DE2927539A1 - Bis:di:ethanol-amino-di:piperidino-pyrimido-pyrimidine prepn. - from methyl acetoacetate and urea via amino-orotic acid - Google Patents
Bis:di:ethanol-amino-di:piperidino-pyrimido-pyrimidine prepn. - from methyl acetoacetate and urea via amino-orotic acidInfo
- Publication number
- DE2927539A1 DE2927539A1 DE19792927539 DE2927539A DE2927539A1 DE 2927539 A1 DE2927539 A1 DE 2927539A1 DE 19792927539 DE19792927539 DE 19792927539 DE 2927539 A DE2927539 A DE 2927539A DE 2927539 A1 DE2927539 A1 DE 2927539A1
- Authority
- DE
- Germany
- Prior art keywords
- pyrimidine
- pyrimido
- amino
- bis
- orotic acid
- 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.)
- Withdrawn
Links
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 title claims abstract description 6
- 239000004202 carbamide Substances 0.000 title claims abstract description 6
- WRQNANDWMGAFTP-UHFFFAOYSA-N Methylacetoacetic acid Chemical compound COC(=O)CC(C)=O WRQNANDWMGAFTP-UHFFFAOYSA-N 0.000 title abstract description 3
- HWCXJKLFOSBVLH-UHFFFAOYSA-N 5-amino-2,4-dioxo-1h-pyrimidine-6-carboxylic acid Chemical compound NC1=C(C(O)=O)NC(=O)NC1=O HWCXJKLFOSBVLH-UHFFFAOYSA-N 0.000 title abstract 2
- IZEKFCXSFNUWAM-UHFFFAOYSA-N dipyridamole Chemical compound C=12N=C(N(CCO)CCO)N=C(N3CCCCC3)C2=NC(N(CCO)CCO)=NC=1N1CCCCC1 IZEKFCXSFNUWAM-UHFFFAOYSA-N 0.000 claims abstract description 5
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 239000002253 acid Substances 0.000 claims description 3
- 238000009833 condensation Methods 0.000 claims 3
- 230000005494 condensation Effects 0.000 claims 3
- 230000001419 dependent effect Effects 0.000 claims 2
- 238000006467 substitution reaction Methods 0.000 claims 2
- 238000005660 chlorination reaction Methods 0.000 claims 1
- 238000000034 method Methods 0.000 claims 1
- 238000006396 nitration reaction Methods 0.000 claims 1
- 230000003647 oxidation Effects 0.000 claims 1
- 238000007254 oxidation reaction Methods 0.000 claims 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 1
- 238000000746 purification Methods 0.000 claims 1
- 230000009467 reduction Effects 0.000 claims 1
- 238000006722 reduction reaction Methods 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 abstract description 9
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 abstract description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 abstract description 4
- 229910017604 nitric acid Inorganic materials 0.000 abstract description 4
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 abstract description 2
- XBCXJKGHPABGSD-UHFFFAOYSA-N methyluracil Natural products CN1C=CC(=O)NC1=O XBCXJKGHPABGSD-UHFFFAOYSA-N 0.000 abstract description 2
- HYHCSLBZRBJJCH-UHFFFAOYSA-M sodium hydrosulfide Chemical compound [Na+].[SH-] HYHCSLBZRBJJCH-UHFFFAOYSA-M 0.000 abstract description 2
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 abstract description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 abstract 2
- ZEKJTVBUDUYZOU-UHFFFAOYSA-N 1,5-dihydropyrimido[5,4-d]pyrimidine-2,4,6,8-tetrone Chemical compound O=C1NC(=O)NC2=C1NC(=O)NC2=O ZEKJTVBUDUYZOU-UHFFFAOYSA-N 0.000 abstract 1
- QNKFHUMDHRWWES-UHFFFAOYSA-N 2,4,6,8-tetrachloropyrimido[5,4-d]pyrimidine Chemical compound N1=C(Cl)N=C(Cl)C2=NC(Cl)=NC(Cl)=C21 QNKFHUMDHRWWES-UHFFFAOYSA-N 0.000 abstract 1
- PCVJQTVUJJJSRQ-UHFFFAOYSA-N 2,6-dichloro-4,8-di(piperidin-1-yl)pyrimido[5,4-d]pyrimidine Chemical compound C=12N=C(Cl)N=C(N3CCCCC3)C2=NC(Cl)=NC=1N1CCCCC1 PCVJQTVUJJJSRQ-UHFFFAOYSA-N 0.000 abstract 1
- OPGJGRWULGFTOS-UHFFFAOYSA-N 5-nitro-2,4-dioxo-1h-pyrimidine-6-carboxylic acid Chemical compound OC(=O)C=1NC(=O)NC(=O)C=1[N+]([O-])=O OPGJGRWULGFTOS-UHFFFAOYSA-N 0.000 abstract 1
- 229910019213 POCl3 Inorganic materials 0.000 abstract 1
- KHPVNEHMLTYJMC-UHFFFAOYSA-N [O-][N+](=O)Cc1c[nH]c(=O)[nH]c1=O Chemical compound [O-][N+](=O)Cc1c[nH]c(=O)[nH]c1=O KHPVNEHMLTYJMC-UHFFFAOYSA-N 0.000 abstract 1
- 230000000802 nitrating effect Effects 0.000 abstract 1
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 abstract 1
- 239000000047 product Substances 0.000 description 8
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 3
- YKRQHJBBCGNVSD-UHFFFAOYSA-N 2,4-di(piperidin-1-yl)pyrimido[5,4-d]pyrimidine Chemical compound C1CCCCN1C1=NC(N2CCCCC2)=C(N=CN=C2)C2=N1 YKRQHJBBCGNVSD-UHFFFAOYSA-N 0.000 description 1
- AMLGLAJHMGOEHW-UHFFFAOYSA-N Cc1c([nH]c(=O)[nH]c1=O)[N+]([O-])=O Chemical compound Cc1c([nH]c(=O)[nH]c1=O)[N+]([O-])=O AMLGLAJHMGOEHW-UHFFFAOYSA-N 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- LIGHQFMXKLNVMQ-UHFFFAOYSA-N [Cl].[Cl].[Cl].[P] Chemical compound [Cl].[Cl].[Cl].[P] LIGHQFMXKLNVMQ-UHFFFAOYSA-N 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 125000003963 dichloro group Chemical group Cl* 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 150000003230 pyrimidines Chemical group 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
Beschreibung der Erfindung Description of the invention
Titel: Neue Technologie für die Produktion von 2,6 - Bis (diäthanolamino) - 4,8 - dipiperidino - pyrimido - (5,4-d) pyrimidin Anwendungsgebiet: Die Erfindung betrifft eine neue Technologie für die industriemäßige Produktion von 2,6 - Bis (diäthanolamino) - 4,8 -dipiperidino - pyrimidin (5,4-d) pyrimidin Zweck: Rationellere Produktion des im Titel genannten Stoffes Stand der Technik: Die herkömmliche technologische Produktion hat einen wesentlich- geringeren Wirkungsgrad als die Erfindung bei gleichem Reinheitsgrad; somit liegen die bisherigen Produktionskosten wesentlich höher.Title: New technology for the production of 2,6 - bis (diethanolamino) - 4,8 - dipiperidino - pyrimido - (5,4-d) pyrimidine Field of application: The invention concerns a new technology for industrial production of 2,6 - bis (diethanolamino) - 4,8 -dipiperidino - pyrimidine (5,4-d) pyrimidine Purpose: More rational Production of the substance mentioned in the title State of the art: The conventional technological Production has a much lower efficiency than the invention with the same Degree of purity; thus the previous production costs are significantly higher.
Lösung: 20 kg Acetessigsäuremethylester kondensieren mit 2 kg Harnstoff in Methylalkohol Temperatur: 250 bis 1000C Dauer: .1 bis 4 Stunden Das Produkt Methyluracil nitrieren mit 5 kg Salpetersäure Temperatur: - 300C bis 120°C Dauer 0,1 bis 2 Stunden Das Produkt Nitro Methyluracil oxydieren mit 20 kg Salpetersäure Temperatur: 10°C bis 1800C Dauer 0,1 bis 6 Stunden Dan Axente Margineanu Das Produkt Nitrocrotiosäure reduzieren mit 10 kg natriumhydrosulfid Temperatur: 10°C bis 100°C Dauer: 0,1 bis 6 Stunden Das Produkt Aminocrotiosäure kondensieren mit 1 kg Harnstoff Temperatur: 10°C bis 300°C Paner: 0,1 bis 5 Stunden Das Produkt 2,4,6,8 hydroxi pirimido (5,4-d) pyrimidin chlorieren mit 40 kg Phosphoroxychlor (PO Cl32) und 2 kg Phosphortrichlor (PCl3) Temperatur: -10°C bis 180°C Dauer: 0,1 bis 10 Stunden Das Produkt 2,4,6,8 chlor pirimido (5,4-d) pyrimidin substituieren mit 1 kg Piperidin Temperatur: 0°C bis 100°c Dauer: 0,1 bis 12 Stunden Das Produkt 2,6 (dichlor) 4,8 dipiperidino (5,4-d) pyrimidin substituierten mit 1 kg Diäthanolamin Temperatur: 5°C bis 350°C Dauer: 0,1 bis 24 Stunden Das Produkt 2,6 - Bis (diäthanolamino) 4,8 - dipiperidino - pyrimido - (5,4-d) pyrimidin reinigen mit 20 kg Methanol Endprodukt: 1 kg 2,6 - Bis (diäthanolamino)-4,8 dipiperidino - pyrimido (5,4-d) pyrimidin bei einem Reinheitsgrad von 99,5% Solution: 20 kg of methyl acetoacetate condense with 2 kg of urea in methyl alcohol Temperature: 250 to 1000C Duration: 1 to 4 hours Nitrate the product Methyluracil with 5 kg of nitric acid Temperature: - 300C to 120 ° C Duration 0.1 to 2 hours The product Nitro Methyluracil oxidize with 20 kg of nitric acid Temperature: 10 ° C to 1800C Duration 0.1 to 6 hours Dan Axente Margineanu Reduce the product nitrocrotioic acid with 10 kg sodium hydrosulfide Temperature: 10 ° C to 100 ° C Duration: 0.1 to 6 hours The product aminocrotioic acid condense with 1 kg urea Temperature: 10 ° C to 300 ° C Paner: 0.1 up to 5 hours chlorinate the product 2,4,6,8 hydroxi pirimido (5,4-d) pyrimidine with 40 kg phosphorus oxychlor (PO Cl32) and 2 kg phosphorus trichlor (PCl3) Temperature: -10 ° C to 180 ° C Duration: 0.1 to 10 hours Substitute the product 2,4,6,8 chloropirimido (5,4-d) pyrimidine with 1 kg of piperidine Temperature: 0 ° C to 100 ° C Duration: 0.1 to 12 hours The product 2 , 6 (dichloro) 4,8 dipiperidino (5,4-d) pyrimidine substituted with 1 kg diethanolamine Temperature: 5 ° C to 350 ° C Duration: 0.1 to 24 hours The product 2,6 - bis (diethanolamino) 4 , 8 - dipiperidino - pyrimido - (5,4-d) pyrimidine Purify with 20 kg of methanol End product: 1 kg of 2,6 - bis (diethanolamino) -4.8 dipiperidino - pyrimido (5,4-d) pyrimidine at one degree of purity of 99.5%
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19792927539 DE2927539A1 (en) | 1979-07-07 | 1979-07-07 | Bis:di:ethanol-amino-di:piperidino-pyrimido-pyrimidine prepn. - from methyl acetoacetate and urea via amino-orotic acid |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19792927539 DE2927539A1 (en) | 1979-07-07 | 1979-07-07 | Bis:di:ethanol-amino-di:piperidino-pyrimido-pyrimidine prepn. - from methyl acetoacetate and urea via amino-orotic acid |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE2927539A1 true DE2927539A1 (en) | 1981-01-08 |
Family
ID=6075178
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19792927539 Withdrawn DE2927539A1 (en) | 1979-07-07 | 1979-07-07 | Bis:di:ethanol-amino-di:piperidino-pyrimido-pyrimidine prepn. - from methyl acetoacetate and urea via amino-orotic acid |
Country Status (1)
| Country | Link |
|---|---|
| DE (1) | DE2927539A1 (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007080463A1 (en) * | 2006-01-12 | 2007-07-19 | Orchid Chemicals & Pharmaceuticals Limited | An improved process for the preparation of dipyridamole |
| WO2011151640A1 (en) * | 2010-05-31 | 2011-12-08 | Generics [Uk] Limited | Processes for the preparation of dipyridamole |
| CN106946887A (en) * | 2017-03-24 | 2017-07-14 | 大连万福制药有限公司 | It is a kind of to introduce the new technology that catalyst optimization synthesizes Dipyridamole |
-
1979
- 1979-07-07 DE DE19792927539 patent/DE2927539A1/en not_active Withdrawn
Cited By (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007080463A1 (en) * | 2006-01-12 | 2007-07-19 | Orchid Chemicals & Pharmaceuticals Limited | An improved process for the preparation of dipyridamole |
| WO2011151640A1 (en) * | 2010-05-31 | 2011-12-08 | Generics [Uk] Limited | Processes for the preparation of dipyridamole |
| CN103108874A (en) * | 2010-05-31 | 2013-05-15 | 基因里克斯(英国)有限公司 | Processes for the preparation of dipyridamole |
| JP2013527221A (en) * | 2010-05-31 | 2013-06-27 | ジェネリクス・［ユーケー］・リミテッド | Process for the preparation of dipyridamole |
| US8946414B2 (en) | 2010-05-31 | 2015-02-03 | Generics [Uk] Limited | Processes for the preparation of dipyridamole |
| AU2011260044B2 (en) * | 2010-05-31 | 2016-03-17 | Tianish Laboratories Private Limited | Processes for the preparation of dipyridamole |
| US9381197B2 (en) | 2010-05-31 | 2016-07-05 | Generics [Uk] Limited | Processes for the preparation of dipyridamole |
| JP2016155810A (en) * | 2010-05-31 | 2016-09-01 | ジェネリクス・［ユーケー］・リミテッド | Process for preparation of dipyridamole |
| CN103108874B (en) * | 2010-05-31 | 2016-11-16 | 基因里克斯(英国)有限公司 | For the method preparing dipyridamole |
| CN106946887A (en) * | 2017-03-24 | 2017-07-14 | 大连万福制药有限公司 | It is a kind of to introduce the new technology that catalyst optimization synthesizes Dipyridamole |
| CN106946887B (en) * | 2017-03-24 | 2019-05-28 | 大连万福制药有限公司 | A kind of preparation method introducing catalyst optimization synthesis Dipyridamole |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8139 | Disposal/non-payment of the annual fee |