JPH0133104B2 - - Google Patents
Info
- Publication number
- JPH0133104B2 JPH0133104B2 JP57132922A JP13292282A JPH0133104B2 JP H0133104 B2 JPH0133104 B2 JP H0133104B2 JP 57132922 A JP57132922 A JP 57132922A JP 13292282 A JP13292282 A JP 13292282A JP H0133104 B2 JPH0133104 B2 JP H0133104B2
- Authority
- JP
- Japan
- Prior art keywords
- formula
- methyl
- reaction
- pyridyl
- alkyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
- 238000000034 method Methods 0.000 claims description 48
- 239000008096 xylene Substances 0.000 claims description 30
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 24
- 238000006243 chemical reaction Methods 0.000 claims description 23
- -1 2-thiazolyl Chemical group 0.000 claims description 19
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 14
- 125000000217 alkyl group Chemical group 0.000 claims description 11
- 239000012452 mother liquor Substances 0.000 claims description 11
- 150000001412 amines Chemical class 0.000 claims description 10
- 239000003960 organic solvent Substances 0.000 claims description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
- 125000004432 carbon atom Chemical group C* 0.000 claims description 8
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 238000010438 heat treatment Methods 0.000 claims description 2
- HZILLNCYNQANBR-UHFFFAOYSA-N 1,1-dioxo-3,4-dihydro-2h-1$l^{6},2-benzothiazine-3-carboxamide Chemical compound C1=CC=C2S(=O)(=O)NC(C(=O)N)CC2=C1 HZILLNCYNQANBR-UHFFFAOYSA-N 0.000 claims 1
- 239000000047 product Substances 0.000 description 31
- 150000001875 compounds Chemical class 0.000 description 21
- 239000000543 intermediate Substances 0.000 description 20
- ICSNLGPSRYBMBD-UHFFFAOYSA-N 2-aminopyridine Chemical compound NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 0.000 description 16
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 15
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- 239000000203 mixture Substances 0.000 description 14
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 13
- QYSPLQLAKJAUJT-UHFFFAOYSA-N piroxicam Chemical compound OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC1=CC=CC=N1 QYSPLQLAKJAUJT-UHFFFAOYSA-N 0.000 description 11
- 239000002904 solvent Substances 0.000 description 11
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 239000013078 crystal Substances 0.000 description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 9
- 229960002702 piroxicam Drugs 0.000 description 9
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 8
- 238000010992 reflux Methods 0.000 description 8
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- YNQLUTRBYVCPMQ-UHFFFAOYSA-N Ethylbenzene Chemical compound CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- 229940121363 anti-inflammatory agent Drugs 0.000 description 6
- 239000002260 anti-inflammatory agent Substances 0.000 description 6
- NNBZCPXTIHJBJL-UHFFFAOYSA-N decalin Chemical compound C1CCCC2CCCCC21 NNBZCPXTIHJBJL-UHFFFAOYSA-N 0.000 description 6
- 239000007858 starting material Substances 0.000 description 6
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 6
- 150000003738 xylenes Chemical class 0.000 description 6
- 229910052799 carbon Inorganic materials 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- 238000002844 melting Methods 0.000 description 5
- 230000008018 melting Effects 0.000 description 5
- 229910052757 nitrogen Inorganic materials 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- 238000010561 standard procedure Methods 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 4
- 238000005481 NMR spectroscopy Methods 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 238000004821 distillation Methods 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 239000012299 nitrogen atmosphere Substances 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 239000000376 reactant Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 238000007792 addition Methods 0.000 description 3
- 230000000052 comparative effect Effects 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 125000000623 heterocyclic group Chemical group 0.000 description 3
- 238000002955 isolation Methods 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 238000012545 processing Methods 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- PXXNTAGJWPJAGM-UHFFFAOYSA-N vertaline Natural products C1C2C=3C=C(OC)C(OC)=CC=3OC(C=C3)=CC=C3CCC(=O)OC1CC1N2CCCC1 PXXNTAGJWPJAGM-UHFFFAOYSA-N 0.000 description 3
- PAAZPARNPHGIKF-UHFFFAOYSA-N 1,2-dibromoethane Chemical compound BrCCBr PAAZPARNPHGIKF-UHFFFAOYSA-N 0.000 description 2
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 2
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 2
- SYCHUQUJURZQMO-UHFFFAOYSA-N 4-hydroxy-2-methyl-1,1-dioxo-n-(1,3-thiazol-2-yl)-1$l^{6},2-benzothiazine-3-carboxamide Chemical class OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC1=NC=CS1 SYCHUQUJURZQMO-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N Methyl ethyl ketone Natural products CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 2
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000002329 infrared spectrum Methods 0.000 description 2
- 125000004430 oxygen atom Chemical group O* 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 239000002002 slurry Substances 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 125000000335 thiazolyl group Chemical group 0.000 description 2
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- RAIPHJJURHTUIC-UHFFFAOYSA-N 1,3-thiazol-2-amine Chemical compound NC1=NC=CS1 RAIPHJJURHTUIC-UHFFFAOYSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- FIPBGFYKXKDTFW-UHFFFAOYSA-N 2-methyl-4-oxo-3h-1,2-benzothiazine-3-carboxylic acid Chemical compound C1=CC=C2C(=O)C(C(O)=O)N(C)SC2=C1 FIPBGFYKXKDTFW-UHFFFAOYSA-N 0.000 description 1
- UJVBZCCNLAAMOV-UHFFFAOYSA-N 2h-1,2-benzothiazine Chemical compound C1=CC=C2C=CNSC2=C1 UJVBZCCNLAAMOV-UHFFFAOYSA-N 0.000 description 1
- FKOSZDBJQBJDIV-UHFFFAOYSA-N 2h-1,2-benzothiazine-3-carboxamide Chemical compound C1=CC=C2SNC(C(=O)N)=CC2=C1 FKOSZDBJQBJDIV-UHFFFAOYSA-N 0.000 description 1
- YBRHODCMROOROS-UHFFFAOYSA-N 2h-1,2-benzothiazine-3-carboxylic acid Chemical compound C1=CC=C2SNC(C(=O)O)=CC2=C1 YBRHODCMROOROS-UHFFFAOYSA-N 0.000 description 1
- QRAOZQGIUIDZQZ-UHFFFAOYSA-N 4-methyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1,4-benzoxazine Chemical compound C=1C=C2N(C)CCOC2=CC=1B1OC(C)(C)C(C)(C)O1 QRAOZQGIUIDZQZ-UHFFFAOYSA-N 0.000 description 1
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical class NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 1
- 238000002441 X-ray diffraction Methods 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 150000001721 carbon Chemical class 0.000 description 1
- 150000003857 carboxamides Chemical class 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000000113 differential scanning calorimetry Methods 0.000 description 1
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 239000012948 isocyanate Substances 0.000 description 1
- 150000002513 isocyanates Chemical class 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- GIQCXAYKJYPPFK-UHFFFAOYSA-N methyl 2-methyl-1,1,4-trioxo-3h-1$l^{6},2-benzothiazine-3-carboxylate Chemical compound C1=CC=C2C(=O)C(C(=O)OC)N(C)S(=O)(=O)C2=C1 GIQCXAYKJYPPFK-UHFFFAOYSA-N 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 238000003801 milling Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 230000003134 recirculating effect Effects 0.000 description 1
- 238000004064 recycling Methods 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 229950005175 sudoxicam Drugs 0.000 description 1
- 150000003457 sulfones Chemical class 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 238000005891 transamination reaction Methods 0.000 description 1
- 150000005671 trienes Chemical class 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Description
ãçºæã®è©³çŽ°ãªèª¬æã
æ¬çºæã¯ããã³ãŸãã¢ãžã³ã«ã«ãããµããæç
çå€ã®æ¹è¯ããã補é æ³ã«é¢ããã â眮æããããã³ãŸãã¢ãžã³ã«ã«ãããµãã
æççå€åæã®ããã®äºã€ã®æ¹æ³ããç±³åœç¹èš±ç¬¬
3591584å·ã«ç€ºãããŠããããããã®ãã¡ã®ç¬¬äž
ã®ãã®ã¯ãâ眮æåºãè€çŽ ç°æåã§ãªãã«ã«ã
ããµããã補é ããããã«çšãããããããã¯ã
ææ©ã€ãœã·ã¢ããŒããR3NCOïŒåŒäžR3ã¯äŸãã°
äžå®ã®ã¢ã«ãã«åºãããšãã«åºãŸãã¯ãããã«åº
ã§ããïŒããïŒâãªããœïŒãŸãã¯ïŒâãªããœïŒ
ïŒïŒïŒâãã³ãŸãã¢ãžã³ãšæ¥è§ŠãããŠãäŸãã°åŒ ã®ååç©ãŸãã¯çžåœããïŒâãªããœâïŒâã«ã«ã
ããµãããçæãããããšã«ããæãã 第äºã®æ¹æ³ã¯ãâ眮æåºãè€çŽ ç°æåã§ã
ãããããã®ã¢ããã®è£œé ã«å¥œé©ã§ããïŒãã®æ¹
æ³ã¯ãææã®ãã³ãŸãã¢ãžã³ã«ã«ãããµãããç
æããããã®ãçžåœããã«ã«ãã³é žãšã¹ãã«ãšé©
åœãªã¢ãã³ãR2NH2ïŒR2ã¯è€çŽ ç°åºã§ããïŒãšã®
åå¿ã äŸãã°ã ãå å«ããã ç±³åœç¹èš±ç¬¬3891637å·ã«ã¯ãã¢ããåºè»¢ç§»å·¥çš
ã«ãã€ãŠãåŒïŒïŒã®ïŒ®âè€çŽ ç°ã¢ãããçžåœã
ãâããšãã«ã¢ããããåŸãæ¹æ³ã瀺ãããŠã
ãã ç±³åœç¹èš±ç¬¬3853862å·ã«ã¯ãéå±æ°ŽçŽ åç©ã®å
åšã«ããããã³ãŒã³ã¹ã«ããã«ã°ãªã·ã³ã¢ãã
ïŒïŒã®ç°åã«ãããåŒïŒïŒã®ïŒâãªããœâïŒïŒ
ïŒâãã³ãŸãã¢ãžã³âïŒâã«ã«ãããµããã®è£œé
æ¹æ³ãäŸãã° ã瀺ãããŠããã 1981幎ïŒæ15æ¥çºè¡ã®ç±³åœç¹èš±ç¬¬4289879å·ã«
ã¯ãçžåœããïŒâïŒïŒâã¡ããã·ãšãã«ïŒãšã¹ã
ã«ãçµç±ãããããã¯ã·ã«ã ïŒpiroxicamïŒãïŒ
âããããã·âïŒâã¡ãã«ââïŒïŒâããªãžã«ïŒ
â2HâïŒïŒïŒâãã³ãŸãã¢ãžã³âïŒâã«ã«ãã
ãµããïŒïŒïŒâãžãªãã·ããã®è£œæ³ãèšèŒãããŠ
ããã æ¬çºæã¯æ¬¡åŒã®ïŒïŒïŒâãžãããâ2HâïŒïŒ
ïŒâãã³ãŸãã¢ãžã³âïŒâã«ã«ãããµããâïŒïŒ
ïŒâãžãªãã·ãïŒ ïŒåŒäžãã¯æ°ŽçŽ ããã³ãžã«ãŸãã¯ççŽ æ°ïŒãïŒ
ã®ã¢ã«ãã«ïŒïŒºã¯ïŒâããªãžã«ãã¢ã«ãã«çœ®æâ
ïŒâããªãžã«ãïŒâãã¢ãŸãªã«ãïŒåãŸãã¯ïŒå
ã®ã¢ã«ãã«åºã§çœ®æãããïŒâãã¢ãŸãªã«ããã
ãã¯ïŒâã¢ã«ãã«âïŒâã€ãœããµãŸãªã«ã§ããã
ããã§åã¢ã«ãã«ã¯ççŽ æ°ïŒãïŒã§ããïŒ ã®è£œæ³ã§ãã€ãŠãäžèšå·¥çš (a) åŒ ïŒåŒäžãR1ã¯ãã³ãžã«ãŸãã¯ççŽ æ°ïŒãïŒã®
ã¢ã«ãã«ïŒ ã®ãšã¹ãã«ãšåŒZNH2ã®ã¢ãã³ãšãåå¿äžæŽ»æ§
ææ©æº¶åªã®ååšäžçŽïŒã110âã®æž©åºŠã§æ¥è§Šã
ããŠåŒ ã®äžéäœãçæãã (b) 該äžéäœãåé¢ãããã®äžéäœãåå¿äžæŽ»æ§
溶åªäžçŽ120ã200âã®æž©åºŠã§å ç±ããããšãã
ãªãæ¹æ³ã«é¢ããã æ¬çºæã®åŒïŒïŒã®ååç©ããã³æ¬çºæã®å·¥çš
äžã眮æåºïŒ²ãR1ããã³ïŒºãšããŠç¹ã«å¥œé©ãªã®
ã¯ã次ã®ãã®ã§ããïŒ ïŒ²ã¯ïŒããïŒåã®ççŽ ååãæããã¢ã«ãã«åº
ã§ããã R1ã¯ãïŒããïŒåã®ççŽ ååãæããã¢ã«ã
ã«åºã§ããã ãããŠïŒºã¯ãïŒâããªãžã«åºãïŒâãã¢ãŸãªã«
åºãïŒâã¡ãã«âïŒâã€ãœããµãŸãªã«åºãïŒâã¡
ãã«âïŒâããªãžã«åºããŸãã¯ïŒïŒïŒâãžã¡ãã«
âïŒâãã¢ãŸãªã«åºã§ããã äžè¿°ã®çœ®æåºãšããŠããã«ç¹ã«å¥œé©ãªã®ã¯æ¬¡ã®
ãã®ã§ããïŒ ïŒ²ã¯ã¡ãã«åºã§ããã R1ã¯ã¡ãã«åºãŸãã¯ãšãã«åºã§ããããã㊠ã¯ãïŒâããªãžã«åºãïŒâãã¢ãŸãªã«åºãŸã
ã¯ïŒâã¡ãã«âïŒâã€ãœããµãŸãªã«åºã§ãããæ¬
çºæã®æã奜é©ãªååç©ã¯ãåŒäžã®ïŒ²ããã³R1
ãåã ã¡ãã«åºã§ãã€ãŠïŒºãïŒâããªãžã«åºã§ã
ããåŒïŒïŒã®ååç©ã§ãããæ¬çºæã®å·¥çšã«ã
ã€ãŠåŸãããçžåœããåŒïŒïŒã®æççå€ã¯ãç·
称çã«ãããã¯ã·ã«ã ïŒpiroxicamïŒããšããŠç¥
ãããŠãããäŸãã°ãã¯ã€ãºãã³ïŒWisemanïŒã
Roy.Soc.Med.Int.Cong.Symp.Ser.ïŒã11â23
ïŒ1978ïŒãåç §ããããã æ¬çºæã®æ¹æ³ã¯ãæ¹è¯ãããåçãšå¢å€§ããã
çç£æ§ãšããå©ç¹ãæãã溶åªã®äœç©ãããããª
ãå€ééã®åŒïŒïŒã®çæç©ãäžãããæ¬çºæã®
å·¥çšã«ãã€ãŠåŸãããåŒïŒïŒã®çæç©ã¯ããŸã
æ¹è¯ãããçŽåºŠããæããŠãããæ¬çºæã®å·¥çšã®
ãã®äžã®å©ç¹ã¯ãæ¯æ¶²ã次ã®ããããžç¹°ãè¿ãå
埪ç°ãããããšãã§ããããã«ãã€ãŠå¥œçµæãåŸ
ãããããšã§ããã æ¬çºæã®å·¥çšã«ãããåŒïŒïŒã®äžéäœã®åé¢
ã«ãã€ãŠãå è¡æè¡ã®å·¥çšã«ãããŠã¯äžå¯èœã§ã
ã€ãä»å çãªç²Ÿè£œãè¡ãªãããšãã§ãããããã
ãŠããã®æ¹æ³ã§ã¯ãäžéäœååç©ïŒïŒã®åé¢ã«
ãã€ãŠç²Ÿè£œããããããããçŽåºŠã®äœãåºçºç©è³ª
ãçšããããšãã§ããããã®ããšã¯ãæççå€
ïŒïŒã®çŽåºŠãäœäžãããããšãªãäžçŽãªã¢ãã³
ZNH2ã䜿çšããããšãã§ãããããæãããªå©
ç¹ã§ãããããã«ãäžã«å®çŸ©ãããããªåŒZNH2
ã®ã¢ãã³ã¯ãå è¡æè¡ã®æ¹æ³ã«ãã€ãŠã¯ç²Ÿè£œãå°
é£ã§ããããšã¯ãåœåéã§å ¬ç¥ã§ããã æ¬çºææ¹æ³ã«ãããã®åŒïŒïŒã®ååç©ã¯ãã»
ãŒçã¢ã«éã®ãåŒïŒïŒã®ïŒâãªããœâïŒïŒïŒâ
ãã³ãŸãã¢ãžã³âïŒâã«ã«ãã³é žãšã¹ãã«ãšé©åœ
ãªã¢ãã³ãZNH2ïŒåŒäžïŒºã¯å ã«å®çŸ©ããéãã§
ããïŒãšãæ¥è§Šãããããšã«ãã€ãŠåŸããããã
ã®åå¿ã¯ãåå¿ã«äžæŽ»æ§ãªææ©æº¶åªã®ååšã«ãã
ãŠã枩床çŽïŒãã110âãããã³åå¿æé24æé
ãŸã§ãã§å®æœãããããã®åå¿ã«å¯Ÿããç¹ã«å¥œé©
ãªæž©åºŠç¯å²ã¯çŽ20ãã90âã§ããããã®æž©åºŠã§
ã¯ããã®åå¿ã¯éåžžæ°åããæ°æéãäŸãã°15å
ããçŽïŒæéã§å®äºããããã®åŸãææãªãã°åŒ
ïŒïŒã®çæç©ã¯ãäŸãã°ããã®åå¿æ··åç©ã宀
æž©ãŸãã¯ãã以äžã«å·åŽããæ²æŸ±ããåºäœãé
ããŠéãããããŠä¹Ÿç¥ãããããšã«ãã€ãŠãåé¢
ãããã ãã®äžã§éå®ãããåå¿ã«äžæŽ»æ§ãªææ©æº¶åª
ã¯ãçšããããåå¿æ¡ä»¶ã§åºçºç©è³ªãŸãã¯åå¿ç
æç©ã®ã©ã¡ããšãç®ã«èŠããã»ã©åå¿ããããã
ãåå¿æž©åºŠãŸãã¯ãã以äžã®æž©åºŠã§ãå°ãªããšã
å®è³ªåã®åºçºç©è³ªã溶解ãããããšãã§ãããã®
ã§ãããããã«ãäžèšã®æº¶åªã¯ãåœæè¡åéã«ç¿
çãã人ã«ã¯å ¬ç¥ã®æšæºçãªæè¡ã«ãã€ãŠææã®
çæç©ããã®æº¶åªãã容æã«ååã§ãããã®ã§ã
ããåŒïŒïŒã®ææã®ååç©ã®è£œé ã«äœ¿çšããåŸ
ããåå¿ã«äžæŽ»æ§ãªææ©æº¶åªã®äŸã¯ããã³ãŒã³ã
ãã«ãšã³ããã·ã¬ã³é¡ããšãã«ãã³ãŒã³ãããã©
ãªã³ããã³ãã«ãªã³ã®ãããªçåæ°ŽçŽ é¡ïŒã¯ãã
ãã«ã ãäºå¡©åã¡ãã¬ã³ãäºå¡©åãšãã¬ã³ãèå
ãšãã«ããã³äºèåãšãã¬ã³ã®ãããªããã²ã³å
çåæ°ŽçŽ é¡ïŒã¢ã»ãã³ããã³ã¡ãã«ãšãã«ã±ãã³
ã®ãããªã±ãã³é¡ïŒãšãã«ãšãŒãã«ãããã©ãã
ããã©ã³ãïŒïŒïŒâãžã¡ããã·ãšã¿ã³ããã³ãžãš
ãã¬ã³ã°ãªã³ãŒã«ãžã¡ãã«ãšãŒãã«ã®ãããªãšãŒ
ãã«é¡ïŒãžã¡ãã«ãã«ã ã¢ããããžã¡ãã«ã¢ã»ã
ã¢ããããã³ïŒ®âã¡ãã«âïŒâãããªãžãã³ã®ã
ããªãžã¢ã«ãã«ã¢ããé¡ïŒãžã¡ãã«ã¹ã«ããã·ã
ããã³ã¢ã»ããããªã«ïŒã§ãããç¹ã«å¥œé©ãªã®
ã¯ãå°ããšããçšããããæé«åå¿æž©åºŠãšåãäœ
é«ã倧æ°æ²žç¹ãæãããäžè¿°ã®æº¶åªã§ãããç¹ã«
奜é©ãªã®ã¯ãçµæžæ§ããã³å¹çã®ãããåçšæ··å
ãã·ã¬ã³ã§ããã åŒïŒïŒã®çæç©ã«é¢ããæåã®ç 究ã§ã¯ãã
ã®ãããªåå¿ã®ããã®å€å žçãªïŒäžå®å®ãªïŒäžé
äœã«é¡äŒŒããæ§é ã圢æããããã®ãã¢ãã³ãšãš
ã¹ãã«ãšã®éã®å ±æçµåã瀺åããããããããª
ãããããã«ç 究ããçµæã¯ãïŒïŒïŒã¢ã«ä»å ç©
ããå®éšåŒïŒïŒã®ååç©ã®æ§é ãããæ£ç¢ºã«è¡š
ãããšã匷ã瀺åããŠããã 13CâNMRããã³
1HâNMRã¹ãã¯ãã«èšŒæ ããã³èµ€å€ã¹ãã¯ã
ã«ã«ãããäºã€ã®ã«ã«ããã«åž¯ã®ååšã¯ãç¹ã«ã
ãã®ãããªä»å ç©ãšäžèŽããŠããã äžè¿°ããããã«ãåŒïŒïŒã®ååç©ã¯ãR1OH
ã®é€å»ã«ããåŒïŒïŒã®æççå€ã®çæã«ããã
äžéäœãšããŠæçšã§ããã äžã®åå¿ããŸããäžã«éå®ãããç¹ã«å¥œé©ãªå
å¿ã«äžæŽ»æ§ãªææ©æº¶åªã®äžã€ã®ååšã«ãããŠå®æœ
ãããããäœãã枩床ã¯ãåå¿äžã«çºçããã¢ã«
ã³ãŒã«ãè¿œãåºãããã«ãé«ãããã枩床ã§å®æœ
ãããããã®åå¿ã«å¥œé©ãªæž©åºŠã¯ãçŽ120ãã200
âã§ãããç¹ã«å¥œé©ãªã®ã¯çŽ135ãã145âã§ã
ãã äžèšåå¿ã«ããåŒïŒïŒã®ååç©ã®çæã«äœ¿çš
ããåŸããåå¿ã«äžæŽ»æ§ãªææ©æº¶åªã¯ã奜é©ãªæž©
床ç¯å²ããå®è³ªçã«äœã枩床ã§æ²žãšãããã®ãã
é«å§è£ 眮ã®äœ¿çšãå¿ èŠãšããã§ããã溶åªãé€ã
ãŠãæ¬çºæã®åŒïŒïŒã®ååç©ã®çæã®ããã«äž
ã«ç€ºãããã®ãšåãã§ããããã®åå¿ã«ç¹ã«é©ã
ã溶åªã¯ãããªãšã³ããã·ã¬ã³é¡ããšãã«ãã³ãŒ
ã³ãããã©ãªã³ããã³ãã«ãªã³ã§ããïŒãããŠæ
ã奜é©ãªã®ã¯ãçµæžæ§ãšå¹çã®ç¹ãããæ··åãã·
ã¬ã³ã§ããããã¡ãããåœåéã«ç¿çãã人ã«èª
ããããéãæ··åãã·ã¬ã³ã¯ã枩床å¶åŸ¡ãšå¯çæ
ç©ã®ã¢ã«ã³ãŒã«ãR1OHã®é€å»ãšã容æã«ããç¹
城ã§ãããç¹ã«å¥œé©ãªæž©åºŠç¯å²å ã®æ²žç¹ãæãã
ãšããå©ç¹ãæããŠããã æ¬çºæã®å·¥çšã®ç¬¬äžæ®µéã«ãããŠã¯ãåŒïŒïŒ
ã®åºäœäžéäœçæç©ã®åœ¢æã¯ããšã¹ãã«ïŒïŒãš
ã¢ãã³ZNH2ãåå¿ãããŠçŽæ¥ïŒïŒã圢æãã
ãå è¡æè¡ã®å·¥çšã§ã¯äžå¯èœãªç²Ÿè£œæ³ãäžããã
ãã®ãããæ¯èŒçäžçŽãªåŒïŒïŒããã³ZNH2ã®
åºçºç©è³ªãããã®æ¹æ³ã«ãããŠã¯äœ¿çšãããããš
ãã§ãããããŠæççå€ïŒïŒã«å€æããåã«ã
æ°èŠãªåŒïŒïŒã®äžéäœãåé¢ããããšã«ãã€ãŠ
粟補ãè¡ãªãããšãã§ããã æ¬çºæã®æ¹æ³ã®ããã«å¥ã®å©ç¹ã¯ãææã®çæ
ç©ïŒïŒãæ¹è¯ãããåçã§ãããããæã奜ãŸ
ããå è¡æè¡æ¹æ³ãããªãã¡ãçžåœããïŒâã«ã«
ãã³é žãšã¹ãã«ãšZNH2ïŒïŒºã¯ãã®äžã§å®çŸ©ãã
éãã§ããïŒã®ãããªè€çŽ ç°åŒã¢ãã³ãçµããã
ã³ãŸãã¢ãžã³âïŒâã«ã«ãããµããã®çæã«ã€ã
ãŠäžè¿°ããç±³åœç¹èš±ç¬¬3591584å·ã®æ¹æ³ã«ã€ããŠ
å¯èœã§ãããããããã«å€§ããªåŠçéã§ãåŸãã
ãããšãã§ããããšã§ãããå è¡æè¡æ³ã«ãããŠ
ã¯ã溶åª100mlãããçŽïŒïœãã倧ããªå šåå¿äœ
æ¿åºŠãçšãããããšããåå¿æ··åç©ã¯æ¯èŒçé«æ°Ž
æºã®å解çæç©ãšçè²äœãçæãããããåŒ
ïŒïŒã®ææçæç©ã®åé¢ãå°é£ã«ãããã以äž
ã®è²»çšã®ããã粟補段éãªãã«ã¯è¬åŠç䜿çšã«é©
ããªãäžçŽãªçæç©ãäžããã ããããªãããæ¬çºæã®å·¥çšã¯ãçæç©ã®åé
ãŸãã¯ãã®çŽåºŠãç ç²ã«ããããšãªããåŠçéã
段é(b)ã«ãããŠ100mlãããïŒâïŒã°ã©ã ãŸãã¯
ãã以äžã«å¢å€§ãããããšã®ã§ãããããªæ¹æ³ã§
å®æœãããããšãã§ãããããã¯æ®µé(a)ã§åŸãã
ãåŒïŒïŒã®æ°èŠãªäžéäœååç©ãåé¢ãããã
ãæ°åã«åããŠã段é(b)ã§çšããããå ç±ããã
溶åªæ··åç©ã«å ããŠãèŠçŽ R1OHãé€å»ãçæç©
ïŒïŒãé«åçããã³é«çŽåºŠã§åœ¢æãããããšã«
ãã€ãŠéæãããã æ¬çºæã®å·¥çšã«ã€ããŠèšŒæãããããšã®ã§ãã
ããã«ããäžã€ã®å©ç¹ã¯ãæ¯æ¶²ã次ã®åå¿æäœã«
ããè¿ãå埪ç°ãããããããšãã§ããããšã§ã
ããæ¬å·¥çšã«ãããŠæ¯æ¶²ãããè¿ãå埪ç°ããã
åŸã«ãé«åçé«çŽåºŠã®çæç©ã芳å¯ãããããã
ãŠæ¯æ¶²äžã«ä¿çãããçæç©ã®æ倱ãé¿ããã
ãããããšå¯Ÿç §çã«ãå埪ç°ãå è¡æè¡å·¥çšã«ã€
ããŠå®æœãããšãã¯äžçŽç©ã®å ç©ããäºã»äžåã®
æ¯æ¶²ã®å埪ç°åŸã«ã¯éåžžã«å€§ãããªã€ãŠãææã®
çæç©ãåé¢ããããšãã§ããªããããããã¯é
åžžãªå°é£ã䌎ãªã€ãŠããåé¢ããããšãã§ããª
ãã 以äžã®å®æœäŸã¯ãç¹èš±è«æ±ãããçºæã説æã
ããã®ã§ãããNMRã®ããŒã¯ã®å€é床ã«å¯ŸããŠ
次ã®çç¥ãçšããããïŒ ïœãåäžç·ïŒïœãäºéç·ïŒïœãäžéç·ïŒïœã®
ïœãäžéç·ã®äºéç·ïŒïœãåéç·ïŒïœãå€éç·ã åèäŸ ïŒ åŒïŒïŒãïŒR1ïŒCH3ãZ1ïŒïŒâããªãžã«åº
ã®çµæ¶æ§ååç© çªçŽ é°å²æ°äžã§ã300mlã®ãã·ã¬ã³äžã®120ïœ
ïŒ0.446ã¢ã«ïŒã®3.4âãžãããâïŒâã¡ãã«âïŒ
âãªããœâ2HâïŒïŒïŒâãã³ãŸãã¢ãžã³âïŒâ
ã«ã«ãã³é žã¡ãã«âïŒïŒïŒâãžãªãã·ãã®æº¶æ¶²
ã«ã48ïœïŒ0.510ã¢ã«ïŒã®ïŒâã¢ããâããªãžã³
ãå ããããã®æ··åç©ããã¯ãããããã¯ãããª
ãã80âã«å ç±ãããã®æž©åºŠã«ïŒæéä¿ã¡å®€æž©ãŸ
ã§å·åŽããéããŠä¹Ÿç¥ããããšãææã®é¯åå
ç©158.6ïœïŒ98ïŒ ïŒããé»è²ã®çµæ¶ãèç¹132â
133âããšããŠåŸãããã è©ŠæããïŒïŒïŒïŒäœç©æ¯ïŒã¡ã¿ããŒã«ïŒæ°Žäžã®
0.50Nã®å¡©é žã§æ»Žå®ãããšãäžååœéã¯367.6ïŒç
è«å€363ïŒã§ãã€ãã質éã¹ãã¯ãã«ïŒïœïŒïœ ïŒ
芪ããŒã¯ã¯331ãèµ€å€ã¹ãã¯ãã«ïŒKBrïŒcm-1ïŒ
1675ããã³1660cm-1ã§åŒ·ãã«ã«ããã«åºã®åžåã åæïŒC16H17N3O5SãšããŠã® èšç®å€ïŒïŒ£ã52.89ïŒïŒšã4.72ïŒïŒ®ã11.56 å®æž¬å€ïŒïŒ£ã52.88ïŒïŒšã4.77ïŒïŒ®ã11.66 250MHz 1HâNMRïŒCDCl3ïŒppmïŒãã«ã¿ïŒïŒ ppm å€é床 ç©å 8.05 ïœ ïŒ 7.88 ïœ ïŒ 7.73 ïœ ïŒ 7.44 ïœã®ïœ ïŒ 6.60 ïœã®ïœ ïŒ 6.52 ïœ ïŒ 3.97 ïœ ïŒ 2.96 ïœ ïŒ 13CâNMRïŒDMSOïŒïŒ ç· ppm å€é床 ïŒ 167988 ïœ ïŒ 158917 ïœ ïŒ 158449 ïœ ïŒ 146076 ïœ ïŒ 137673 ïœ ïŒ 134902 ïœ ïŒ 133005 ïœ ïŒ 132743 ïœ ïŒ 128662 ïœ 10 126557 ïœ 11 123381 ïœ 12 111736 ïœ 13 109330 ïœ 14 108609 ïœ 15 52458 ïœ 16 38489 ïœ ããã·ã¯ãã«ã ïŒpiroxicamïŒãšïŒïŒïŒâãžã
ããâïŒâã¡ãã«âïŒâãªããœâ2HâïŒïŒïŒâ
ãã³ãŸãã¢ãžã³âïŒâã«ã«ãã³é žã¡ãã«ïŒïŒïŒâ
ãžãªãã·ããšã® 13CâNMRã¹ãã¯ãã«ã®æ¯èŒã®
ããã«ãŠã€ããã«ïŒWhippleïŒããªã«ã¬ããã¯ã»
ãã°ããã€ãã¯ã»ã¬ãŸãã³ã¹ïŒOrganic
Magnetic ResonanceïŒã10ã23ïŒ1977ïŒãåç §ã
ãããã ãžã¡ãã«ã¹ã«ããã·ãäžã®äžèšçæç©ã®è©Šæ
ã«ãïŒïŒïŒâãžãããâïŒâã¡ãã«âïŒâãªããœ
â2HâïŒïŒïŒâãã³ãŸãã¢ãžã³âïŒâã«ã«ãã³
é žã¡ãã«ïŒïŒïŒâãžãªãã·ã1.0åœéãæ·»å ãã
ãšã 13CâNMRã¹ãã¯ãã«ã®ç·ã®ãã¡11ãå¢å€§
ããååŠã·ããã¯ãããã«å€åããããã®ããš
ã¯ã溶液äžã§ã¯NMRæéç®çã®éã«ãã°ãã亀
æãããããšãã¯ã€ãã瀺ããŠããã ç·åæã®ããã«ãäžèšã§åŸãããçæç©ã宀
æž©ã§ã¢ã»ãã³ããçµæ¶åãããŠå€§ããªé»è²ç«æ¹äœ
ã®çµæ¶ãåŸããèç¹132âïŒéãïŒ ïŒžç·ããŒã¿ããã次ã®ããšãçµè«ãããã (ã€) ãšããŒã«æ§ãããã³ã¯ïŒâã¢ããããªãžã³ã®
ç°äžã®çªçŽ ããã³ãšã¹ãã«ã«ã«ããã«é žçŽ åå
ã«çµåããæ°ŽçŽ ã§ããããšïŒ (ã) ïŒâã¢ããåºã®ãããã³ã®ãã¡ã®ïŒã€ã¯ãšã
ãŒã«æ§é žçŽ ååã«çµåãããŠããããšïŒ (ã) ä»ã®ïŒâã¢ãããããã³ã¯äžèšçæç©ã®ãã
ïŒã€ã®ååã®ã¹ã«ãã³ã®é žçŽ ååã«çµåããã
æ°ŽçŽ ã§ããããšïŒ (ã) äžèšçæç©ã®æ§é ã¯äžèšåŒã«ãã€ãŠè¡šããã
ãïŒ ïŒåŒãïŒR1ïŒCH3ãZ1ã¯ïŒâããªãžã«ç°
ãå®æããïŒ åèäŸ ïŒ 13mlã®ã¢ã»ãã³ã«ã2.69ïœïŒ0.01ã¢ã«ïŒã®ïŒïŒ
ïŒâãžãããâïŒâã¡ãã«âïŒâãªããœâ2Hâ
ïŒïŒïŒâãã³ãŸãã¢ãžã³âïŒâã«ã«ãã³é žã¡ãã«
ïŒïŒïŒâãžãªãã·ãããã³0.94ïœïŒ0.01ã¢ã«ïŒã®
ïŒâã¢ããããªãžã³ãå ããæ··åç©ãæž©ããŠæº¶æ¶²
ãšããããã®é»è²ã®æº¶æ¶²ããæ²æŸ±ãå®äºãããŸã§
å·èµããŠãéããé»è²ã®çµæ¶ã也ç¥ãããŠãå
åç©ïŒïŒãïŒR1ïŒCH3ãïŒïŒâããªãžã«
åºãèç¹132â133âã84ïŒ ã®åçã§åŸãã äžèšã®å·¥çšããåãèŠæš¡ã§ãã¢ã»ãã³ã®ä»£ãã«
çš®ã ã®åå¿ã«äžæŽ»æ§ãªææ©æº¶åªãçšããŠãããè¿
ãããã®çµæãäžã®è¡šã«èŠçŽããã ãè¡šã ãã«æž©
ãã
ãè¡šã ããŠæ²æŸ±ã
ãã
äžã®åå¿ãã溶åªãšããŠã®ã¢ã»ãã³äžã§ããã
ïŒã¢ã«éå°ã®ã¡ãã«ãšã¹ãã«ãŸãã¯ïŒâã¢ããã
ãªãžã³åå¿äœãçšããŠããè¿ããšãã¯ãåãçæ
ç©ãé»è²çµæ¶ãèç¹132â134âãšããŠåŸãããã
ãšã¹ãã«åå¿äœïŒïŒãéå°ã«çšãããšãããã
ã¯æã«ã¯ãã©ã¹ã³ã®åŽé¢ã«ä»çããçœè²åºäœãšã
ãŠããããããã®ãã®ã¯åŒïŒïŒã®é»è²çµæ¶ãã
容æã«åé¢ãããã ãã®å·¥çšãïŒâã®ããã©ããããã©ã³äžãŸãã¯
110âã®ãã«ãšã³äžã§ããè¿ããšããçµæã¯å®è³ª
äžåäžã§ããã åèäŸ ïŒ ïŒïŒïŒâãžãããâïŒâã¡ãã«âïŒâãªããœâ
2HâïŒïŒïŒâãã³ãŸãã¢ãžã³âïŒâã«ã«ãã³é ž
ã¡ãã«ïŒïŒïŒâãžãªãã·ããé©åœãªåŒïŒïŒã®å
åç©ã§çœ®ãæããŠãåèäŸïŒãŸãã¯ïŒã®å·¥çšãã
ãè¿ããšããçžåœããããïŒâããªãžã«åºã§ã
ãåŒïŒïŒã®ååç©ãåŸãããã  R1 CH3 C2H5 CH3 ïœâC3H7 C2H5 ïœâC3H7 C6H5CH2 ïœâC4H9 CH3 ïœâC4H9 ïœâC3H7 ïœâC4H9 ïœâC3H7 secâC4H9 C6H5CH2 CH3  ïœâC4H9  C2H5 åèäŸ ïŒ åŒïŒïŒãïŒR1ïŒCH3ãïŒïŒâãã¢ãŸãªã«
åºãã®çµæ¶æ§ååç© çªçŽ äžã§ããã¯ããããïŒïŒïŒâãžãããâïŒ
âã¡ãã«âïŒâãªããœâ2HâïŒïŒïŒâãã³ãŸã
ã¢ãžã³âïŒâã«ã«ãã³é žã¡ãã«ïŒïŒïŒâãžãªãã·
ã2.69ïœïŒ10ããªã¢ã«ïŒãšãã·ã¬ã³50mlãšã®æ··å
ç©ã«ã1.05ïœïŒ10.5ããªã¢ã«ïŒã®ïŒâã¢ãããã¢
ãŸãŒã«ãå ããããã®æ··åç©ãïŒæé85â90âã«
å ç±ãã宀枩ãŸã§å·åŽããŠéããããŠè€è²ã®çµ
æ¶æ§çæç©ãç空也ç¥ãããŠè¡šé¡ååç©2.3ïœ
ïŒ62.3ïŒ ïŒãèç¹131â141âãåŸãã ãã®çµæ¶çæç©ã20mlã®å¡©åã¡ãã¬ã³ã«æº¶è§£ã
ãã掻æ§çãå ããŠè±è²ããåŸéããããã®
液ãååã«ããã¯ãããªãããããµã³ã«æ·»å ãïŒ
æéç²ç ãããã®åŸéãããšçœè²çµæ¶çæç©ïŒ
èç¹140ã145âãã1.35ïœåŸãããã 溶åªãšããŠã¢ã»ãã³ãå¡©åã¡ãã¬ã³ããšãã«ãš
ãŒãã«ãäºèåãšãã¬ã³ãïŒïŒïŒâãžã¡ããã·ãš
ã¿ã³ããã³ãŒã³ããžã¡ãã«ãã«ã ã¢ããããžã¡ã
ã«ã¢ã»ãã¢ããããšãã«ãã³ãŒã³ããã«ãšã³ãŸã
ã¯ãã«ãªã³ãçšããŠæž©åºŠïŒâ110âã§ïŒâ24æéã
äžèšå·¥çšãããè¿ããšããåŒïŒïŒã®ææã®çæ
ç©ãåæ§ã«åŸãããã åèäŸ ïŒ é©åœãªãåŒïŒïŒããã³ZNH2ã®åºçºç©è³ªãçš
ããããšã«ãã€ãŠãåèäŸïŒâïŒã®å·¥çšã«ãã€ãŠ
次ã®åŒïŒïŒã®ååç©ãåŸãããã ãè¡šã ãè¡šã ãžã«
ãè¡šã ãè¡šã ãã¢ãŸãªã«
åèäŸ ïŒ ããã¯ã·ã«ã ã®æšæºç補é æ³ æž©åºŠèšãå å¡«èžçå¡ãå·åŽæ©ããã³ããã¯ãæ©
ããšãã€ããïŒãªããã«ãã©ã¹ã³ã«ãçªçŽ ç²å²æ°
äžã§ãæ··åãã·ã¬ã³3300mlãïŒïŒïŒâãžãããâ
ïŒâã¡ãã«âïŒâãªããœâ2HâïŒïŒïŒâãã³ãŸ
ãã¢ãžã³âïŒâã«ã«ãã³é žã¡ãã«ïŒïŒïŒâãžãªã
ã·ã80ïœïŒ0.297ã¢ã«ïŒãïŒâã¢ããããªãžã³32ïœ
ïŒ0.340ã¢ã«ïŒããã³æŽ»æ§çïŒDarco â60â»ãŸ
ãã¯Darco KBBâ»ïŒïŒïœãå ããããã®æ··åç©
ã28æéå ç±éæµïŒçŽ140âïŒããããããã®éã
æåã®ïŒæéã¯æ¯æçŽ25mlã®é床ã§ãã®åŸæ®ãã®
éæµæéã¯æ¯æïŒâ10mlã®é床ã§ãã¡ã¿ããŒã«ãš
ãã·ã¬ã³ãšãèžçããŠé€ããäžæ¹ã§æ°ãããã·ã¬
ã³ãå ããŠåå¿ç©ã®å®¹ç©ãçŽ3500mlã«ä¿ã€ã28æ
éåŸã«ããã®åå¿æ··åç©ãå°ãå·åŽãïŒã100
âïŒãéããŠççŽ ãé€å»ããããã®ççŽ ã±ãŒã
ãæž©ãã·ã¬ã³ïŒ100mlïŒã§æŽæµãã液ãšæŽæµæ¶²
ãè¿ éã«ããããããªããçªçŽ é°å²æ°äžã§25â50
âãŸã§ãã€ããå·åŽãããå®å šã«çµæ¶åãããã
ãã«ãïŒæéããã¯ããç¶ãããçµæ¶ãéã«ã
ã€ãŠéããæ¯æ¶²ãçŽ1500mlãŸã§æ¿çž®ããçªçŽ äžã§
ïŒâïŒâã«å·åŽããéããŠããã®ã±ãŒãã100
mlã®å·ãã·ã¬ã³ã§æŽæµãããããŠçµæ¶ãç空äž60
â以äžã§æ°æé也ç¥ããããåéã¯ã76.7â84.6
ïœïŒçè«éã®78â86ïŒ ïŒã§ãããå¹³ååŠçé24.4
ïœïŒæº¶åªã â»ã¢ã€ã»ã·ãŒã»ã¢ã€ã»ã¢ã¡ãªã«ç€Ÿ ïŒICIAmericaãInc.ïŒã®ç»é²åæš å®æœäŸ ïŒ äžéäœïŒïŒ©ãïŒR1ïŒCH3ãïŒïŒâããªãž
ã«åºïŒãçšããæ¹è¯ãããããã¯ã·ã«ã æ³ ïŒ¡ çªçŽ ã§ããŒãžããïŒãªããã«ãã©ã¹ã³ã«ãæ··
åãã·ã¬ã³300mlãïŒïŒïŒâãžãããâïŒâã¡
ãã«âïŒâãªããœâ2HâïŒïŒïŒâãã³ãŸãã¢
ãžã³âïŒâã«ã«ãã³é žã¡ãã«ïŒïŒïŒâãžãªãã·
ã120ïœïŒ0.446ã¢ã«ïŒããã³ïŒâã¢ããããªãž
ã³48ïœïŒ0.510ã¢ã«ïŒãå ããããã®æ··åç©ã
90âã«å ç±ãããã®æž©åºŠã§ïŒæéè¿ éã«ããã¯
ãããŠãããçªçŽ é°å²æ°äžã§å·åŽãããã 3300mlã®ãã·ã¬ã³ãå«æããïŒãªããã«ãã©
ã¹ã³ã«ã12ïœã®æŽ»æ§çïŒDarco â60ïŒãå
ãããã®æ··åç©ãå ç±éæµããããã®éã«åé¢
åšïŒãã«ã³ã¿ãŒäžã«ãã·ã¬ã³ïŒæ°Žãéãããã
ã®ãã®ã«ãäžã§åŸãäžèšã®åŒïŒïŒã®äžéäœå
åç©ã®ãã·ã¬ã³ã¹ã©ãªãŒã®ååãå ããããã®
æ··åç©ãéæµãããŠãã¡ã¿ããŒã«ïŒãã·ã¬ã³ã
æ¯æ25mlã®é床ã§èžçããŠé€ãããäžæ¹ã§æ°ã
ããã·ã¬ã³ãå ããŠåå¿äœç©ãçŽ3500mlã«ä¿æ
ãããïŒæéåŸã«ãæ®çããäžéäœååç©ã®ã¹
ã©ãªãŒã®ïŒåã®ïŒãå ããåãé床ã§ã¡ã¿ããŒ
ã«ïŒãã·ã¬ã³ã®èžçãç¶è¡ãããäžéäœã®æ®ç
éšïŒïŒåã®ïŒãŸãã¯æ®éšïŒãïŒæéããã³12æ
éã§åã å ãããããŠèžçã25mlïŒæã§ãå šäœ
ã§16æéç¶ããã16æéåŸã«ãèžçæ·»å ãæ¯æ
12.5mlã«äžããŠå šäœã§34æéç¶ããã åå¿æ··åç©ãçŽ100âãŸã§å·åŽããŠãéã
ãŠççŽ ãé€å»ãããã®ççŽ ã±ãŒãã100mlã®æž©
ãã·ã¬ã³ã§æŽæµããã液ãçªçŽ ã§ããŒãžã
ãŠãè¿ éã«ããã¯ãŒããªãã25â50âã«å·åŽã
ããå®å šã«çµæ¶ããããã«ïŒæéããã¯ããç¶
ããããã®çµæ¶ãéã«ãã€ãŠéããæ¯æ¶²ãæ¿
çž®ããŠçŽ1500mlãšããçªçŽ äžã§ïŒâïŒâã«å·åŽ
ããŠéããã±ãŒãã100mlã®å·ãã·ã¬ã³ã§æŽ
æµãããããŠçµæ¶æ§çæç©ã60â以äžã§ç空也
ç¥ããããããã¯ã·ã«ã ã®åéã¯ã121â132.8
ïœïŒçè«ã®82â90ïŒ ïŒã§ãããå¹³ååŠçé38.5
ïœïŒæº¶åªã  次ã®ããã«å€åœ¢ããŠäžèšå·¥çšãããè¿ãïŒçª
çŽ é°å²æ°äžã§ãæ··åãã·ã¬ã³600mlã«ã160ïœ
ïŒ0.594ã¢ã«ïŒã®ïŒïŒïŒâãžãããâïŒâã¡ãã«
âïŒâãªããœâ2HâïŒïŒïŒâãã³ãŸãã¢ãžã³
âïŒâã«ã«ãã³é žã¡ãã«ïŒïŒïŒâãžãªãã·ããš
60ïœïŒ0.637ã¢ã«ïŒã®å·¥æ¥éæã®ïŒâã¢ããã
ãªãžã³ãå ãããæ··åç©ãïŒæéã85â90âã«
å ç±ãã20â25âã«å·åŽãããã®æž©åºŠã§ïŒæé
ããã¯ããããããããŠåŸãããçµæ¶æ§äžéäœ
ãéã«ãã€ãŠéããŠã100mlã®å·ãã·ã¬ã³ã§
æŽæµããã秀éãã溶åªã§æ¹¿ã€ãçµæ¶ã®è©Šæã
ç空也ç¥ãããã也ç¥è©Šæã®å·®åèµ°æ»ç±é枬å®
ã¯132.9âã§åäžã®éãããŒã¯ã瀺ããã也ç¥
ããè©Šéã®ééãããåŒïŒïŒãïŒR1ïŒ
CH3ãïŒïŒâããªãžã«åºãã®äžéäœã®åéã
215.9ïœïŒ98ïŒ ïŒã§ããããšã決å®ãããã 3300mlã®æ··åãã·ã¬ã³ã«ãïŒïœã®ïŒâã¢ãã
ããªãžã³ãïŒïœã®æŽ»æ§çïŒDarco KBBïŒãå
ããç³»ã«æ°ŽåããªããªããŸã§æ··åç©ãå ç±ããŠ
éãã«éæµãããã®éã«ãã·ã¬ã³ïŒæ°Žãéã
ãããã®åŸ50mlã®ãã·ã¬ã³ãšæ··åããäžèšçµæ¶
æ§äžéäœ81ïœïŒä¹Ÿç¥ééåºæºïŒïŒ0.223ã¢ã«ïŒã
å ãããåå¿æ··åç©ãå ç±éæµãããŠã25mlïŒ
æã®é床ã§ã¡ã¿ããŒã«ïŒãã·ã¬ã³ãåé¢ããã
äžã§åŸã215.9ïœãå šãŠæ¶è²»ããããŸã§ïŒæé
æ¯ã«è¿œå ã®17ïœã®äžéäœãå ãããããã«ã¯çŽ
16æéãèŠããã20æéã«éãããŸã§25mlïŒæ
ã§ã®éæµãç¶ãããã®ãšãã«éæµé床ã12â13
mlïŒæã«äžãããå¿ èŠã«å¿ããŠãã·ã¬ã³ãæ·»å
ããããšã«ãã€ãŠãå šåå¿å®¹ç©ã3.3ãªããã«
ãš3.7ãªããã«ãšã®éã«ä¿ã€ãå šåå¿æé34æ
éåŸã«ãæ··åç©ãå·åŽããçæç©ãäžã®ïŒ¡éšã®
ããã«åé¢ãããšã165.3ïœïŒ84ïŒ ïŒã®ããã¯
ã·ã«ã ãåŸããããåŠçé50ïœïŒæº¶åªãªãã
ã«ã æ¯èŒäŸ æ¯æ¶²ã®å埪ç°ãçšãããæšæºããã¯ã·ã«ã æ³ãš
æ¹è¯ããã¯ã·ã«ã æ³ãšã®æ¯èŒ æšæºæ³ïŒåèäŸïŒïŒããã³æ¹è¯æ³ïŒå®æœäŸïŒïŒ
ãã第ïŒã第ïŒããã³ç¬¬ïŒæäœã®åã ã«ãããŠã
åã®æäœããã®æ¯æ¶²ãå埪ç°ãããŠãåã ïŒåã
ãè¿ãããçµæãäžã«èŠçŽããã ãè¡šã äœã®å¹³å
ãã®å埪ç°å®éšã®å段éã§ãæšæºæ³ãçšããã
ããã¯ããé«ãè²æ°Žæºãæããããã¯æŒžé²çã«ã
ãã«ã¯ã€ãããšããŠãããæšæºæ³ã«ãã第ïŒæäœ
ã§ã¯ãçµæ¶åãã²ããããããããšã®ã§ããªãã·
ãããã®ã¿ãåŸãããããããæ¯ã¹ãŠãæ¹è¯æ³ã§
ã¯ç¬¬ïŒæäœã§93ïŒ ã®åçãåŸããæšæºæ³ã§ã¯çæ
ç©ãåŸãããªãã€ãã®ã§ããã®å®éšã¯ãã®æç¹ã§
åæ¢ãããæ¹è¯æ³ã«ããã°ç¬¬ïŒæäœåŸã«ãæ¯æ¶²ã¯
ãŸã éæã§ããããããŠä»®ã«è¡ãªããããšãã
ã°ãããªãæå©ã«ããã以äžã®æäœã«äœ¿çšããã
ããšãã§ããã§ãããã å®æœäŸ ïŒ äžéäœãšããŠãåèäŸïŒã§è£œé ãããé©åœãªåŒ
ïŒïŒã®ååç©ãçšããŠãå®æœäŸïŒããã³æ¯èŒäŸ
ã®å·¥çšãããè¿ããšãã次ã®åŒïŒïŒã®çæç©ã
ãŸãæ¹è¯ãããåçããã³åŠçéã§åŸãããã åŒäžïŒ²ããã³R1ã¯åèäŸïŒã§å®çŸ©ããéãã§
ããã å®æœäŸ ïŒ å®æœäŸïŒã®å·¥çšããã³æ¯èŒäŸã®å埪ç°å·¥çšã§ã
åºçºç©è³ªãšããŠåèäŸïŒããã³ïŒã§è£œé ãããåŒ
ïŒïŒã®ååç©ãçšãããšã以äžã®åŒïŒïŒã®ç
æç©ããŸãæ¹è¯ãããåçããã³åŠçéã§åŸãã
ãã åŒäžãããã³ïŒºã¯ãåèäŸïŒããã³ïŒã§å®çŸ©
ããéãã§ããã å®æœäŸ ïŒ äžéäœïŒãïŒR1ïŒCH3ãïŒïŒâãã¢ãŸ
ãªã«åºïŒãçšããæ¹è¯ã¹ããã·ã«ã
ïŒSudoxicamïŒæ³ ãã·ã¬ã³30mlãšãå ã«åŸãåŒïŒïŒã®çµæ¶æ§ïŒ
âãã¢ãŸãªã«äžéäœ0.5ïœãšãå«æãããã©ã¹ã³
ãã2.5æéãããïŒmlã®é床ã§ãã€ããèžçã
ããããããããã·ã¬ã³ïŒïŒmlïŒãšäžéäœ0.25ïœ
ãå ããäžã®ããã«èžçãããè¿ããããã«ãã
äžåºŠãããããè¿ããåŸãæ··åç©ãå šäœã§ïŒæé
ç°æµãããããã®åŸæ··åç©ãé±æ«äžïŒã60æéïŒã
åšå²æž©åºŠã§ããã¯ãããéããŠãããã¯ã·ã«ã
ã®ïŒâãã¢ãŸãªã«åæäœã§ãããçæç©ã¹ããã·
ã«ã ïŒSudoxicamïŒã65ïŒ åçïŒ590mgïŒãèç¹
245â247âïŒå解ïŒããé€å»ããã
çå€ã®æ¹è¯ããã補é æ³ã«é¢ããã â眮æããããã³ãŸãã¢ãžã³ã«ã«ãããµãã
æççå€åæã®ããã®äºã€ã®æ¹æ³ããç±³åœç¹èš±ç¬¬
3591584å·ã«ç€ºãããŠããããããã®ãã¡ã®ç¬¬äž
ã®ãã®ã¯ãâ眮æåºãè€çŽ ç°æåã§ãªãã«ã«ã
ããµããã補é ããããã«çšãããããããã¯ã
ææ©ã€ãœã·ã¢ããŒããR3NCOïŒåŒäžR3ã¯äŸãã°
äžå®ã®ã¢ã«ãã«åºãããšãã«åºãŸãã¯ãããã«åº
ã§ããïŒããïŒâãªããœïŒãŸãã¯ïŒâãªããœïŒ
ïŒïŒïŒâãã³ãŸãã¢ãžã³ãšæ¥è§ŠãããŠãäŸãã°åŒ ã®ååç©ãŸãã¯çžåœããïŒâãªããœâïŒâã«ã«ã
ããµãããçæãããããšã«ããæãã 第äºã®æ¹æ³ã¯ãâ眮æåºãè€çŽ ç°æåã§ã
ãããããã®ã¢ããã®è£œé ã«å¥œé©ã§ããïŒãã®æ¹
æ³ã¯ãææã®ãã³ãŸãã¢ãžã³ã«ã«ãããµãããç
æããããã®ãçžåœããã«ã«ãã³é žãšã¹ãã«ãšé©
åœãªã¢ãã³ãR2NH2ïŒR2ã¯è€çŽ ç°åºã§ããïŒãšã®
åå¿ã äŸãã°ã ãå å«ããã ç±³åœç¹èš±ç¬¬3891637å·ã«ã¯ãã¢ããåºè»¢ç§»å·¥çš
ã«ãã€ãŠãåŒïŒïŒã®ïŒ®âè€çŽ ç°ã¢ãããçžåœã
ãâããšãã«ã¢ããããåŸãæ¹æ³ã瀺ãããŠã
ãã ç±³åœç¹èš±ç¬¬3853862å·ã«ã¯ãéå±æ°ŽçŽ åç©ã®å
åšã«ããããã³ãŒã³ã¹ã«ããã«ã°ãªã·ã³ã¢ãã
ïŒïŒã®ç°åã«ãããåŒïŒïŒã®ïŒâãªããœâïŒïŒ
ïŒâãã³ãŸãã¢ãžã³âïŒâã«ã«ãããµããã®è£œé
æ¹æ³ãäŸãã° ã瀺ãããŠããã 1981幎ïŒæ15æ¥çºè¡ã®ç±³åœç¹èš±ç¬¬4289879å·ã«
ã¯ãçžåœããïŒâïŒïŒâã¡ããã·ãšãã«ïŒãšã¹ã
ã«ãçµç±ãããããã¯ã·ã«ã ïŒpiroxicamïŒãïŒ
âããããã·âïŒâã¡ãã«ââïŒïŒâããªãžã«ïŒ
â2HâïŒïŒïŒâãã³ãŸãã¢ãžã³âïŒâã«ã«ãã
ãµããïŒïŒïŒâãžãªãã·ããã®è£œæ³ãèšèŒãããŠ
ããã æ¬çºæã¯æ¬¡åŒã®ïŒïŒïŒâãžãããâ2HâïŒïŒ
ïŒâãã³ãŸãã¢ãžã³âïŒâã«ã«ãããµããâïŒïŒ
ïŒâãžãªãã·ãïŒ ïŒåŒäžãã¯æ°ŽçŽ ããã³ãžã«ãŸãã¯ççŽ æ°ïŒãïŒ
ã®ã¢ã«ãã«ïŒïŒºã¯ïŒâããªãžã«ãã¢ã«ãã«çœ®æâ
ïŒâããªãžã«ãïŒâãã¢ãŸãªã«ãïŒåãŸãã¯ïŒå
ã®ã¢ã«ãã«åºã§çœ®æãããïŒâãã¢ãŸãªã«ããã
ãã¯ïŒâã¢ã«ãã«âïŒâã€ãœããµãŸãªã«ã§ããã
ããã§åã¢ã«ãã«ã¯ççŽ æ°ïŒãïŒã§ããïŒ ã®è£œæ³ã§ãã€ãŠãäžèšå·¥çš (a) åŒ ïŒåŒäžãR1ã¯ãã³ãžã«ãŸãã¯ççŽ æ°ïŒãïŒã®
ã¢ã«ãã«ïŒ ã®ãšã¹ãã«ãšåŒZNH2ã®ã¢ãã³ãšãåå¿äžæŽ»æ§
ææ©æº¶åªã®ååšäžçŽïŒã110âã®æž©åºŠã§æ¥è§Šã
ããŠåŒ ã®äžéäœãçæãã (b) 該äžéäœãåé¢ãããã®äžéäœãåå¿äžæŽ»æ§
溶åªäžçŽ120ã200âã®æž©åºŠã§å ç±ããããšãã
ãªãæ¹æ³ã«é¢ããã æ¬çºæã®åŒïŒïŒã®ååç©ããã³æ¬çºæã®å·¥çš
äžã眮æåºïŒ²ãR1ããã³ïŒºãšããŠç¹ã«å¥œé©ãªã®
ã¯ã次ã®ãã®ã§ããïŒ ïŒ²ã¯ïŒããïŒåã®ççŽ ååãæããã¢ã«ãã«åº
ã§ããã R1ã¯ãïŒããïŒåã®ççŽ ååãæããã¢ã«ã
ã«åºã§ããã ãããŠïŒºã¯ãïŒâããªãžã«åºãïŒâãã¢ãŸãªã«
åºãïŒâã¡ãã«âïŒâã€ãœããµãŸãªã«åºãïŒâã¡
ãã«âïŒâããªãžã«åºããŸãã¯ïŒïŒïŒâãžã¡ãã«
âïŒâãã¢ãŸãªã«åºã§ããã äžè¿°ã®çœ®æåºãšããŠããã«ç¹ã«å¥œé©ãªã®ã¯æ¬¡ã®
ãã®ã§ããïŒ ïŒ²ã¯ã¡ãã«åºã§ããã R1ã¯ã¡ãã«åºãŸãã¯ãšãã«åºã§ããããã㊠ã¯ãïŒâããªãžã«åºãïŒâãã¢ãŸãªã«åºãŸã
ã¯ïŒâã¡ãã«âïŒâã€ãœããµãŸãªã«åºã§ãããæ¬
çºæã®æã奜é©ãªååç©ã¯ãåŒäžã®ïŒ²ããã³R1
ãåã ã¡ãã«åºã§ãã€ãŠïŒºãïŒâããªãžã«åºã§ã
ããåŒïŒïŒã®ååç©ã§ãããæ¬çºæã®å·¥çšã«ã
ã€ãŠåŸãããçžåœããåŒïŒïŒã®æççå€ã¯ãç·
称çã«ãããã¯ã·ã«ã ïŒpiroxicamïŒããšããŠç¥
ãããŠãããäŸãã°ãã¯ã€ãºãã³ïŒWisemanïŒã
Roy.Soc.Med.Int.Cong.Symp.Ser.ïŒã11â23
ïŒ1978ïŒãåç §ããããã æ¬çºæã®æ¹æ³ã¯ãæ¹è¯ãããåçãšå¢å€§ããã
çç£æ§ãšããå©ç¹ãæãã溶åªã®äœç©ãããããª
ãå€ééã®åŒïŒïŒã®çæç©ãäžãããæ¬çºæã®
å·¥çšã«ãã€ãŠåŸãããåŒïŒïŒã®çæç©ã¯ããŸã
æ¹è¯ãããçŽåºŠããæããŠãããæ¬çºæã®å·¥çšã®
ãã®äžã®å©ç¹ã¯ãæ¯æ¶²ã次ã®ããããžç¹°ãè¿ãå
埪ç°ãããããšãã§ããããã«ãã€ãŠå¥œçµæãåŸ
ãããããšã§ããã æ¬çºæã®å·¥çšã«ãããåŒïŒïŒã®äžéäœã®åé¢
ã«ãã€ãŠãå è¡æè¡ã®å·¥çšã«ãããŠã¯äžå¯èœã§ã
ã€ãä»å çãªç²Ÿè£œãè¡ãªãããšãã§ãããããã
ãŠããã®æ¹æ³ã§ã¯ãäžéäœååç©ïŒïŒã®åé¢ã«
ãã€ãŠç²Ÿè£œããããããããçŽåºŠã®äœãåºçºç©è³ª
ãçšããããšãã§ããããã®ããšã¯ãæççå€
ïŒïŒã®çŽåºŠãäœäžãããããšãªãäžçŽãªã¢ãã³
ZNH2ã䜿çšããããšãã§ãããããæãããªå©
ç¹ã§ãããããã«ãäžã«å®çŸ©ãããããªåŒZNH2
ã®ã¢ãã³ã¯ãå è¡æè¡ã®æ¹æ³ã«ãã€ãŠã¯ç²Ÿè£œãå°
é£ã§ããããšã¯ãåœåéã§å ¬ç¥ã§ããã æ¬çºææ¹æ³ã«ãããã®åŒïŒïŒã®ååç©ã¯ãã»
ãŒçã¢ã«éã®ãåŒïŒïŒã®ïŒâãªããœâïŒïŒïŒâ
ãã³ãŸãã¢ãžã³âïŒâã«ã«ãã³é žãšã¹ãã«ãšé©åœ
ãªã¢ãã³ãZNH2ïŒåŒäžïŒºã¯å ã«å®çŸ©ããéãã§
ããïŒãšãæ¥è§Šãããããšã«ãã€ãŠåŸããããã
ã®åå¿ã¯ãåå¿ã«äžæŽ»æ§ãªææ©æº¶åªã®ååšã«ãã
ãŠã枩床çŽïŒãã110âãããã³åå¿æé24æé
ãŸã§ãã§å®æœãããããã®åå¿ã«å¯Ÿããç¹ã«å¥œé©
ãªæž©åºŠç¯å²ã¯çŽ20ãã90âã§ããããã®æž©åºŠã§
ã¯ããã®åå¿ã¯éåžžæ°åããæ°æéãäŸãã°15å
ããçŽïŒæéã§å®äºããããã®åŸãææãªãã°åŒ
ïŒïŒã®çæç©ã¯ãäŸãã°ããã®åå¿æ··åç©ã宀
æž©ãŸãã¯ãã以äžã«å·åŽããæ²æŸ±ããåºäœãé
ããŠéãããããŠä¹Ÿç¥ãããããšã«ãã€ãŠãåé¢
ãããã ãã®äžã§éå®ãããåå¿ã«äžæŽ»æ§ãªææ©æº¶åª
ã¯ãçšããããåå¿æ¡ä»¶ã§åºçºç©è³ªãŸãã¯åå¿ç
æç©ã®ã©ã¡ããšãç®ã«èŠããã»ã©åå¿ããããã
ãåå¿æž©åºŠãŸãã¯ãã以äžã®æž©åºŠã§ãå°ãªããšã
å®è³ªåã®åºçºç©è³ªã溶解ãããããšãã§ãããã®
ã§ãããããã«ãäžèšã®æº¶åªã¯ãåœæè¡åéã«ç¿
çãã人ã«ã¯å ¬ç¥ã®æšæºçãªæè¡ã«ãã€ãŠææã®
çæç©ããã®æº¶åªãã容æã«ååã§ãããã®ã§ã
ããåŒïŒïŒã®ææã®ååç©ã®è£œé ã«äœ¿çšããåŸ
ããåå¿ã«äžæŽ»æ§ãªææ©æº¶åªã®äŸã¯ããã³ãŒã³ã
ãã«ãšã³ããã·ã¬ã³é¡ããšãã«ãã³ãŒã³ãããã©
ãªã³ããã³ãã«ãªã³ã®ãããªçåæ°ŽçŽ é¡ïŒã¯ãã
ãã«ã ãäºå¡©åã¡ãã¬ã³ãäºå¡©åãšãã¬ã³ãèå
ãšãã«ããã³äºèåãšãã¬ã³ã®ãããªããã²ã³å
çåæ°ŽçŽ é¡ïŒã¢ã»ãã³ããã³ã¡ãã«ãšãã«ã±ãã³
ã®ãããªã±ãã³é¡ïŒãšãã«ãšãŒãã«ãããã©ãã
ããã©ã³ãïŒïŒïŒâãžã¡ããã·ãšã¿ã³ããã³ãžãš
ãã¬ã³ã°ãªã³ãŒã«ãžã¡ãã«ãšãŒãã«ã®ãããªãšãŒ
ãã«é¡ïŒãžã¡ãã«ãã«ã ã¢ããããžã¡ãã«ã¢ã»ã
ã¢ããããã³ïŒ®âã¡ãã«âïŒâãããªãžãã³ã®ã
ããªãžã¢ã«ãã«ã¢ããé¡ïŒãžã¡ãã«ã¹ã«ããã·ã
ããã³ã¢ã»ããããªã«ïŒã§ãããç¹ã«å¥œé©ãªã®
ã¯ãå°ããšããçšããããæé«åå¿æž©åºŠãšåãäœ
é«ã倧æ°æ²žç¹ãæãããäžè¿°ã®æº¶åªã§ãããç¹ã«
奜é©ãªã®ã¯ãçµæžæ§ããã³å¹çã®ãããåçšæ··å
ãã·ã¬ã³ã§ããã åŒïŒïŒã®çæç©ã«é¢ããæåã®ç 究ã§ã¯ãã
ã®ãããªåå¿ã®ããã®å€å žçãªïŒäžå®å®ãªïŒäžé
äœã«é¡äŒŒããæ§é ã圢æããããã®ãã¢ãã³ãšãš
ã¹ãã«ãšã®éã®å ±æçµåã瀺åããããããããª
ãããããã«ç 究ããçµæã¯ãïŒïŒïŒã¢ã«ä»å ç©
ããå®éšåŒïŒïŒã®ååç©ã®æ§é ãããæ£ç¢ºã«è¡š
ãããšã匷ã瀺åããŠããã 13CâNMRããã³
1HâNMRã¹ãã¯ãã«èšŒæ ããã³èµ€å€ã¹ãã¯ã
ã«ã«ãããäºã€ã®ã«ã«ããã«åž¯ã®ååšã¯ãç¹ã«ã
ãã®ãããªä»å ç©ãšäžèŽããŠããã äžè¿°ããããã«ãåŒïŒïŒã®ååç©ã¯ãR1OH
ã®é€å»ã«ããåŒïŒïŒã®æççå€ã®çæã«ããã
äžéäœãšããŠæçšã§ããã äžã®åå¿ããŸããäžã«éå®ãããç¹ã«å¥œé©ãªå
å¿ã«äžæŽ»æ§ãªææ©æº¶åªã®äžã€ã®ååšã«ãããŠå®æœ
ãããããäœãã枩床ã¯ãåå¿äžã«çºçããã¢ã«
ã³ãŒã«ãè¿œãåºãããã«ãé«ãããã枩床ã§å®æœ
ãããããã®åå¿ã«å¥œé©ãªæž©åºŠã¯ãçŽ120ãã200
âã§ãããç¹ã«å¥œé©ãªã®ã¯çŽ135ãã145âã§ã
ãã äžèšåå¿ã«ããåŒïŒïŒã®ååç©ã®çæã«äœ¿çš
ããåŸããåå¿ã«äžæŽ»æ§ãªææ©æº¶åªã¯ã奜é©ãªæž©
床ç¯å²ããå®è³ªçã«äœã枩床ã§æ²žãšãããã®ãã
é«å§è£ 眮ã®äœ¿çšãå¿ èŠãšããã§ããã溶åªãé€ã
ãŠãæ¬çºæã®åŒïŒïŒã®ååç©ã®çæã®ããã«äž
ã«ç€ºãããã®ãšåãã§ããããã®åå¿ã«ç¹ã«é©ã
ã溶åªã¯ãããªãšã³ããã·ã¬ã³é¡ããšãã«ãã³ãŒ
ã³ãããã©ãªã³ããã³ãã«ãªã³ã§ããïŒãããŠæ
ã奜é©ãªã®ã¯ãçµæžæ§ãšå¹çã®ç¹ãããæ··åãã·
ã¬ã³ã§ããããã¡ãããåœåéã«ç¿çãã人ã«èª
ããããéãæ··åãã·ã¬ã³ã¯ã枩床å¶åŸ¡ãšå¯çæ
ç©ã®ã¢ã«ã³ãŒã«ãR1OHã®é€å»ãšã容æã«ããç¹
城ã§ãããç¹ã«å¥œé©ãªæž©åºŠç¯å²å ã®æ²žç¹ãæãã
ãšããå©ç¹ãæããŠããã æ¬çºæã®å·¥çšã®ç¬¬äžæ®µéã«ãããŠã¯ãåŒïŒïŒ
ã®åºäœäžéäœçæç©ã®åœ¢æã¯ããšã¹ãã«ïŒïŒãš
ã¢ãã³ZNH2ãåå¿ãããŠçŽæ¥ïŒïŒã圢æãã
ãå è¡æè¡ã®å·¥çšã§ã¯äžå¯èœãªç²Ÿè£œæ³ãäžããã
ãã®ãããæ¯èŒçäžçŽãªåŒïŒïŒããã³ZNH2ã®
åºçºç©è³ªãããã®æ¹æ³ã«ãããŠã¯äœ¿çšãããããš
ãã§ãããããŠæççå€ïŒïŒã«å€æããåã«ã
æ°èŠãªåŒïŒïŒã®äžéäœãåé¢ããããšã«ãã€ãŠ
粟補ãè¡ãªãããšãã§ããã æ¬çºæã®æ¹æ³ã®ããã«å¥ã®å©ç¹ã¯ãææã®çæ
ç©ïŒïŒãæ¹è¯ãããåçã§ãããããæã奜ãŸ
ããå è¡æè¡æ¹æ³ãããªãã¡ãçžåœããïŒâã«ã«
ãã³é žãšã¹ãã«ãšZNH2ïŒïŒºã¯ãã®äžã§å®çŸ©ãã
éãã§ããïŒã®ãããªè€çŽ ç°åŒã¢ãã³ãçµããã
ã³ãŸãã¢ãžã³âïŒâã«ã«ãããµããã®çæã«ã€ã
ãŠäžè¿°ããç±³åœç¹èš±ç¬¬3591584å·ã®æ¹æ³ã«ã€ããŠ
å¯èœã§ãããããããã«å€§ããªåŠçéã§ãåŸãã
ãããšãã§ããããšã§ãããå è¡æè¡æ³ã«ãããŠ
ã¯ã溶åª100mlãããçŽïŒïœãã倧ããªå šåå¿äœ
æ¿åºŠãçšãããããšããåå¿æ··åç©ã¯æ¯èŒçé«æ°Ž
æºã®å解çæç©ãšçè²äœãçæãããããåŒ
ïŒïŒã®ææçæç©ã®åé¢ãå°é£ã«ãããã以äž
ã®è²»çšã®ããã粟補段éãªãã«ã¯è¬åŠç䜿çšã«é©
ããªãäžçŽãªçæç©ãäžããã ããããªãããæ¬çºæã®å·¥çšã¯ãçæç©ã®åé
ãŸãã¯ãã®çŽåºŠãç ç²ã«ããããšãªããåŠçéã
段é(b)ã«ãããŠ100mlãããïŒâïŒã°ã©ã ãŸãã¯
ãã以äžã«å¢å€§ãããããšã®ã§ãããããªæ¹æ³ã§
å®æœãããããšãã§ãããããã¯æ®µé(a)ã§åŸãã
ãåŒïŒïŒã®æ°èŠãªäžéäœååç©ãåé¢ãããã
ãæ°åã«åããŠã段é(b)ã§çšããããå ç±ããã
溶åªæ··åç©ã«å ããŠãèŠçŽ R1OHãé€å»ãçæç©
ïŒïŒãé«åçããã³é«çŽåºŠã§åœ¢æãããããšã«
ãã€ãŠéæãããã æ¬çºæã®å·¥çšã«ã€ããŠèšŒæãããããšã®ã§ãã
ããã«ããäžã€ã®å©ç¹ã¯ãæ¯æ¶²ã次ã®åå¿æäœã«
ããè¿ãå埪ç°ãããããããšãã§ããããšã§ã
ããæ¬å·¥çšã«ãããŠæ¯æ¶²ãããè¿ãå埪ç°ããã
åŸã«ãé«åçé«çŽåºŠã®çæç©ã芳å¯ãããããã
ãŠæ¯æ¶²äžã«ä¿çãããçæç©ã®æ倱ãé¿ããã
ãããããšå¯Ÿç §çã«ãå埪ç°ãå è¡æè¡å·¥çšã«ã€
ããŠå®æœãããšãã¯äžçŽç©ã®å ç©ããäºã»äžåã®
æ¯æ¶²ã®å埪ç°åŸã«ã¯éåžžã«å€§ãããªã€ãŠãææã®
çæç©ãåé¢ããããšãã§ããªããããããã¯é
åžžãªå°é£ã䌎ãªã€ãŠããåé¢ããããšãã§ããª
ãã 以äžã®å®æœäŸã¯ãç¹èš±è«æ±ãããçºæã説æã
ããã®ã§ãããNMRã®ããŒã¯ã®å€é床ã«å¯ŸããŠ
次ã®çç¥ãçšããããïŒ ïœãåäžç·ïŒïœãäºéç·ïŒïœãäžéç·ïŒïœã®
ïœãäžéç·ã®äºéç·ïŒïœãåéç·ïŒïœãå€éç·ã åèäŸ ïŒ åŒïŒïŒãïŒR1ïŒCH3ãZ1ïŒïŒâããªãžã«åº
ã®çµæ¶æ§ååç© çªçŽ é°å²æ°äžã§ã300mlã®ãã·ã¬ã³äžã®120ïœ
ïŒ0.446ã¢ã«ïŒã®3.4âãžãããâïŒâã¡ãã«âïŒ
âãªããœâ2HâïŒïŒïŒâãã³ãŸãã¢ãžã³âïŒâ
ã«ã«ãã³é žã¡ãã«âïŒïŒïŒâãžãªãã·ãã®æº¶æ¶²
ã«ã48ïœïŒ0.510ã¢ã«ïŒã®ïŒâã¢ããâããªãžã³
ãå ããããã®æ··åç©ããã¯ãããããã¯ãããª
ãã80âã«å ç±ãããã®æž©åºŠã«ïŒæéä¿ã¡å®€æž©ãŸ
ã§å·åŽããéããŠä¹Ÿç¥ããããšãææã®é¯åå
ç©158.6ïœïŒ98ïŒ ïŒããé»è²ã®çµæ¶ãèç¹132â
133âããšããŠåŸãããã è©ŠæããïŒïŒïŒïŒäœç©æ¯ïŒã¡ã¿ããŒã«ïŒæ°Žäžã®
0.50Nã®å¡©é žã§æ»Žå®ãããšãäžååœéã¯367.6ïŒç
è«å€363ïŒã§ãã€ãã質éã¹ãã¯ãã«ïŒïœïŒïœ ïŒ
芪ããŒã¯ã¯331ãèµ€å€ã¹ãã¯ãã«ïŒKBrïŒcm-1ïŒ
1675ããã³1660cm-1ã§åŒ·ãã«ã«ããã«åºã®åžåã åæïŒC16H17N3O5SãšããŠã® èšç®å€ïŒïŒ£ã52.89ïŒïŒšã4.72ïŒïŒ®ã11.56 å®æž¬å€ïŒïŒ£ã52.88ïŒïŒšã4.77ïŒïŒ®ã11.66 250MHz 1HâNMRïŒCDCl3ïŒppmïŒãã«ã¿ïŒïŒ ppm å€é床 ç©å 8.05 ïœ ïŒ 7.88 ïœ ïŒ 7.73 ïœ ïŒ 7.44 ïœã®ïœ ïŒ 6.60 ïœã®ïœ ïŒ 6.52 ïœ ïŒ 3.97 ïœ ïŒ 2.96 ïœ ïŒ 13CâNMRïŒDMSOïŒïŒ ç· ppm å€é床 ïŒ 167988 ïœ ïŒ 158917 ïœ ïŒ 158449 ïœ ïŒ 146076 ïœ ïŒ 137673 ïœ ïŒ 134902 ïœ ïŒ 133005 ïœ ïŒ 132743 ïœ ïŒ 128662 ïœ 10 126557 ïœ 11 123381 ïœ 12 111736 ïœ 13 109330 ïœ 14 108609 ïœ 15 52458 ïœ 16 38489 ïœ ããã·ã¯ãã«ã ïŒpiroxicamïŒãšïŒïŒïŒâãžã
ããâïŒâã¡ãã«âïŒâãªããœâ2HâïŒïŒïŒâ
ãã³ãŸãã¢ãžã³âïŒâã«ã«ãã³é žã¡ãã«ïŒïŒïŒâ
ãžãªãã·ããšã® 13CâNMRã¹ãã¯ãã«ã®æ¯èŒã®
ããã«ãŠã€ããã«ïŒWhippleïŒããªã«ã¬ããã¯ã»
ãã°ããã€ãã¯ã»ã¬ãŸãã³ã¹ïŒOrganic
Magnetic ResonanceïŒã10ã23ïŒ1977ïŒãåç §ã
ãããã ãžã¡ãã«ã¹ã«ããã·ãäžã®äžèšçæç©ã®è©Šæ
ã«ãïŒïŒïŒâãžãããâïŒâã¡ãã«âïŒâãªããœ
â2HâïŒïŒïŒâãã³ãŸãã¢ãžã³âïŒâã«ã«ãã³
é žã¡ãã«ïŒïŒïŒâãžãªãã·ã1.0åœéãæ·»å ãã
ãšã 13CâNMRã¹ãã¯ãã«ã®ç·ã®ãã¡11ãå¢å€§
ããååŠã·ããã¯ãããã«å€åããããã®ããš
ã¯ã溶液äžã§ã¯NMRæéç®çã®éã«ãã°ãã亀
æãããããšãã¯ã€ãã瀺ããŠããã ç·åæã®ããã«ãäžèšã§åŸãããçæç©ã宀
æž©ã§ã¢ã»ãã³ããçµæ¶åãããŠå€§ããªé»è²ç«æ¹äœ
ã®çµæ¶ãåŸããèç¹132âïŒéãïŒ ïŒžç·ããŒã¿ããã次ã®ããšãçµè«ãããã (ã€) ãšããŒã«æ§ãããã³ã¯ïŒâã¢ããããªãžã³ã®
ç°äžã®çªçŽ ããã³ãšã¹ãã«ã«ã«ããã«é žçŽ åå
ã«çµåããæ°ŽçŽ ã§ããããšïŒ (ã) ïŒâã¢ããåºã®ãããã³ã®ãã¡ã®ïŒã€ã¯ãšã
ãŒã«æ§é žçŽ ååã«çµåãããŠããããšïŒ (ã) ä»ã®ïŒâã¢ãããããã³ã¯äžèšçæç©ã®ãã
ïŒã€ã®ååã®ã¹ã«ãã³ã®é žçŽ ååã«çµåããã
æ°ŽçŽ ã§ããããšïŒ (ã) äžèšçæç©ã®æ§é ã¯äžèšåŒã«ãã€ãŠè¡šããã
ãïŒ ïŒåŒãïŒR1ïŒCH3ãZ1ã¯ïŒâããªãžã«ç°
ãå®æããïŒ åèäŸ ïŒ 13mlã®ã¢ã»ãã³ã«ã2.69ïœïŒ0.01ã¢ã«ïŒã®ïŒïŒ
ïŒâãžãããâïŒâã¡ãã«âïŒâãªããœâ2Hâ
ïŒïŒïŒâãã³ãŸãã¢ãžã³âïŒâã«ã«ãã³é žã¡ãã«
ïŒïŒïŒâãžãªãã·ãããã³0.94ïœïŒ0.01ã¢ã«ïŒã®
ïŒâã¢ããããªãžã³ãå ããæ··åç©ãæž©ããŠæº¶æ¶²
ãšããããã®é»è²ã®æº¶æ¶²ããæ²æŸ±ãå®äºãããŸã§
å·èµããŠãéããé»è²ã®çµæ¶ã也ç¥ãããŠãå
åç©ïŒïŒãïŒR1ïŒCH3ãïŒïŒâããªãžã«
åºãèç¹132â133âã84ïŒ ã®åçã§åŸãã äžèšã®å·¥çšããåãèŠæš¡ã§ãã¢ã»ãã³ã®ä»£ãã«
çš®ã ã®åå¿ã«äžæŽ»æ§ãªææ©æº¶åªãçšããŠãããè¿
ãããã®çµæãäžã®è¡šã«èŠçŽããã ãè¡šã ãã«æž©
ãã
ãè¡šã ããŠæ²æŸ±ã
ãã
äžã®åå¿ãã溶åªãšããŠã®ã¢ã»ãã³äžã§ããã
ïŒã¢ã«éå°ã®ã¡ãã«ãšã¹ãã«ãŸãã¯ïŒâã¢ããã
ãªãžã³åå¿äœãçšããŠããè¿ããšãã¯ãåãçæ
ç©ãé»è²çµæ¶ãèç¹132â134âãšããŠåŸãããã
ãšã¹ãã«åå¿äœïŒïŒãéå°ã«çšãããšãããã
ã¯æã«ã¯ãã©ã¹ã³ã®åŽé¢ã«ä»çããçœè²åºäœãšã
ãŠããããããã®ãã®ã¯åŒïŒïŒã®é»è²çµæ¶ãã
容æã«åé¢ãããã ãã®å·¥çšãïŒâã®ããã©ããããã©ã³äžãŸãã¯
110âã®ãã«ãšã³äžã§ããè¿ããšããçµæã¯å®è³ª
äžåäžã§ããã åèäŸ ïŒ ïŒïŒïŒâãžãããâïŒâã¡ãã«âïŒâãªããœâ
2HâïŒïŒïŒâãã³ãŸãã¢ãžã³âïŒâã«ã«ãã³é ž
ã¡ãã«ïŒïŒïŒâãžãªãã·ããé©åœãªåŒïŒïŒã®å
åç©ã§çœ®ãæããŠãåèäŸïŒãŸãã¯ïŒã®å·¥çšãã
ãè¿ããšããçžåœããããïŒâããªãžã«åºã§ã
ãåŒïŒïŒã®ååç©ãåŸãããã  R1 CH3 C2H5 CH3 ïœâC3H7 C2H5 ïœâC3H7 C6H5CH2 ïœâC4H9 CH3 ïœâC4H9 ïœâC3H7 ïœâC4H9 ïœâC3H7 secâC4H9 C6H5CH2 CH3  ïœâC4H9  C2H5 åèäŸ ïŒ åŒïŒïŒãïŒR1ïŒCH3ãïŒïŒâãã¢ãŸãªã«
åºãã®çµæ¶æ§ååç© çªçŽ äžã§ããã¯ããããïŒïŒïŒâãžãããâïŒ
âã¡ãã«âïŒâãªããœâ2HâïŒïŒïŒâãã³ãŸã
ã¢ãžã³âïŒâã«ã«ãã³é žã¡ãã«ïŒïŒïŒâãžãªãã·
ã2.69ïœïŒ10ããªã¢ã«ïŒãšãã·ã¬ã³50mlãšã®æ··å
ç©ã«ã1.05ïœïŒ10.5ããªã¢ã«ïŒã®ïŒâã¢ãããã¢
ãŸãŒã«ãå ããããã®æ··åç©ãïŒæé85â90âã«
å ç±ãã宀枩ãŸã§å·åŽããŠéããããŠè€è²ã®çµ
æ¶æ§çæç©ãç空也ç¥ãããŠè¡šé¡ååç©2.3ïœ
ïŒ62.3ïŒ ïŒãèç¹131â141âãåŸãã ãã®çµæ¶çæç©ã20mlã®å¡©åã¡ãã¬ã³ã«æº¶è§£ã
ãã掻æ§çãå ããŠè±è²ããåŸéããããã®
液ãååã«ããã¯ãããªãããããµã³ã«æ·»å ãïŒ
æéç²ç ãããã®åŸéãããšçœè²çµæ¶çæç©ïŒ
èç¹140ã145âãã1.35ïœåŸãããã 溶åªãšããŠã¢ã»ãã³ãå¡©åã¡ãã¬ã³ããšãã«ãš
ãŒãã«ãäºèåãšãã¬ã³ãïŒïŒïŒâãžã¡ããã·ãš
ã¿ã³ããã³ãŒã³ããžã¡ãã«ãã«ã ã¢ããããžã¡ã
ã«ã¢ã»ãã¢ããããšãã«ãã³ãŒã³ããã«ãšã³ãŸã
ã¯ãã«ãªã³ãçšããŠæž©åºŠïŒâ110âã§ïŒâ24æéã
äžèšå·¥çšãããè¿ããšããåŒïŒïŒã®ææã®çæ
ç©ãåæ§ã«åŸãããã åèäŸ ïŒ é©åœãªãåŒïŒïŒããã³ZNH2ã®åºçºç©è³ªãçš
ããããšã«ãã€ãŠãåèäŸïŒâïŒã®å·¥çšã«ãã€ãŠ
次ã®åŒïŒïŒã®ååç©ãåŸãããã ãè¡šã ãè¡šã ãžã«
ãè¡šã ãè¡šã ãã¢ãŸãªã«
åèäŸ ïŒ ããã¯ã·ã«ã ã®æšæºç補é æ³ æž©åºŠèšãå å¡«èžçå¡ãå·åŽæ©ããã³ããã¯ãæ©
ããšãã€ããïŒãªããã«ãã©ã¹ã³ã«ãçªçŽ ç²å²æ°
äžã§ãæ··åãã·ã¬ã³3300mlãïŒïŒïŒâãžãããâ
ïŒâã¡ãã«âïŒâãªããœâ2HâïŒïŒïŒâãã³ãŸ
ãã¢ãžã³âïŒâã«ã«ãã³é žã¡ãã«ïŒïŒïŒâãžãªã
ã·ã80ïœïŒ0.297ã¢ã«ïŒãïŒâã¢ããããªãžã³32ïœ
ïŒ0.340ã¢ã«ïŒããã³æŽ»æ§çïŒDarco â60â»ãŸ
ãã¯Darco KBBâ»ïŒïŒïœãå ããããã®æ··åç©
ã28æéå ç±éæµïŒçŽ140âïŒããããããã®éã
æåã®ïŒæéã¯æ¯æçŽ25mlã®é床ã§ãã®åŸæ®ãã®
éæµæéã¯æ¯æïŒâ10mlã®é床ã§ãã¡ã¿ããŒã«ãš
ãã·ã¬ã³ãšãèžçããŠé€ããäžæ¹ã§æ°ãããã·ã¬
ã³ãå ããŠåå¿ç©ã®å®¹ç©ãçŽ3500mlã«ä¿ã€ã28æ
éåŸã«ããã®åå¿æ··åç©ãå°ãå·åŽãïŒã100
âïŒãéããŠççŽ ãé€å»ããããã®ççŽ ã±ãŒã
ãæž©ãã·ã¬ã³ïŒ100mlïŒã§æŽæµãã液ãšæŽæµæ¶²
ãè¿ éã«ããããããªããçªçŽ é°å²æ°äžã§25â50
âãŸã§ãã€ããå·åŽãããå®å šã«çµæ¶åãããã
ãã«ãïŒæéããã¯ããç¶ãããçµæ¶ãéã«ã
ã€ãŠéããæ¯æ¶²ãçŽ1500mlãŸã§æ¿çž®ããçªçŽ äžã§
ïŒâïŒâã«å·åŽããéããŠããã®ã±ãŒãã100
mlã®å·ãã·ã¬ã³ã§æŽæµãããããŠçµæ¶ãç空äž60
â以äžã§æ°æé也ç¥ããããåéã¯ã76.7â84.6
ïœïŒçè«éã®78â86ïŒ ïŒã§ãããå¹³ååŠçé24.4
ïœïŒæº¶åªã â»ã¢ã€ã»ã·ãŒã»ã¢ã€ã»ã¢ã¡ãªã«ç€Ÿ ïŒICIAmericaãInc.ïŒã®ç»é²åæš å®æœäŸ ïŒ äžéäœïŒïŒ©ãïŒR1ïŒCH3ãïŒïŒâããªãž
ã«åºïŒãçšããæ¹è¯ãããããã¯ã·ã«ã æ³ ïŒ¡ çªçŽ ã§ããŒãžããïŒãªããã«ãã©ã¹ã³ã«ãæ··
åãã·ã¬ã³300mlãïŒïŒïŒâãžãããâïŒâã¡
ãã«âïŒâãªããœâ2HâïŒïŒïŒâãã³ãŸãã¢
ãžã³âïŒâã«ã«ãã³é žã¡ãã«ïŒïŒïŒâãžãªãã·
ã120ïœïŒ0.446ã¢ã«ïŒããã³ïŒâã¢ããããªãž
ã³48ïœïŒ0.510ã¢ã«ïŒãå ããããã®æ··åç©ã
90âã«å ç±ãããã®æž©åºŠã§ïŒæéè¿ éã«ããã¯
ãããŠãããçªçŽ é°å²æ°äžã§å·åŽãããã 3300mlã®ãã·ã¬ã³ãå«æããïŒãªããã«ãã©
ã¹ã³ã«ã12ïœã®æŽ»æ§çïŒDarco â60ïŒãå
ãããã®æ··åç©ãå ç±éæµããããã®éã«åé¢
åšïŒãã«ã³ã¿ãŒäžã«ãã·ã¬ã³ïŒæ°Žãéãããã
ã®ãã®ã«ãäžã§åŸãäžèšã®åŒïŒïŒã®äžéäœå
åç©ã®ãã·ã¬ã³ã¹ã©ãªãŒã®ååãå ããããã®
æ··åç©ãéæµãããŠãã¡ã¿ããŒã«ïŒãã·ã¬ã³ã
æ¯æ25mlã®é床ã§èžçããŠé€ãããäžæ¹ã§æ°ã
ããã·ã¬ã³ãå ããŠåå¿äœç©ãçŽ3500mlã«ä¿æ
ãããïŒæéåŸã«ãæ®çããäžéäœååç©ã®ã¹
ã©ãªãŒã®ïŒåã®ïŒãå ããåãé床ã§ã¡ã¿ããŒ
ã«ïŒãã·ã¬ã³ã®èžçãç¶è¡ãããäžéäœã®æ®ç
éšïŒïŒåã®ïŒãŸãã¯æ®éšïŒãïŒæéããã³12æ
éã§åã å ãããããŠèžçã25mlïŒæã§ãå šäœ
ã§16æéç¶ããã16æéåŸã«ãèžçæ·»å ãæ¯æ
12.5mlã«äžããŠå šäœã§34æéç¶ããã åå¿æ··åç©ãçŽ100âãŸã§å·åŽããŠãéã
ãŠççŽ ãé€å»ãããã®ççŽ ã±ãŒãã100mlã®æž©
ãã·ã¬ã³ã§æŽæµããã液ãçªçŽ ã§ããŒãžã
ãŠãè¿ éã«ããã¯ãŒããªãã25â50âã«å·åŽã
ããå®å šã«çµæ¶ããããã«ïŒæéããã¯ããç¶
ããããã®çµæ¶ãéã«ãã€ãŠéããæ¯æ¶²ãæ¿
çž®ããŠçŽ1500mlãšããçªçŽ äžã§ïŒâïŒâã«å·åŽ
ããŠéããã±ãŒãã100mlã®å·ãã·ã¬ã³ã§æŽ
æµãããããŠçµæ¶æ§çæç©ã60â以äžã§ç空也
ç¥ããããããã¯ã·ã«ã ã®åéã¯ã121â132.8
ïœïŒçè«ã®82â90ïŒ ïŒã§ãããå¹³ååŠçé38.5
ïœïŒæº¶åªã  次ã®ããã«å€åœ¢ããŠäžèšå·¥çšãããè¿ãïŒçª
çŽ é°å²æ°äžã§ãæ··åãã·ã¬ã³600mlã«ã160ïœ
ïŒ0.594ã¢ã«ïŒã®ïŒïŒïŒâãžãããâïŒâã¡ãã«
âïŒâãªããœâ2HâïŒïŒïŒâãã³ãŸãã¢ãžã³
âïŒâã«ã«ãã³é žã¡ãã«ïŒïŒïŒâãžãªãã·ããš
60ïœïŒ0.637ã¢ã«ïŒã®å·¥æ¥éæã®ïŒâã¢ããã
ãªãžã³ãå ãããæ··åç©ãïŒæéã85â90âã«
å ç±ãã20â25âã«å·åŽãããã®æž©åºŠã§ïŒæé
ããã¯ããããããããŠåŸãããçµæ¶æ§äžéäœ
ãéã«ãã€ãŠéããŠã100mlã®å·ãã·ã¬ã³ã§
æŽæµããã秀éãã溶åªã§æ¹¿ã€ãçµæ¶ã®è©Šæã
ç空也ç¥ãããã也ç¥è©Šæã®å·®åèµ°æ»ç±é枬å®
ã¯132.9âã§åäžã®éãããŒã¯ã瀺ããã也ç¥
ããè©Šéã®ééãããåŒïŒïŒãïŒR1ïŒ
CH3ãïŒïŒâããªãžã«åºãã®äžéäœã®åéã
215.9ïœïŒ98ïŒ ïŒã§ããããšã決å®ãããã 3300mlã®æ··åãã·ã¬ã³ã«ãïŒïœã®ïŒâã¢ãã
ããªãžã³ãïŒïœã®æŽ»æ§çïŒDarco KBBïŒãå
ããç³»ã«æ°ŽåããªããªããŸã§æ··åç©ãå ç±ããŠ
éãã«éæµãããã®éã«ãã·ã¬ã³ïŒæ°Žãéã
ãããã®åŸ50mlã®ãã·ã¬ã³ãšæ··åããäžèšçµæ¶
æ§äžéäœ81ïœïŒä¹Ÿç¥ééåºæºïŒïŒ0.223ã¢ã«ïŒã
å ãããåå¿æ··åç©ãå ç±éæµãããŠã25mlïŒ
æã®é床ã§ã¡ã¿ããŒã«ïŒãã·ã¬ã³ãåé¢ããã
äžã§åŸã215.9ïœãå šãŠæ¶è²»ããããŸã§ïŒæé
æ¯ã«è¿œå ã®17ïœã®äžéäœãå ãããããã«ã¯çŽ
16æéãèŠããã20æéã«éãããŸã§25mlïŒæ
ã§ã®éæµãç¶ãããã®ãšãã«éæµé床ã12â13
mlïŒæã«äžãããå¿ èŠã«å¿ããŠãã·ã¬ã³ãæ·»å
ããããšã«ãã€ãŠãå šåå¿å®¹ç©ã3.3ãªããã«
ãš3.7ãªããã«ãšã®éã«ä¿ã€ãå šåå¿æé34æ
éåŸã«ãæ··åç©ãå·åŽããçæç©ãäžã®ïŒ¡éšã®
ããã«åé¢ãããšã165.3ïœïŒ84ïŒ ïŒã®ããã¯
ã·ã«ã ãåŸããããåŠçé50ïœïŒæº¶åªãªãã
ã«ã æ¯èŒäŸ æ¯æ¶²ã®å埪ç°ãçšãããæšæºããã¯ã·ã«ã æ³ãš
æ¹è¯ããã¯ã·ã«ã æ³ãšã®æ¯èŒ æšæºæ³ïŒåèäŸïŒïŒããã³æ¹è¯æ³ïŒå®æœäŸïŒïŒ
ãã第ïŒã第ïŒããã³ç¬¬ïŒæäœã®åã ã«ãããŠã
åã®æäœããã®æ¯æ¶²ãå埪ç°ãããŠãåã ïŒåã
ãè¿ãããçµæãäžã«èŠçŽããã ãè¡šã äœã®å¹³å
ãã®å埪ç°å®éšã®å段éã§ãæšæºæ³ãçšããã
ããã¯ããé«ãè²æ°Žæºãæããããã¯æŒžé²çã«ã
ãã«ã¯ã€ãããšããŠãããæšæºæ³ã«ãã第ïŒæäœ
ã§ã¯ãçµæ¶åãã²ããããããããšã®ã§ããªãã·
ãããã®ã¿ãåŸãããããããæ¯ã¹ãŠãæ¹è¯æ³ã§
ã¯ç¬¬ïŒæäœã§93ïŒ ã®åçãåŸããæšæºæ³ã§ã¯çæ
ç©ãåŸãããªãã€ãã®ã§ããã®å®éšã¯ãã®æç¹ã§
åæ¢ãããæ¹è¯æ³ã«ããã°ç¬¬ïŒæäœåŸã«ãæ¯æ¶²ã¯
ãŸã éæã§ããããããŠä»®ã«è¡ãªããããšãã
ã°ãããªãæå©ã«ããã以äžã®æäœã«äœ¿çšããã
ããšãã§ããã§ãããã å®æœäŸ ïŒ äžéäœãšããŠãåèäŸïŒã§è£œé ãããé©åœãªåŒ
ïŒïŒã®ååç©ãçšããŠãå®æœäŸïŒããã³æ¯èŒäŸ
ã®å·¥çšãããè¿ããšãã次ã®åŒïŒïŒã®çæç©ã
ãŸãæ¹è¯ãããåçããã³åŠçéã§åŸãããã åŒäžïŒ²ããã³R1ã¯åèäŸïŒã§å®çŸ©ããéãã§
ããã å®æœäŸ ïŒ å®æœäŸïŒã®å·¥çšããã³æ¯èŒäŸã®å埪ç°å·¥çšã§ã
åºçºç©è³ªãšããŠåèäŸïŒããã³ïŒã§è£œé ãããåŒ
ïŒïŒã®ååç©ãçšãããšã以äžã®åŒïŒïŒã®ç
æç©ããŸãæ¹è¯ãããåçããã³åŠçéã§åŸãã
ãã åŒäžãããã³ïŒºã¯ãåèäŸïŒããã³ïŒã§å®çŸ©
ããéãã§ããã å®æœäŸ ïŒ äžéäœïŒãïŒR1ïŒCH3ãïŒïŒâãã¢ãŸ
ãªã«åºïŒãçšããæ¹è¯ã¹ããã·ã«ã
ïŒSudoxicamïŒæ³ ãã·ã¬ã³30mlãšãå ã«åŸãåŒïŒïŒã®çµæ¶æ§ïŒ
âãã¢ãŸãªã«äžéäœ0.5ïœãšãå«æãããã©ã¹ã³
ãã2.5æéãããïŒmlã®é床ã§ãã€ããèžçã
ããããããããã·ã¬ã³ïŒïŒmlïŒãšäžéäœ0.25ïœ
ãå ããäžã®ããã«èžçãããè¿ããããã«ãã
äžåºŠãããããè¿ããåŸãæ··åç©ãå šäœã§ïŒæé
ç°æµãããããã®åŸæ··åç©ãé±æ«äžïŒã60æéïŒã
åšå²æž©åºŠã§ããã¯ãããéããŠãããã¯ã·ã«ã
ã®ïŒâãã¢ãŸãªã«åæäœã§ãããçæç©ã¹ããã·
ã«ã ïŒSudoxicamïŒã65ïŒ åçïŒ590mgïŒãèç¹
245â247âïŒå解ïŒããé€å»ããã
Claims (1)
- ãç¹èš±è«æ±ã®ç¯å²ã ïŒ æ¬¡åŒã®ïŒïŒïŒâãžãããâ2HâïŒïŒïŒâã
ã³ãŸãã¢ãžã³âïŒâã«ã«ãããµããâïŒïŒïŒâãž
ãªãã·ãïŒ ïŒåŒäžãã¯æ°ŽçŽ ããã³ãžã«ãŸãã¯ççŽ æ°ïŒãïŒ
ã®ã¢ã«ãã«ïŒïŒºã¯ïŒâããªãžã«ãã¢ã«ãã«çœ®æâ
ïŒâããªãžã«ãïŒâãã¢ãŸãªã«ãïŒåãŸãã¯ïŒå
ã®ã¢ã«ãã«åºã§çœ®æãããïŒâãã¢ãŸãªã«ããã
ãã¯ïŒâã¢ã«ãã«âïŒâã€ãœããµãŸãªã«ã§ããã
ããã§åã¢ã«ãã«ã¯ççŽ æ°ïŒãïŒã§ããïŒ ã®è£œæ³ã§ãã€ãŠãäžèšå·¥çš (a) åŒ ïŒåŒäžãR1ã¯ãã³ãžã«ãŸãã¯ççŽ æ°ïŒãïŒã®
ã¢ã«ãã«ïŒ ã®ãšã¹ãã«ãšåŒZNH2ã®ã¢ãã³ãšãåå¿äžæŽ»æ§
ææ©æº¶åªã®ååšäžçŽïŒã110âã®æž©åºŠã§æ¥è§Šã
ããŠåŒ ïŒZ1ã¯âïŒïŒ®âãšãã€ããã«ãªã€ãŠïŒºã圢æ
ãããïŒ ã®äžéäœãçæãã (b) 該äžéäœãåé¢ãããã®äžéäœãåå¿äžæŽ»æ§
溶åªäžçŽ120ã200âã®æž©åºŠã§å ç±ããããšãã
ãªãæ¹æ³ã ïŒ ïŒ²ãã¡ãã«ã§R1ãã¡ãã«ãŸãã¯ãšãã«ã§ã
ãç¹èš±è«æ±ã®ç¯å²ç¬¬ïŒé ã®æ¹æ³ã ïŒ ïŒºãïŒâããªãžã«ãïŒâãã¢ãŸãªã«ãïŒâã¡
ãã«âïŒâã€ãœããµãŸãªã«ãïŒâã¡ãã«âïŒâã
ãªãžã«ãŸãã¯ïŒïŒïŒâãžã¡ãã«âïŒâãã¢ãŸãªã«
ã§ããç¹èš±è«æ±ã®ç¯å²ç¬¬ïŒé ã®æ¹æ³ã ïŒ ïŒºãïŒâããªãžã«ã§R1ãã¡ãã«ã§ããç¹èš±
è«æ±ã®ç¯å²ç¬¬ïŒé ã®æ¹æ³ã ïŒ å·¥çš(a)ã«ãããŠè©²åå¿ã20â90âã§è¡ãªãã
ãç¹èš±è«æ±ã®ç¯å²ç¬¬ïŒé ã®æ¹æ³ã ïŒ å·¥çš(b)ã«ãããŠæž©åºŠãçŽ135â145âã§ããç¹
èš±è«æ±ã®ç¯å²ç¬¬ïŒé èšèŒã®æ¹æ³ã ïŒ å·¥çš(b)ã®çæç©ãåé¢ãããæ¯æ¶²ã¯å埪ç°ã
ããç¹èš±è«æ±ã®ç¯å²ç¬¬ïŒé ã®æ¹æ³ã ïŒ åå¿äžæŽ»æ§ææ©æº¶åªããã·ã¬ã³ã§ããç¹èš±è«
æ±ã®ç¯å²ç¬¬ïŒé ã®æ¹æ³ã ïŒ å·¥æ¥éæã®ã¢ãã³ZNH2ã䜿çšãããç¹èš±è«
æ±ã®ç¯å²ç¬¬ïŒé ã®æ¹æ³ã ïŒïŒ ãïŒâããªãžã«ã§ããç¹èš±è«æ±ã®ç¯å²ç¬¬
ïŒé ã®æ¹æ³ã ïŒïŒ çµæ¶æ§äžéäœãåé¢ãããç¹èš±è«æ±ã®ç¯å²
第ïŒïŒé ã®æ¹æ³ã
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US28939081A | 1981-08-03 | 1981-08-03 | |
US289390 | 1981-08-03 | ||
US389119 | 1982-06-17 |
Publications (2)
Publication Number | Publication Date |
---|---|
JPS5843969A JPS5843969A (ja) | 1983-03-14 |
JPH0133104B2 true JPH0133104B2 (ja) | 1989-07-11 |
Family
ID=23111335
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP57132922A Granted JPS5843969A (ja) | 1981-08-03 | 1982-07-29 | ãã³ãŸãã¢ãžã³ã«ã«ãããµããé¡ã®è£œé æ¹æ³ |
Country Status (6)
Country | Link |
---|---|
US (1) | US4536573A (ja) |
JP (1) | JPS5843969A (ja) |
CS (1) | CS235955B2 (ja) |
GT (1) | GT198276334A (ja) |
PL (2) | PL134997B1 (ja) |
ZA (1) | ZA825559B (ja) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1707352A1 (en) | 2005-03-31 | 2006-10-04 | Fuji Photo Film Co., Ltd. | Method of producing a planographic printing plate |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
IT1194522B (it) * | 1983-12-16 | 1988-09-22 | Prodotti Antibiotici Spa | Metodo di sintesi di derivanti benzotiazinici |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3591584A (en) * | 1968-08-27 | 1971-07-06 | Pfizer | Benzothiazine dioxides |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3853862A (en) * | 1973-04-23 | 1974-12-10 | Pfizer | Production of 4-hydroxy-1,2-benzothiazine-3-carboxamides |
US3891637A (en) * | 1974-10-01 | 1975-06-24 | Pfizer | Process for the production of carboxamides of oxo-1,2-benzothiazine-1,1-dioxides |
US4289879A (en) * | 1980-09-29 | 1981-09-15 | Pfizer Inc. | Synthetic method and intermediate for piroxicam |
US4309427A (en) * | 1981-01-15 | 1982-01-05 | Pfizer Inc. | Benzothiazine dioxide derivatives |
-
1982
- 1982-07-19 GT GT198276334A patent/GT198276334A/es unknown
- 1982-07-29 PL PL1982244410A patent/PL134997B1/pl unknown
- 1982-07-29 JP JP57132922A patent/JPS5843969A/ja active Granted
- 1982-07-29 PL PL1982237694A patent/PL133808B1/pl unknown
- 1982-07-29 CS CS825724A patent/CS235955B2/cs unknown
- 1982-08-02 ZA ZA825559A patent/ZA825559B/xx unknown
-
1984
- 1984-05-11 US US06/609,126 patent/US4536573A/en not_active Expired - Lifetime
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3591584A (en) * | 1968-08-27 | 1971-07-06 | Pfizer | Benzothiazine dioxides |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1707352A1 (en) | 2005-03-31 | 2006-10-04 | Fuji Photo Film Co., Ltd. | Method of producing a planographic printing plate |
Also Published As
Publication number | Publication date |
---|---|
JPS5843969A (ja) | 1983-03-14 |
PL134997B1 (en) | 1985-09-30 |
ZA825559B (en) | 1983-06-29 |
US4536573A (en) | 1985-08-20 |
GT198276334A (es) | 1984-01-10 |
PL133808B1 (en) | 1985-06-29 |
CS235955B2 (en) | 1985-05-15 |
PL237694A1 (en) | 1983-03-28 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN111303075A (zh) | è¯å¹¶å»åªé ®è¡çç©åå ¶å¶å€æ¹æ³äžäœäžºæç»æ žè¯ç©çåºçš | |
EP0304941B1 (en) | Pharmaceutically useful polymorphic modification of buspirone | |
US3960856A (en) | Process for the preparation of 4-hydroxy-3-(5-methyl-3-isoxazolylcarbamoyl)-2-methyl-2H-1,2-benzothiazine 1,1-dioxide | |
JPH0133104B2 (ja) | ||
JPH0225904B2 (ja) | ||
JP2702519B2 (ja) | å€åœ¢çµæ¶åœ¢æ ã®è»¢ææ³ | |
JP2668816B2 (ja) | ãã³ãŸãã¢ãžã¢ãŸãŒã«èªå°äœã®è£œæ³ | |
JPH0136462B2 (ja) | ||
US4469866A (en) | Intermediates for production of benzothiazine carboxamides | |
JPH0546356B2 (ja) | ||
JP2685120B2 (ja) | ãžãã¢ãŸãªãŠã å¡©ã®è£œé æ¹æ³ | |
JP4425366B2 (ja) | âãã³ãžã«âïŒâããããã·ã¢ãŒããžã³ã®è£œé æ³ | |
US4024136A (en) | Process for the preparation of 4-hydroxy-3-(5-methyl-3-isoxazolylcarbamoyl)-2-methyl-2H-1,2-benzothiazine 1,1-dioxide | |
WO2004089904A2 (en) | Preparation of torasemide | |
EP0076643B1 (en) | Processes for preparing piroxicam and intermediates leading thereto | |
KR810000116B1 (ko) | ìì ì ë첎ì ì ì¡°ë°©ë² | |
JPH0525876B2 (ja) | ||
JPH075554B2 (ja) | ïŒâããã¢ããªãã³âïŒâã«ã«ãããµããååç©ã®è£œæ³ | |
CS235989B2 (cs) | Způsob vÜroby 4-oxo-1^-benzothiazin-3-karboxanfiS-1,1-dioxidů | |
JPH03112966A (ja) | ïŒâã¢ã«ãã«âïŒïŒïŒâãžã¢ããããªãžã³ã®è£œé æ³ | |
JPH0314824B2 (ja) | ||
JPS61118376A (ja) | ïŒâã¡ãã«âïŒâããããã·âïŒïœâïŒïŒïŒâãã³ãŸãã¢ãžã³âïŒïŒïŒïŒâãžãªããµã€ãâïŒâïŒïœâïŒâããªãžã«ïŒâã«ã«ããã·ã¢ããã®è£œæ³ | |
JPS589106B2 (ja) | ãã¯ãœã«ã³ã·ãã«ãŽãŠãããã»ã€ã㊠| |
JPS61204189A (ja) | æ°èŠãªããã ç°ãæããååç©ã®è£œé æ³ | |
JPH032156B2 (ja) |