CS247168B2

CS247168B2 - Method of new carbapenem derivatives production

Method of new carbapenem derivatives production Download PDF

Info

Publication number: CS247168B2
Authority: CS; Czechoslovakia
Prior art keywords: carbon atoms; alkyl; formula; group; ring
Prior art date: 1982-09-28

Application number

CS837049A

Other languages

Czech (cs)

English (en)

Inventor

Un Kim Choung

Original Assignee

Bristol Myers Co

Priority date

1982-09-28

Filing date

1983-09-27

Publication date

1986-12-18

1983-09-27 Application filed by Bristol Myers Co filed Critical Bristol Myers Co

1985-03-13 Priority to CS851754A priority Critical patent/CS247195B2/cs

1986-12-18 Publication of CS247168B2 publication Critical patent/CS247168B2/cs

Links

YZBQHRLRFGPBSL-RXMQYKEDSA-N carbapenem Chemical class C1C=CN2C(=O)C[C@H]21 YZBQHRLRFGPBSL-RXMQYKEDSA-N 0.000 title claims abstract description 46
238000000034 method Methods 0.000 title claims description 49
238000004519 manufacturing process Methods 0.000 title claims description 3
125000004432 carbon atom Chemical group C* 0.000 claims abstract description 228
-1 araliphatic Chemical group 0.000 claims abstract description 172
125000001424 substituent group Chemical group 0.000 claims abstract description 112
229910052799 carbon Inorganic materials 0.000 claims abstract description 80
125000000623 heterocyclic group Chemical group 0.000 claims abstract description 68
125000001072 heteroaryl group Chemical group 0.000 claims abstract description 56
125000003118 aryl group Chemical group 0.000 claims abstract description 42
125000001931 aliphatic group Chemical group 0.000 claims abstract description 16
125000002947 alkylene group Chemical group 0.000 claims abstract description 13
125000000217 alkyl group Chemical group 0.000 claims description 202
150000001875 compounds Chemical class 0.000 claims description 196
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 152
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 120
229910052757 nitrogen Inorganic materials 0.000 claims description 112
229910052739 hydrogen Inorganic materials 0.000 claims description 96
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 77
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 74
239000000460 chlorine Substances 0.000 claims description 60
239000001257 hydrogen Substances 0.000 claims description 58
229910052801 chlorine Inorganic materials 0.000 claims description 56
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 54
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 52
125000005842 heteroatom Chemical group 0.000 claims description 52
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 52
229910052794 bromium Inorganic materials 0.000 claims description 51
229910052731 fluorine Inorganic materials 0.000 claims description 51
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 50
239000011737 fluorine Substances 0.000 claims description 50
239000002904 solvent Substances 0.000 claims description 49
229910052717 sulfur Inorganic materials 0.000 claims description 45
125000004446 heteroarylalkyl group Chemical group 0.000 claims description 44
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 43
229910052760 oxygen Inorganic materials 0.000 claims description 40
238000002360 preparation method Methods 0.000 claims description 40
125000006239 protecting group Chemical group 0.000 claims description 39
FYZUENZXIZCLAZ-UHFFFAOYSA-N 2-methylhept-2-enoic acid Chemical compound CCCCC=C(C)C(O)=O FYZUENZXIZCLAZ-UHFFFAOYSA-N 0.000 claims description 38
239000001301 oxygen Substances 0.000 claims description 38
229910052736 halogen Inorganic materials 0.000 claims description 36
150000002367 halogens Chemical group 0.000 claims description 36
125000000753 cycloalkyl group Chemical group 0.000 claims description 34
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 33
150000003839 salts Chemical class 0.000 claims description 33
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 31
125000004433 nitrogen atom Chemical group N* 0.000 claims description 28
125000003710 aryl alkyl group Chemical group 0.000 claims description 25
125000003342 alkenyl group Chemical group 0.000 claims description 24
125000004434 sulfur atom Chemical group 0.000 claims description 23
150000001450 anions Chemical class 0.000 claims description 22
125000000304 alkynyl group Chemical group 0.000 claims description 20
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 19
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 18
125000004429 atom Chemical group 0.000 claims description 18
125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 18
239000011593 sulfur Substances 0.000 claims description 18
125000003545 alkoxy group Chemical group 0.000 claims description 16
239000003960 organic solvent Substances 0.000 claims description 16
229920006395 saturated elastomer Polymers 0.000 claims description 16
125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 15
125000006503 p-nitrobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1[N+]([O-])=O)C([H])([H])* 0.000 claims description 15
230000008569 process Effects 0.000 claims description 15
125000005018 aryl alkenyl group Chemical group 0.000 claims description 14
PIGFYZPCRLYGLF-UHFFFAOYSA-N Aluminum nitride Chemical compound [Al]#N PIGFYZPCRLYGLF-UHFFFAOYSA-N 0.000 claims description 12
150000002500 ions Chemical class 0.000 claims description 12
125000003367 polycyclic group Chemical group 0.000 claims description 11
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 10
125000004093 cyano group Chemical group *C#N 0.000 claims description 10
150000003254 radicals Chemical class 0.000 claims description 10
239000007858 starting material Substances 0.000 claims description 10
239000002168 alkylating agent Substances 0.000 claims description 8
229940100198 alkylating agent Drugs 0.000 claims description 8
125000000129 anionic group Chemical group 0.000 claims description 8
125000001246 bromo group Chemical group Br* 0.000 claims description 8
125000001153 fluoro group Chemical group F* 0.000 claims description 8
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 7
125000005119 alkyl cycloalkyl group Chemical group 0.000 claims description 7
125000004414 alkyl thio group Chemical group 0.000 claims description 7
125000001309 chloro group Chemical group Cl* 0.000 claims description 7
ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical group C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 claims description 7
125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 7
238000005956 quaternization reaction Methods 0.000 claims description 7
125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 claims description 6
125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 6
125000002950 monocyclic group Chemical group 0.000 claims description 6
125000005633 phthalidyl group Chemical group 0.000 claims description 6
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 5
DGYIJVNZSDYBOE-UHFFFAOYSA-N [CH2]C1=CC=NC=C1 Chemical group [CH2]C1=CC=NC=C1 DGYIJVNZSDYBOE-UHFFFAOYSA-N 0.000 claims description 5
125000001539 acetonyl group Chemical group [H]C([H])([H])C(=O)C([H])([H])* 0.000 claims description 5
125000001118 alkylidene group Chemical group 0.000 claims description 5
125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 5
239000003153 chemical reaction reagent Substances 0.000 claims description 5
125000006000 trichloroethyl group Chemical group 0.000 claims description 5
LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 claims description 4
XAKBSHICSHRJCL-UHFFFAOYSA-N [CH2]C(=O)C1=CC=CC=C1 Chemical group [CH2]C(=O)C1=CC=CC=C1 XAKBSHICSHRJCL-UHFFFAOYSA-N 0.000 claims description 4
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 4
SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims description 4
125000004954 trialkylamino group Chemical group 0.000 claims description 4
125000004665 trialkylsilyl group Chemical group 0.000 claims description 4
239000004927 clay Substances 0.000 claims description 2
PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical class [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 claims 2
BHMLFPOTZYRDKA-IRXDYDNUSA-N (2s)-2-[(s)-(2-iodophenoxy)-phenylmethyl]morpholine Chemical compound IC1=CC=CC=C1O[C@@H](C=1C=CC=CC=1)[C@H]1OCCNC1 BHMLFPOTZYRDKA-IRXDYDNUSA-N 0.000 claims 1
230000002152 alkylating effect Effects 0.000 claims 1
125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims 1
MDQRDWAGHRLBPA-UHFFFAOYSA-N fluoroamine Chemical group FN MDQRDWAGHRLBPA-UHFFFAOYSA-N 0.000 claims 1
125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 claims 1
239000004179 indigotine Substances 0.000 claims 1
125000004354 sulfur functional group Chemical group 0.000 claims 1
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 1
239000003242 anti bacterial agent Substances 0.000 abstract description 6
230000003389 potentiating effect Effects 0.000 abstract description 3
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 278
239000000243 solution Substances 0.000 description 229
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 216
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 183
239000000203 mixture Substances 0.000 description 119
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 96
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 96
238000005481 NMR spectroscopy Methods 0.000 description 90
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 86
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 86
239000007787 solid Substances 0.000 description 84
239000011541 reaction mixture Substances 0.000 description 79
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 76
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 57
239000000543 intermediate Substances 0.000 description 54
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 52
YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 45
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 43
239000003921 oil Substances 0.000 description 43
235000019198 oils Nutrition 0.000 description 43
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 42
239000000843 powder Substances 0.000 description 39
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 38
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 37
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 33
238000006243 chemical reaction Methods 0.000 description 31
239000012071 phase Substances 0.000 description 29
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 28
239000002244 precipitate Substances 0.000 description 28
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 27
239000000706 filtrate Substances 0.000 description 27
239000000047 product Substances 0.000 description 26
238000004458 analytical method Methods 0.000 description 25
239000008363 phosphate buffer Substances 0.000 description 25
241000588724 Escherichia coli Species 0.000 description 24
230000002441 reversible effect Effects 0.000 description 24
150000003573 thiols Chemical class 0.000 description 24
150000002431 hydrogen Chemical class 0.000 description 23
239000012299 nitrogen atmosphere Substances 0.000 description 23
125000003282 alkyl amino group Chemical group 0.000 description 22
ZSKVGTPCRGIANV-ZXFLCMHBSA-N imipenem Chemical compound C1C(SCC\N=C\N)=C(C(O)=O)N2C(=O)[C@H]([C@H](O)C)[C@H]21 ZSKVGTPCRGIANV-ZXFLCMHBSA-N 0.000 description 22
239000000725 suspension Substances 0.000 description 22
BHIIGRBMZRSDRI-UHFFFAOYSA-N [chloro(phenoxy)phosphoryl]oxybenzene Chemical compound C=1C=CC=CC=1OP(=O)(Cl)OC1=CC=CC=C1 BHIIGRBMZRSDRI-UHFFFAOYSA-N 0.000 description 21
239000003054 catalyst Substances 0.000 description 21
238000001704 evaporation Methods 0.000 description 21
125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 description 21
125000004663 dialkyl amino group Chemical group 0.000 description 20
230000008020 evaporation Effects 0.000 description 20
238000004128 high performance liquid chromatography Methods 0.000 description 20
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 20
239000003643 water by type Substances 0.000 description 20
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 19
239000002253 acid Substances 0.000 description 19
239000012267 brine Substances 0.000 description 19
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 18
239000000741 silica gel Substances 0.000 description 17
229910002027 silica gel Inorganic materials 0.000 description 17
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 16
241000699670 Mus sp. Species 0.000 description 16
238000004108 freeze drying Methods 0.000 description 16
PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 16
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 16
125000000229 (C1-C4)alkoxy group Chemical group 0.000 description 15
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 15
239000000872 buffer Substances 0.000 description 15
150000001721 carbon Chemical group 0.000 description 15
150000002148 esters Chemical group 0.000 description 14
229910052943 magnesium sulfate Inorganic materials 0.000 description 14
235000019341 magnesium sulphate Nutrition 0.000 description 14
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 14
238000010521 absorption reaction Methods 0.000 description 13
QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 13
239000008346 aqueous phase Substances 0.000 description 13
238000000746 purification Methods 0.000 description 13
238000003756 stirring Methods 0.000 description 13
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 12
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 12
241000588697 Enterobacter cloacae Species 0.000 description 12
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 12
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
125000005843 halogen group Chemical group 0.000 description 12
239000000463 material Substances 0.000 description 12
239000012074 organic phase Substances 0.000 description 12
UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 12
LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 12
244000038458 Nepenthes mirabilis Species 0.000 description 11
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 11
WKDDRNSBRWANNC-ATRFCDNQSA-N Thienamycin Chemical compound C1C(SCCN)=C(C(O)=O)N2C(=O)[C@H]([C@H](O)C)[C@H]21 WKDDRNSBRWANNC-ATRFCDNQSA-N 0.000 description 11
229910052740 iodine Inorganic materials 0.000 description 11
JUJWROOIHBZHMG-UHFFFAOYSA-O pyridinium Chemical compound C1=CC=[NH+]C=C1 JUJWROOIHBZHMG-UHFFFAOYSA-O 0.000 description 11
238000005406 washing Methods 0.000 description 11
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 10
WKDDRNSBRWANNC-UHFFFAOYSA-N Thienamycin Natural products C1C(SCCN)=C(C(O)=O)N2C(=O)C(C(O)C)C21 WKDDRNSBRWANNC-UHFFFAOYSA-N 0.000 description 10
125000002252 acyl group Chemical group 0.000 description 10
125000003277 amino group Chemical group 0.000 description 10
125000004178 (C1-C4) alkyl group Chemical group 0.000 description 9
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 9
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
229910019142 PO4 Inorganic materials 0.000 description 9
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 9
125000004423 acyloxy group Chemical group 0.000 description 9
230000000694 effects Effects 0.000 description 9
239000003480 eluent Substances 0.000 description 9
238000010828 elution Methods 0.000 description 9
238000007918 intramuscular administration Methods 0.000 description 9
239000011630 iodine Chemical group 0.000 description 9
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 9
OIRDBPQYVWXNSJ-UHFFFAOYSA-N methyl trifluoromethansulfonate Chemical compound COS(=O)(=O)C(F)(F)F OIRDBPQYVWXNSJ-UHFFFAOYSA-N 0.000 description 9
238000010992 reflux Methods 0.000 description 9
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
238000004587 chromatography analysis Methods 0.000 description 8
239000013078 crystal Substances 0.000 description 8
239000010452 phosphate Substances 0.000 description 8
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 8
210000002966 serum Anatomy 0.000 description 8
239000011734 sodium Substances 0.000 description 8
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 7
241000238876 Acari Species 0.000 description 7
244000110797 Polygonum persicaria Species 0.000 description 7
241000588777 Providencia rettgeri Species 0.000 description 7
239000007864 aqueous solution Substances 0.000 description 7
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 7
125000002837 carbocyclic group Chemical group 0.000 description 7
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 7
239000006260 foam Substances 0.000 description 7
238000005984 hydrogenation reaction Methods 0.000 description 7
150000002576 ketones Chemical class 0.000 description 7
125000003884 phenylalkyl group Chemical group 0.000 description 7
239000000126 substance Substances 0.000 description 7
239000011701 zinc Substances 0.000 description 7
238000005160 1H NMR spectroscopy Methods 0.000 description 6
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
241000421809 Brisaster fragilis Species 0.000 description 6
GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 description 6
241000588772 Morganella morganii Species 0.000 description 6
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 6
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 6
XXROGKLTLUQVRX-UHFFFAOYSA-N allyl alcohol Chemical compound OCC=C XXROGKLTLUQVRX-UHFFFAOYSA-N 0.000 description 6
229940041011 carbapenems Drugs 0.000 description 6
150000007942 carboxylates Chemical class 0.000 description 6
239000013058 crude material Substances 0.000 description 6
125000004122 cyclic group Chemical group 0.000 description 6
238000004821 distillation Methods 0.000 description 6
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
238000001727 in vivo Methods 0.000 description 6
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
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