JPS6094950A - ６−デメチル−６−デオキシ−６−メチレン−５−オキシテトラサイクリンおよびその１１ａ−クロロ−誘導体の製造方法 - Google Patents
６−デメチル−６−デオキシ−６−メチレン−５−オキシテトラサイクリンおよびその１１ａ−クロロ−誘導体の製造方法Info
- Publication number
- JPS6094950A JPS6094950A JP59180882A JP18088284A JPS6094950A JP S6094950 A JPS6094950 A JP S6094950A JP 59180882 A JP59180882 A JP 59180882A JP 18088284 A JP18088284 A JP 18088284A JP S6094950 A JPS6094950 A JP S6094950A
- Authority
- JP
- Japan
- Prior art keywords
- oxytetracycline
- chloro
- acid
- methylene
- mixture
- 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
- 238000004519 manufacturing process Methods 0.000 title claims description 4
- 238000000034 method Methods 0.000 claims description 24
- 239000000203 mixture Substances 0.000 claims description 24
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 22
- 238000006297 dehydration reaction Methods 0.000 claims description 13
- 239000002253 acid Substances 0.000 claims description 12
- KEQGZUUPPQEDPF-UHFFFAOYSA-N 1,3-dichloro-5,5-dimethylimidazolidine-2,4-dione Chemical compound CC1(C)N(Cl)C(=O)N(Cl)C1=O KEQGZUUPPQEDPF-UHFFFAOYSA-N 0.000 claims description 11
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 11
- XTHPWXDJESJLNJ-UHFFFAOYSA-N chlorosulfonic acid Substances OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 claims description 11
- 235000019253 formic acid Nutrition 0.000 claims description 11
- 230000018044 dehydration Effects 0.000 claims description 10
- 238000006243 chemical reaction Methods 0.000 claims description 9
- 239000011541 reaction mixture Substances 0.000 claims description 8
- 150000003839 salts Chemical class 0.000 claims description 8
- 239000002904 solvent Substances 0.000 claims description 6
- 238000002955 isolation Methods 0.000 claims description 4
- 239000003638 chemical reducing agent Substances 0.000 claims description 3
- 239000000543 intermediate Substances 0.000 claims description 3
- 239000004100 Oxytetracycline Substances 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 239000012442 inert solvent Substances 0.000 claims description 2
- 229960000625 oxytetracycline Drugs 0.000 claims description 2
- 150000008280 chlorinated hydrocarbons Chemical class 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 36
- 239000000047 product Substances 0.000 description 16
- KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 11
- 229910000040 hydrogen fluoride Inorganic materials 0.000 description 11
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 8
- 238000001816 cooling Methods 0.000 description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- 238000009835 boiling Methods 0.000 description 6
- 239000013078 crystal Substances 0.000 description 6
- LELOWRISYMNNSU-UHFFFAOYSA-N hydrogen cyanide Chemical compound N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
- 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 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 238000000354 decomposition reaction Methods 0.000 description 3
- 230000001546 nitrifying effect Effects 0.000 description 3
- 238000001556 precipitation Methods 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 description 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
- -1 alkyl sulfuric acid Chemical compound 0.000 description 2
- 238000005695 dehalogenation reaction Methods 0.000 description 2
- 239000012024 dehydrating agents Substances 0.000 description 2
- 150000004683 dihydrates Chemical class 0.000 description 2
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 2
- 229960004368 oxytetracycline hydrochloride Drugs 0.000 description 2
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
- 150000004684 trihydrates Chemical class 0.000 description 2
- 239000001715 Ammonium malate Substances 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 239000004146 Propane-1,2-diol Substances 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- AOGYCOYQMAVAFD-UHFFFAOYSA-N chlorocarbonic acid Chemical compound OC(Cl)=O AOGYCOYQMAVAFD-UHFFFAOYSA-N 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000000356 contaminant Substances 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 210000003298 dental enamel Anatomy 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000002360 explosive Substances 0.000 description 1
- 210000001508 eye Anatomy 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 231100001261 hazardous Toxicity 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 229930187294 kinoin Natural products 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- MHIGBKBJSQVXNH-IWVLMIASSA-N methacycline Chemical compound C=C([C@H]1[C@@H]2O)C3=CC=CC(O)=C3C(=O)C1=C(O)[C@@]1(O)[C@@H]2[C@H](N(C)C)C(O)=C(C(N)=O)C1=O MHIGBKBJSQVXNH-IWVLMIASSA-N 0.000 description 1
- 229940042016 methacycline Drugs 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 150000002828 nitro derivatives Chemical class 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- MOODSJOROWROTO-UHFFFAOYSA-N salicylsulfuric acid Chemical compound OC(=O)C1=CC=CC=C1OS(O)(=O)=O MOODSJOROWROTO-UHFFFAOYSA-N 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 229940071103 sulfosalicylate Drugs 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C233/12—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by halogen atoms or by nitro or nitroso groups
- C07C233/14—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by halogen atoms or by nitro or nitroso groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a ring other than a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
- C07C237/24—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a ring other than a six-membered aromatic ring of the carbon skeleton
- C07C237/26—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a ring other than a six-membered aromatic ring of the carbon skeleton of a ring being part of a condensed ring system formed by at least four rings, e.g. tetracycline
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C309/00—Sulfonic acids; Halides, esters, or anhydrides thereof
- C07C309/63—Esters of sulfonic acids
- C07C309/72—Esters of sulfonic acids having sulfur atoms of esterified sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C309/73—Esters of sulfonic acids having sulfur atoms of esterified sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton to carbon atoms of non-condensed six-membered aromatic rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| HU833061A HU188367B (en) | 1983-09-02 | 1983-09-02 | Process for preparing 6-demethy-6-deoxy-6-methylene-5-exytetracycline and 11a-chloro-derivative thereof |
| HU2251/3061/83 | 1983-09-02 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS6094950A true JPS6094950A (ja) | 1985-05-28 |
| JPH0344066B2 JPH0344066B2 (en, 2012) | 1991-07-04 |
Family
ID=10962342
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP59180882A Granted JPS6094950A (ja) | 1983-09-02 | 1984-08-31 | ６−デメチル−６−デオキシ−６−メチレン−５−オキシテトラサイクリンおよびその１１ａ−クロロ−誘導体の製造方法 |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US4659515A (en, 2012) |
| JP (1) | JPS6094950A (en, 2012) |
| KR (1) | KR910004668B1 (en, 2012) |
| BG (1) | BG44707A3 (en, 2012) |
| DD (1) | DD219186A5 (en, 2012) |
| DE (1) | DE3431009A1 (en, 2012) |
| FR (1) | FR2551435B1 (en, 2012) |
| GB (1) | GB2145722B (en, 2012) |
| HU (1) | HU188367B (en, 2012) |
| IT (1) | IT1207343B (en, 2012) |
| PL (1) | PL143307B1 (en, 2012) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5686634A (en) * | 1994-07-01 | 1997-11-11 | Pfizer, Inc. | Process for producing 5-hydroxy-6-demethyl-6-desoxy-6-methylene-11A-chlorotetracycline |
| CN104163773B (zh) * | 2013-08-30 | 2016-04-27 | 郑州后羿制药有限公司 | 一种四环素的精制方法 |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB887671A (en) * | 1958-03-05 | 1962-01-24 | American Cyanamid Co | Preparation of members of the tetracycline series |
| FR1430859A (en, 2012) * | 1960-05-23 | 1966-05-25 | ||
| US2984686A (en) * | 1960-12-19 | 1961-05-16 | Pfizer & Co C | 6-deoxy-6-demethyl-6-methylene-5-oxytetracyclines |
| US3842123A (en) * | 1969-08-08 | 1974-10-15 | L Bernardi | Methylenetetracycline formate ester |
| BE755678R (fr) * | 1969-09-04 | 1971-03-03 | Farmaceutici Italia | Esters de la methylenetetracycline et procede de leur fabrication |
| CA942743A (en) * | 1970-07-03 | 1974-02-26 | Ivan Villax | Process for producing 6-methylenetetracyclines and 6-deoxytetracyclines |
| FR2136137A5 (en) * | 1971-04-05 | 1972-12-22 | Pliva Pharm & Chem Works | Tetracycline derivs prepn - by bromination followed by dehydration |
| GB1333900A (en) * | 1971-07-08 | 1973-10-17 | Farmaceutici Italia | 6-deimethyl-6-deoxytetracycline |
| ATA571275A (de) * | 1974-08-09 | 1976-06-15 | Pliva Pharm & Chem Works | Verfahren zur herstellung von 11a-chlor-6-methylen-5-hydroxy-tetracyclin-p-toluolsulfonat |
-
1983
- 1983-09-02 HU HU833061A patent/HU188367B/hu not_active IP Right Cessation
-
1984
- 1984-08-23 DE DE19843431009 patent/DE3431009A1/de active Granted
- 1984-08-30 IT IT8467863A patent/IT1207343B/it active
- 1984-08-31 KR KR1019840005370A patent/KR910004668B1/ko not_active Expired
- 1984-08-31 BG BG066763A patent/BG44707A3/xx unknown
- 1984-08-31 JP JP59180882A patent/JPS6094950A/ja active Granted
- 1984-08-31 PL PL1984249429A patent/PL143307B1/pl unknown
- 1984-08-31 FR FR8413504A patent/FR2551435B1/fr not_active Expired
- 1984-08-31 DD DD84266854A patent/DD219186A5/de not_active IP Right Cessation
- 1984-08-31 US US06/646,574 patent/US4659515A/en not_active Expired - Fee Related
- 1984-08-31 GB GB08422041A patent/GB2145722B/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| HU188367B (en) | 1986-04-28 |
| HUT35632A (en) | 1985-07-29 |
| GB2145722B (en) | 1987-07-08 |
| FR2551435B1 (fr) | 1989-01-20 |
| IT8467863A0 (it) | 1984-08-30 |
| JPH0344066B2 (en, 2012) | 1991-07-04 |
| FR2551435A1 (fr) | 1985-03-08 |
| BG44707A3 (bg) | 1989-01-16 |
| GB8422041D0 (en) | 1984-10-03 |
| DD219186A5 (de) | 1985-02-27 |
| IT1207343B (it) | 1989-05-17 |
| KR910004668B1 (ko) | 1991-07-09 |
| US4659515A (en) | 1987-04-21 |
| DE3431009C2 (en, 2012) | 1990-07-26 |
| DE3431009A1 (de) | 1985-03-21 |
| PL143307B1 (en) | 1988-02-29 |
| GB2145722A (en) | 1985-04-03 |
| KR850002457A (ko) | 1985-05-13 |
| PL249429A1 (en) | 1985-05-07 |
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