JPH01254687A - 3-cephem derivative borofluoride-hydroborofluoride - Google Patents
3-cephem derivative borofluoride-hydroborofluorideInfo
- Publication number
- JPH01254687A JPH01254687A JP8278188A JP8278188A JPH01254687A JP H01254687 A JPH01254687 A JP H01254687A JP 8278188 A JP8278188 A JP 8278188A JP 8278188 A JP8278188 A JP 8278188A JP H01254687 A JPH01254687 A JP H01254687A
- Authority
- JP
- Japan
- Prior art keywords
- formula
- compound
- borofluoride
- cephem
- hydroborofluoride
- 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.)
- Granted
Links
- FZEVMBJWXHDLDB-ZCFIWIBFSA-N (6r)-5-thia-1-azabicyclo[4.2.0]oct-2-en-8-one Chemical class S1CC=CN2C(=O)C[C@H]21 FZEVMBJWXHDLDB-ZCFIWIBFSA-N 0.000 title 1
- 239000002253 acid Substances 0.000 claims abstract description 5
- 150000003839 salts Chemical class 0.000 claims abstract description 5
- -1 p-methoxybenzyl ester Chemical class 0.000 claims description 4
- 239000005973 Carvone Substances 0.000 claims 1
- 239000000126 substance Substances 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 abstract description 31
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 abstract description 18
- 238000006243 chemical reaction Methods 0.000 abstract description 5
- 238000001816 cooling Methods 0.000 abstract description 4
- 239000000243 solution Substances 0.000 abstract description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 abstract description 2
- 239000007864 aqueous solution Substances 0.000 abstract description 2
- 101100536354 Drosophila melanogaster tant gene Proteins 0.000 abstract 1
- 239000004599 antimicrobial Substances 0.000 abstract 1
- 239000000463 material Substances 0.000 abstract 1
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 abstract 1
- 238000002360 preparation method Methods 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- 210000002784 stomach Anatomy 0.000 description 9
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 7
- 229910052739 hydrogen Inorganic materials 0.000 description 6
- 150000001782 cephems Chemical group 0.000 description 5
- 238000001914 filtration Methods 0.000 description 4
- 125000002971 oxazolyl group Chemical group 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 229940126062 Compound A Drugs 0.000 description 2
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 2
- KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 2
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 125000006239 protecting group Chemical group 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 150000003952 β-lactams Chemical class 0.000 description 2
- NDVMCQUOSYOQMZ-UHFFFAOYSA-N 2,2-bis(trimethylsilyl)acetamide Chemical compound C[Si](C)(C)C(C(N)=O)[Si](C)(C)C NDVMCQUOSYOQMZ-UHFFFAOYSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- RILZRCJGXSFXNE-UHFFFAOYSA-N 2-[4-(trifluoromethoxy)phenyl]ethanol Chemical compound OCCC1=CC=C(OC(F)(F)F)C=C1 RILZRCJGXSFXNE-UHFFFAOYSA-N 0.000 description 1
- YSUIQYOGTINQIN-UZFYAQMZSA-N 2-amino-9-[(1S,6R,8R,9S,10R,15R,17R,18R)-8-(6-aminopurin-9-yl)-9,18-difluoro-3,12-dihydroxy-3,12-bis(sulfanylidene)-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-1H-purin-6-one Chemical compound NC1=NC2=C(N=CN2[C@@H]2O[C@@H]3COP(S)(=O)O[C@@H]4[C@@H](COP(S)(=O)O[C@@H]2[C@@H]3F)O[C@H]([C@H]4F)N2C=NC3=C2N=CN=C3N)C(=O)N1 YSUIQYOGTINQIN-UZFYAQMZSA-N 0.000 description 1
- PKPGSMOHYWOGJR-UHFFFAOYSA-N 2-methoxyimino-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetic acid Chemical compound CON=C(C(O)=O)C1=CSC(NC(C=2C=CC=CC=2)(C=2C=CC=CC=2)C=2C=CC=CC=2)=N1 PKPGSMOHYWOGJR-UHFFFAOYSA-N 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 241000269821 Scombridae Species 0.000 description 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical group C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hcl hcl Chemical compound Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 235000020640 mackerel Nutrition 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
- 238000000634 powder X-ray diffraction Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- LEMQFBIYMVUIIG-UHFFFAOYSA-N trifluoroborane;hydrofluoride Chemical compound F.FB(F)F LEMQFBIYMVUIIG-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Cephalosporin Compounds (AREA)
Abstract
Description
【発明の詳細な説明】
〈産業上の利用分野〉
本発明は式（１）
で表わされる７β−アミノ−３−［４−（オキサゾール
−５−イル）−１−ピリジニオコメチル−３−セフェム
−４−カルボン酸ｐ−メトキシベンジルエステルホウフ
ッ化物・ホウフッ化水素酸塩及びその水和物に関する。Detailed Description of the Invention <Industrial Application Field> The present invention relates to 7β-amino-3-[4-(oxazol-5-yl)-1-pyridiniocomethyl-3- The present invention relates to cephem-4-carboxylic acid p-methoxybenzyl ester borofluoride/hydroboric acid salt and its hydrate.
式（りの化合物は、抗菌剤として優れた下記式（！Ｉ）
の化合物（特開昭８０−２２２４９０号公報参照）の製
造中間体として有用なものである。The compound of the formula (R) is useful as an intermediate for the production of the compound of the following formula (!I) (see JP-A-80-222490), which is excellent as an antibacterial agent.
〈従来の技術〉
式（１１）の化合物の製造中間体としては、以下の式（
ＩＩＩ ）の化合物（特開昭６１−７２８０号公報参照
）が知られている。<Prior art> As a manufacturing intermediate for the compound of formula (11), the following formula (
The compound III) (see JP-A-61-7280) is known.
しかしながら、式（ＩＩＩ）の化合物は、安定性に劣り
、又該化合物より式（Ｉｆ ）の目的化合物を製造した
場合目的物の純度及び収率の点において不満足であった
。However, the compound of formula (III) has poor stability, and when the target compound of formula (If) was produced from the compound, the purity and yield of the target product were unsatisfactory.
〈発明が解決しようとする問題点〉
本発明者等は、上記問題点を解決すべく鋭意検討した結
果本発明を完成した。<Problems to be Solved by the Invention> The present inventors have completed the present invention as a result of intensive studies to solve the above problems.
〈発明の構成〉 本発明は式（りの化合物及びその水和物に関する。<Structure of the invention> The present invention relates to compounds of formula (RI) and hydrates thereof.
式（Ｉ）の化合物は以下の方法により製造することがで
きる。The compound of formula (I) can be produced by the following method.
即ち、式（ｒＶ）の化合物又はその塩酸塩等の塩の水溶
液中に過剰のホウフッ化水素酸を反応させ、次いでイソ
プロピルアルコールを用いて晶析させることにより式（
１）の化合物を単離することができる。ホウフッ化水素
酸は通常式（ＩＶ）の化合物に対して２倍モル以上、好
ましくは５倍モル以上使用される。又、イソプロピルア
ルコールは式（ｒ’／）の化合物に対し通常２５倍部以
上使用される０反応は通常室温以下で、好ましくは水冷
下で行なわれる。That is, by reacting excess fluoroboric acid with an aqueous solution of the compound of formula (rV) or a salt such as its hydrochloride, and then crystallizing using isopropyl alcohol, the compound of formula (
The compound of 1) can be isolated. Hydrofluoroboric acid is usually used in an amount of 2 times or more, preferably 5 times or more, based on the compound of formula (IV). Further, the reaction in which isopropyl alcohol is usually used in an amount of 25 times or more relative to the compound of formula (r'/) is usually carried out at room temperature or below, preferably under water cooling.
又、式（りの化合物より式（１１）の化合物を製造する
には以下のようにすればよい。Furthermore, the compound of formula (11) can be produced from the compound of formula (11) in the following manner.
（式中、Ｒは水素原子又は保護基を意味する。）即ち、
式（Ｖ）の化合物又はその塩を塩化メチレン等の適当な
有機溶媒中五塩化リンと反応させ、得られる化合物を式
（１）の化合物と反応させ、次いで所望により酸を用い
て保護基を脱離させることにより式（ＩＩ）の目的化合
物を製造する事ができる。(In the formula, R means a hydrogen atom or a protective group.) That is,
A compound of formula (V) or a salt thereof is reacted with phosphorus pentachloride in a suitable organic solvent such as methylene chloride, the resulting compound is reacted with a compound of formula (1), and then, if desired, the protecting group is removed using an acid. The target compound of formula (II) can be produced by elimination.
〈発明の効果〉
式（１）の化合物は安定性に優れた化合物であり、式（
＋りの化合物の製造中間体としてきわめて有用な化合物
である。<Effect of the invention> The compound of formula (1) is a compound with excellent stability, and has the formula (
It is an extremely useful compound as an intermediate for the production of other compounds.
以下、本発明を更に実施例、参考例及び試験例により説
明する。The present invention will be further explained below with reference to Examples, Reference Examples, and Test Examples.
［実施例］
物Ａ）
７β−アミノ−３−［４−（オキサゾール−５−イル）
−１−ピリジニオコメチル−３−セフェム−４−カルボ
ン酸ｐ−メトキシベンジルエステル塩化物塩酸塩（化合
物Ｂ）３１７ｇを水１．６又に溶解し、４２％ホクフッ
化水素酸５２０ｇを加えた。この懸濁液にイソプロピル
アルコール８ｆｔを加えた後、析出物を濾取し、イソプ
ロピルアル−コールで洗い真空乾燥し、標題化合物２６
２ｇを得た。[Example] Product A) 7β-amino-3-[4-(oxazol-5-yl)
317 g of -1-pyridiniocomethyl-3-cephem-4-carboxylic acid p-methoxybenzyl ester chloride hydrochloride (compound B) was dissolved in 1.6 g of water, and 520 g of 42% hydrofluoric acid was added. . After adding 8 ft of isopropyl alcohol to this suspension, the precipitate was collected by filtration, washed with isopropyl alcohol, and dried under vacuum to obtain the title compound 26.
2g was obtained.
ＫＢｒ −１
１Ｒｖｃｍ ： １７８０ （β−ラクタム）ｍａ
×
ＦＴ−ＮＭＲ（０２０，δｐｐｍ） ：３．５９ 、３
．９８ （各ＩＨ、各ｄ 、Ｊ”１９．３Ｈｚ 、セ
フェム環２位のＨ）
３．６０ （３Ｈ、ｓ 、メトキシ基）５．１７〜５．
７９ （８Ｈ、ｍ 、セフェム′ｐＡ６位と７位のＨ、
！１−メトキシベンジルエステルのメチレン及びセフエ
ム３］３位のメチレン）６．７３ 、７．１８ （各
２８ 、各ｄ 、 Ｊ−８，８Ｈｚ 、 ｐ −メトキ
シベンジルエステルのフェニルのＨ）
７．９９ （２Ｈ、ｄ 、 Ｊ−７，０Ｈｚ 、ピリジ
ン環３位及び５位のＨ）
８．１５ （１）１ 、Ｓ 、オキサゾール環４位のＨ
）８．５７ （２Ｈ、ｄ 、 Ｊ＝７．０Ｈｚ 、ピリ
ジン環２位及び６位のＨ）
［１，５９（ＩＨ、Ｓ 、オキサゾール環２位のＨ）カ
ールフィッシャー法による水分測定値：３．鯖元素分析
Ｃｘ４ＨｘａＮａＯｓＳＢｔＦａ・３／２ＨｔＯに対
して理論値 Ｃ４２，３２、Ｈ３，９９、Ｎ ８．２３
分析値 Ｃ４２，３７、Ｈ３，９４、Ｎ ８．１４得ら
れた標題化合物の結晶はニッケルをフィルターとするん
＝ １．５４１８人の銅Ｘ線を用いた粉末Ｘ線回折［ｄ
＝格子面間隔］を行うと以下の特性を示す。KBr-1 1Rvcm: 1780 (β-lactam) ma
× FT-NMR (020, δppm): 3.59, 3
．． 98 (Each IH, each d, J''19.3Hz, H at 2-position of cephem ring) 3.60 (3H, s, methoxy group) 5.17-5.
79 (8H, m, H at positions 6 and 7 of Cephem' pA,
! Methylene of 1-methoxybenzyl ester and cefem 3] methylene at position 3) 6.73, 7.18 (each 28, each d, J-8,8Hz, H of phenyl of p-methoxybenzyl ester) 7.99 ( 2H, d, J-7,0Hz, H at the 3rd and 5th positions of the pyridine ring) 8.15 (1) 1, S, H at the 4th position of the oxazole ring
) 8.57 (2H, d, J = 7.0Hz, H at the 2nd and 6th positions of the pyridine ring) [1,59 (IH, S, H at the 2nd position of the oxazole ring) Moisture measurement value by Karl Fischer method: 3 ．． Mackerel elemental analysis Theoretical values for Cx4HxaNaOsSBtFa・3/2HtO C42,32, H3,99, N 8.23
Analysis values C42,37, H3,94, N 8.14 The crystals of the title compound obtained were analyzed by powder X-ray diffraction using copper X-rays using a nickel filter = 1.5418 [d
= lattice spacing] shows the following characteristics.
ｄ 強度 ｄ 強度
９．８３ ｍ ４．６７ ｖｓ９．０３ ｍ
４．２５胃
７．９７ 胃ｄ ４．２
３ ｍ７．０５ 胃
４．１５
Ｓ６．１９ 胃ｄ
４．０６ 胃５．６１
胃 ３
．９７ ｔｒｒ５．４４
胃
３．８０ 胃５．２８
胃 ３．６
９ ｓ５．０４ ｍ ３
．５４ ｍ
４．８５ ｍ ３．４６ ｗ
但し表中、Ｓは「強Ｊ、ｍは「中等度Ｊ、Ｗは「弱」、
■「非常に」、モしてｄは「拡散」をそれぞれ意味する
。d Intensity d Intensity 9.83 m 4.67 vs 9.03 m
4.25 Stomach 7.97 Stomach d 4.2
3 m7.05 Stomach 4.15
S6.19 Stomach d
4.06 Stomach 5.61
stomach 3
．． 97 trr5.44
stomach
3.80 Stomach 5.28
Stomach 3.6
9 s5.04 m3
．． 54 m 4.85 m 3.46 w However, in the table, S means "strong J", m means "moderate J", W means "weak",
■“Very”, mo and d mean “diffuse” respectively.
［参考例］
オ メチル−３−セフェム−４−カルボキシレート硫酸
塩
五塩化リン９４ｇを塩化メチレン４．５１に溶解後、−
２０℃に冷却した。攪拌しながら２−（２−トリチルア
ミノチアゾール−４−イル）−２−メトキシイミノ酢酸
１４４ｇを加え、同温でさらに４０分間攪拌した。この
ようにして得られた酸クロリド溶液を一３０℃に冷却し
た後、攪拌しながら化合物Ａ２０４ｇを加えた。ついで
、ビストリメチルシリルアセトアミド４５０ ｍｊｌ
を１１の塩化メチレンに溶解した溶液を一２０℃以下に
保ちながら滴下し、−２０℃で１時間攪拌した１反応後
イソプロピルエーテル２８ｆｔを加え析出物を濾取し、
得られた粉末にトリフロロ酢酸９００ ｍｌＬとアニ
ソール９０Ｉ１１１を加え水冷下２時間攪拌した。[Reference Example] After dissolving 94 g of methyl-3-cephem-4-carboxylate sulfate phosphorus pentachloride in 4.51 g of methylene chloride, -
Cooled to 20°C. While stirring, 144 g of 2-(2-tritylaminothiazol-4-yl)-2-methoxyiminoacetic acid was added, and the mixture was further stirred at the same temperature for 40 minutes. After cooling the acid chloride solution thus obtained to -30° C., 204 g of Compound A was added with stirring. Then, 450 mjl of bistrimethylsilylacetamide
A solution of 11 dissolved in methylene chloride was added dropwise while keeping the temperature below -20°C, and stirred for 1 hour at -20°C. After one reaction, 28ft of isopropyl ether was added and the precipitate was collected by filtration.
900 ml of trifluoroacetic acid and 90I111 of anisole were added to the obtained powder, and the mixture was stirred for 2 hours under water cooling.
反応後イソプロピルエーテル２．７ ＪＺを加え析出物
を濾取する。得られる粉末を吸着樹脂により精製し、目
的物を含む分画を濃縮後、２規定硫酸を加え析出晶を濾
取し、標題化合物８０ｇを得た。After the reaction, 2.7 JZ of isopropyl ether is added and the precipitate is collected by filtration. The resulting powder was purified using an adsorption resin, the fraction containing the target product was concentrated, 2N sulfuric acid was added, and the precipitated crystals were collected by filtration to obtain 80 g of the title compound.
ＫＢｒ −１
１ＲＶ ｃｍ ： １７９２ （β−ラクタム
）ａｘ
ＦＴ−ＮＭＲ（０２０，δｐｐｍ）：
３．５０ 、３．７２ （２Ｈ、ＡＢｑ 、 Ｊ−１
８）１ｚ 、セフェム環２位のＨ）
４．０５ （３Ｈ、ｓ 、メトキシ基）５．３２ （Ｉ
Ｈ、ｄ 、 Ｊ＝５）１ｚ 、セフェム環６位のＨ）５
．３６ 、５．６０ （２Ｈ、ＡＢｑ 、Ｊ＝１４Ｈ
ｚ 、セフェム環３位のメチレン）
５．８９ （ＩＨ、ｄ 、 Ｊ＝５Ｈｘ 、セフェム環
７位の旧７．１３ （ＬＨ、ｓ 、チアゾール環５位の
Ｈ）８．２０ （ＩＨ、ｓ 、オキサゾール環４位のＨ
）８．３３ （２Ｈ、ｄ 、 Ｊ−７Ｈｘ 、ピリジン
環３位及び５位のＨ）
８．５５ （ＩＨ、ｓ 、オキサゾール環２位のＨ）８
．９７ （２Ｈ、ｄ 、 Ｊ＝７Ｈｚ 、ピリジン環２
位及び６位のＨ）
試験例
化合物Ａ及び化合物Ｂを下記に示す条件で保存し、その
安定性（残存率）を高速液体クロマトグラフィーを用い
て検討した。結果を以下の表に示した。KBr-1 1RV cm: 1792 (β-lactam) ax FT-NMR (020, δppm): 3.50, 3.72 (2H, ABq, J-1
8) 1z, H at the 2nd position of the cephem ring) 4.05 (3H, s, methoxy group) 5.32 (I
H, d, J=5)1z, H)5 at position 6 of cephem ring
．． 36, 5.60 (2H, ABq, J=14H
z, methylene at position 3 of the cephem ring) 5.89 (IH, d, J=5Hx, former 7.13 (LH, s, H at position 5 of thiazole ring) 8.20 (IH, s, H at position 4 of oxazole ring
) 8.33 (2H, d, J-7Hx, H at the 3- and 5-positions of the pyridine ring) 8.55 (IH, s, H at the 2-position of the oxazole ring) 8
．． 97 (2H, d, J=7Hz, pyridine ring 2
and H at the 6th position) Test Example Compound A and Compound B were stored under the conditions shown below, and their stability (residual rate) was examined using high performance liquid chromatography. The results are shown in the table below.
高速液体クロマトグラフィーの条件
カラム： ＹＭ［； ｐａｃｋｅｄ ｃｏｌｕｍｎ Ａ
−３１２？８’１Ｍ液：水、アセトニトリル、酢酸及び
トリエチルアミン（１０００：５００：１０：２．５、
（Ｖ））の混液
上表から明らかなように本発明化合物は対照化合物に比
べ優れた安定性を示し、且つ吸湿性においても優れてい
た。Conditions for high performance liquid chromatography Column: YM [; packed column A
-312?8'1M solution: water, acetonitrile, acetic acid and triethylamine (1000:500:10:2.5,
As is clear from the above table of the mixture of (V)), the compound of the present invention exhibited superior stability compared to the control compound, and was also superior in hygroscopicity.
Claims (1)
−５−イル）−１−ピリジニオ］メチル−３−セフェム
−４−カルボン酸ｐ−メトキシベンジルエステルホウフ
ッ化物・ホウフッ化水素酸塩及びその水和物[Claims] 7β-Amino-3-[4-(oxazol-5-yl)-1-pyridinio]methyl-3-cephem-4-carvone represented by the formula ▲ Numerical formulas, chemical formulas, tables, etc. ▼ Acid p-methoxybenzyl ester borofluoride/hydroboric acid salt and its hydrate
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP63082781A JP2568245B2 (en) | 1988-04-04 | 1988-04-04 | 3-Cephem derivative borofluoride / borofluoride |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP63082781A JP2568245B2 (en) | 1988-04-04 | 1988-04-04 | 3-Cephem derivative borofluoride / borofluoride |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH01254687A true JPH01254687A (en) | 1989-10-11 |
| JP2568245B2 JP2568245B2 (en) | 1996-12-25 |
Family
ID=13783958
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP63082781A Expired - Fee Related JP2568245B2 (en) | 1988-04-04 | 1988-04-04 | 3-Cephem derivative borofluoride / borofluoride |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2568245B2 (en) |
-
1988
- 1988-04-04 JP JP63082781A patent/JP2568245B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| JP2568245B2 (en) | 1996-12-25 |
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