=C1C=CC=C2N CYSPWCARDHRYJX-UHFFFAOYSA-N 0.000 claims description 34
150000002367 halogens Chemical class 0.000 claims description 34
150000001412 amines Chemical class 0.000 claims description 33
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 30
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 30
125000001072 heteroaryl group Chemical group 0.000 claims description 28
RTZKZFJDLAIYFH-UHFFFAOYSA-N diethyl ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 26
125000003545 alkoxy group Chemical group 0.000 claims description 24
125000000753 cycloalkyl group Chemical group 0.000 claims description 23
238000011282 treatment Methods 0.000 claims description 21
239000003814 drug Substances 0.000 claims description 17
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 16
125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 claims description 15
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 15
241001465754 Metazoa Species 0.000 claims description 14
125000004076 pyridyl group Chemical group 0.000 claims description 14
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 13
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 12
239000000126 substance Substances 0.000 claims description 12
150000003254 radicals Chemical class 0.000 claims description 11
208000019901 Anxiety disease Diseases 0.000 claims description 9
229910052739 hydrogen Inorganic materials 0.000 claims description 9
125000000168 pyrrolyl group Chemical group 0.000 claims description 9
125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 8
WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 claims description 8
125000002541 furyl group Chemical group 0.000 claims description 8
125000006308 propyl amino group Chemical group 0.000 claims description 8
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 7
125000000304 alkynyl group Chemical group 0.000 claims description 7
230000036506 anxiety Effects 0.000 claims description 7
125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 7
125000002883 imidazolyl group Chemical group 0.000 claims description 7
125000003386 piperidinyl group Chemical group 0.000 claims description 7
125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 6
208000018522 Gastrointestinal disease Diseases 0.000 claims description 6
239000003937 drug carrier Substances 0.000 claims description 6
125000003226 pyrazolyl group Chemical group 0.000 claims description 6
238000007347 radical substitution reaction Methods 0.000 claims description 6
125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 5
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 5
125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 5
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 5
QUSNBJAOOMFDIB-UHFFFAOYSA-N monoethyl amine Natural products CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 claims description 5
238000006467 substitution reaction Methods 0.000 claims description 5
125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 4
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 4
150000001335 aliphatic alkanes Chemical group 0.000 claims description 4
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 4
125000006639 cyclohexyl carbonyl group Chemical group 0.000 claims description 4
125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 4
238000010586 diagram Methods 0.000 claims description 4
125000004914 dipropylamino group Chemical group C(CC)N(CCC)* 0.000 claims description 4
125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 4
239000001301 oxygen Substances 0.000 claims description 4
229910052760 oxygen Inorganic materials 0.000 claims description 4
125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 4
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 4
125000001425 triazolyl group Chemical group 0.000 claims description 4
241000283074 Equus asinus Species 0.000 claims description 3
241001529936 Murinae Species 0.000 claims description 3
HFACYLZERDEVSX-UHFFFAOYSA-N benzidine Chemical compound C1=CC(N)=CC=C1C1=CC=C(N)C=C1 HFACYLZERDEVSX-UHFFFAOYSA-N 0.000 claims description 3
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
229910052802 copper Inorganic materials 0.000 claims description 3
125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 3
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
125000001844 prenyl group Chemical group [H]C([*])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims description 3
125000003944 tolyl group Chemical group 0.000 claims description 3
125000004080 3-carboxypropanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C(O[H])=O 0.000 claims description 2
VUTBELPREDJDDH-UHFFFAOYSA-N 4-amino-5-hydroxymethyl-2-methylpyrimidine Chemical compound CC1=NC=C(CO)C(N)=N1 VUTBELPREDJDDH-UHFFFAOYSA-N 0.000 claims description 2
ABZPQPREPTZBMO-UHFFFAOYSA-N 9h-fluorene-1-carboxamide Chemical compound C1C2=CC=CC=C2C2=C1C(C(=O)N)=CC=C2 ABZPQPREPTZBMO-UHFFFAOYSA-N 0.000 claims description 2
239000008280 blood Substances 0.000 claims description 2
210000004369 blood Anatomy 0.000 claims description 2
239000003638 chemical reducing agent Substances 0.000 claims description 2
125000006547 cyclononyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
125000006312 cyclopentyl amino group Chemical group [H]N(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 claims description 2
150000004820 halides Chemical class 0.000 claims description 2
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
125000002971 oxazolyl group Chemical group 0.000 claims description 2
125000005936 piperidyl group Chemical group 0.000 claims description 2
MXXWOMGUGJBKIW-YPCIICBESA-N piperine Chemical compound C=1C=C2OCOC2=CC=1/C=C/C=C/C(=O)N1CCCCC1 MXXWOMGUGJBKIW-YPCIICBESA-N 0.000 claims description 2
WVWHRXVVAYXKDE-UHFFFAOYSA-N piperine Natural products O=C(C=CC=Cc1ccc2OCOc2c1)C3CCCCN3 WVWHRXVVAYXKDE-UHFFFAOYSA-N 0.000 claims description 2
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
125000005843 halogen group Chemical group 0.000 claims 5
125000002653 sulfanylmethyl group Chemical group [H]SC([H])([H])[*] 0.000 claims 2
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 1
YJTKZCDBKVTVBY-UHFFFAOYSA-N 1,3-Diphenylbenzene Chemical group C1=CC=CC=C1C1=CC=CC(C=2C=CC=CC=2)=C1 YJTKZCDBKVTVBY-UHFFFAOYSA-N 0.000 claims 1
BMVXCPBXGZKUPN-UHFFFAOYSA-N 1-hexanamine Chemical compound CCCCCCN BMVXCPBXGZKUPN-UHFFFAOYSA-N 0.000 claims 1
VEDTXTNSFWUXGQ-UHFFFAOYSA-N Carbophenothion Chemical group CCOP(=S)(OCC)SCSC1=CC=C(Cl)C=C1 VEDTXTNSFWUXGQ-UHFFFAOYSA-N 0.000 claims 1
XZMCDFZZKTWFGF-UHFFFAOYSA-N Cyanamide Chemical compound NC#N XZMCDFZZKTWFGF-UHFFFAOYSA-N 0.000 claims 1
208000014540 Functional gastrointestinal disease Diseases 0.000 claims 1
VQTUBCCKSQIDNK-UHFFFAOYSA-N Isobutene Chemical group CC(C)=C VQTUBCCKSQIDNK-UHFFFAOYSA-N 0.000 claims 1
229920000877 Melamine resin Polymers 0.000 claims 1
235000015429 Mirabilis expansa Nutrition 0.000 claims 1
244000294411 Mirabilis expansa Species 0.000 claims 1
229910006069 SO3H Inorganic materials 0.000 claims 1
241000270666 Testudines Species 0.000 claims 1
125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims 1
125000003710 aryl alkyl group Chemical group 0.000 claims 1
125000004356 hydroxy functional group Chemical group O* 0.000 claims 1
125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 claims 1
JDSHMPZPIAZGSV-UHFFFAOYSA-N melamine Chemical compound NC1=NC(N)=NC(N)=N1 JDSHMPZPIAZGSV-UHFFFAOYSA-N 0.000 claims 1
WDWDWGRYHDPSDS-UHFFFAOYSA-N methanimine Chemical compound N=C WDWDWGRYHDPSDS-UHFFFAOYSA-N 0.000 claims 1
235000013536 miso Nutrition 0.000 claims 1
ZWRDBWDXRLPESY-UHFFFAOYSA-N n-benzyl-n-ethylethanamine Chemical compound CCN(CC)CC1=CC=CC=C1 ZWRDBWDXRLPESY-UHFFFAOYSA-N 0.000 claims 1
HVAAHUDGWQAAOJ-UHFFFAOYSA-N n-benzylethanamine Chemical compound CCNCC1=CC=CC=C1 HVAAHUDGWQAAOJ-UHFFFAOYSA-N 0.000 claims 1
125000001151 peptidyl group Chemical group 0.000 claims 1
230000000144 pharmacologic effect Effects 0.000 claims 1
125000005289 uranyl group Chemical group 0.000 claims 1
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 463
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 297
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 178
239000000243 solution Substances 0.000 description 125
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 122
239000000543 intermediate Substances 0.000 description 112
238000004128 high performance liquid chromatography Methods 0.000 description 110
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 107
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 102
239000000047 product Substances 0.000 description 85
OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 80
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 77
230000003287 optical effect Effects 0.000 description 77
239000007787 solid Substances 0.000 description 70
229910001868 water Inorganic materials 0.000 description 66
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 61
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 59
229920006395 saturated elastomer Polymers 0.000 description 57
239000010410 layer Substances 0.000 description 54
229910052763 palladium Inorganic materials 0.000 description 51
229910000030 sodium bicarbonate Inorganic materials 0.000 description 49
235000017557 sodium bicarbonate Nutrition 0.000 description 49
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 47
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 41
239000000284 extract Substances 0.000 description 39
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 38
238000004366 reverse phase liquid chromatography Methods 0.000 description 38
DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 37
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 30
VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 30
238000012360 testing method Methods 0.000 description 29
239000012074 organic phase Substances 0.000 description 28
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 27
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 26
125000000623 heterocyclic group Chemical group 0.000 description 25
239000000203 mixture Substances 0.000 description 24
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 21
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 20
239000002904 solvent Substances 0.000 description 20
229910000831 Steel Inorganic materials 0.000 description 18
239000010959 steel Substances 0.000 description 18
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 17
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 16
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
238000004458 analytical method Methods 0.000 description 15
239000012043 crude product Substances 0.000 description 15
JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 15
239000011541 reaction mixture Substances 0.000 description 15
239000002585 base Substances 0.000 description 14
235000019439 ethyl acetate Nutrition 0.000 description 14
125000001183 hydrocarbyl group Chemical group 0.000 description 14
239000012321 sodium triacetoxyborohydride Substances 0.000 description 14
241000282414 Homo sapiens Species 0.000 description 13
239000007788 liquid Substances 0.000 description 13
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 12
241000699666 Mus <mouse, genus> Species 0.000 description 12
229940079593 drug Drugs 0.000 description 12
229940126657 Compound 17 Drugs 0.000 description 11
101100244562 Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1) oprD gene Proteins 0.000 description 11
238000004440 column chromatography Methods 0.000 description 11
108700023159 delta Opioid Receptors Proteins 0.000 description 11
102000048124 delta Opioid Receptors Human genes 0.000 description 11
239000002158 endotoxin Substances 0.000 description 11
239000006260 foam Substances 0.000 description 11
239000000463 material Substances 0.000 description 11
AOSZTAHDEDLTLQ-AZKQZHLXSA-N (1S,2S,4R,8S,9S,11S,12R,13S,19S)-6-[(3-chlorophenyl)methyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one Chemical compound C([C@@H]1C[C@H]2[C@H]3[C@]([C@]4(C=CC(=O)C=C4[C@@H](F)C3)C)(F)[C@@H](O)C[C@@]2([C@@]1(C1)C(=O)CO)C)N1CC1=CC=CC(Cl)=C1 AOSZTAHDEDLTLQ-AZKQZHLXSA-N 0.000 description 10
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 10
235000011114 ammonium hydroxide Nutrition 0.000 description 10
239000007864 aqueous solution Substances 0.000 description 10
229920006008 lipopolysaccharide Polymers 0.000 description 10
239000012071 phase Substances 0.000 description 10
239000000741 silica gel Substances 0.000 description 10
229910002027 silica gel Inorganic materials 0.000 description 10
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 9
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical compound C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 9
125000004432 carbon atom Chemical group C* 0.000 description 9
238000003818 flash chromatography Methods 0.000 description 9
238000003756 stirring Methods 0.000 description 9
CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 8
239000002253 acid Substances 0.000 description 8
JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 8
229910052742 iron Inorganic materials 0.000 description 8
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