PL59331B1 - - Google Patents
Download PDFInfo
- Publication number
- PL59331B1 PL59331B1 PL122085A PL12208567A PL59331B1 PL 59331 B1 PL59331 B1 PL 59331B1 PL 122085 A PL122085 A PL 122085A PL 12208567 A PL12208567 A PL 12208567A PL 59331 B1 PL59331 B1 PL 59331B1
- Authority
- PL
- Poland
- Prior art keywords
- substituted
- amino
- carried out
- guanidine
- group
- Prior art date
Links
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 15
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 15
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 10
- 238000000034 method Methods 0.000 claims description 9
- ZRALSGWEFCBTJO-UHFFFAOYSA-N guanidine group Chemical group NC(=N)N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 claims description 8
- OAKJQQAXSVQMHS-UHFFFAOYSA-N hydrazine group Chemical group NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 8
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 6
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Chemical group CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 claims description 4
- 238000006243 chemical reaction Methods 0.000 claims description 4
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Chemical group CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 claims description 4
- 229910021529 ammonia Inorganic materials 0.000 claims description 3
- 229910052757 nitrogen Inorganic materials 0.000 claims description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 2
- 150000005725 2,4-diamino-6-chloropyrimidines Chemical class 0.000 claims description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 2
- 150000001412 amines Chemical class 0.000 claims description 2
- 150000002357 guanidines Chemical class 0.000 claims description 2
- 150000002391 heterocyclic compounds Chemical class 0.000 claims description 2
- 125000000623 heterocyclic group Chemical group 0.000 claims description 2
- 150000002429 hydrazines Chemical class 0.000 claims description 2
- 229910000041 hydrogen chloride Inorganic materials 0.000 claims description 2
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 claims description 2
- 239000012442 inert solvent Substances 0.000 claims description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 claims description 2
- 150000003512 tertiary amines Chemical class 0.000 claims description 2
- 239000008096 xylene Substances 0.000 claims description 2
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims 1
- -1 aliphatic primary Chemical class 0.000 claims 1
- 239000011230 binding agent Substances 0.000 claims 1
- 125000004663 dialkyl amino group Chemical group 0.000 claims 1
- 125000004433 nitrogen atom Chemical group N* 0.000 claims 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 1
- 239000000376 reactant Substances 0.000 claims 1
- 150000003335 secondary amines Chemical class 0.000 claims 1
- UPVBKNZVOJNQKE-UHFFFAOYSA-N 2,6-dichloropyrimidin-4-amine Chemical compound NC1=CC(Cl)=NC(Cl)=N1 UPVBKNZVOJNQKE-UHFFFAOYSA-N 0.000 description 6
- 239000000203 mixture Substances 0.000 description 5
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- DPVIABCMTHHTGB-UHFFFAOYSA-N 2,4,6-trichloropyrimidine Chemical compound ClC1=CC(Cl)=NC(Cl)=N1 DPVIABCMTHHTGB-UHFFFAOYSA-N 0.000 description 1
- QJIUMVUZDYPQRT-UHFFFAOYSA-N 6-chloro-2,4-pyrimidinediamine Chemical compound NC1=CC(Cl)=NC(N)=N1 QJIUMVUZDYPQRT-UHFFFAOYSA-N 0.000 description 1
- CAPWCRRKZOKFTE-UHFFFAOYSA-N 6-chloro-2-morpholin-4-ylpyrimidin-4-amine Chemical compound NC1=CC(Cl)=NC(N2CCOCC2)=N1 CAPWCRRKZOKFTE-UHFFFAOYSA-N 0.000 description 1
- NMWKOBZHKWXQFS-UHFFFAOYSA-N 6-chloro-2-n,2-n-dimethylpyrimidine-2,4-diamine Chemical compound CN(C)C1=NC(N)=CC(Cl)=N1 NMWKOBZHKWXQFS-UHFFFAOYSA-N 0.000 description 1
- BSFBUEBSAVYQQR-UHFFFAOYSA-N 6-chloro-2-n-methylpyrimidine-2,4-diamine Chemical compound CNC1=NC(N)=CC(Cl)=N1 BSFBUEBSAVYQQR-UHFFFAOYSA-N 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
Description
Opublikowano: 15.IV.1970 59331 KI. 12 p, 7/01 MKP C07d 5*\k UKD f\ "lirowego Wspóltwórcy wynalazku: prof. dr Pawel Nantka-Namirski, mgr inz. Jan Wojciechowski Wlasciciel patentu: Instytut Farmaceutyczny, Warszawa (Polska) Sposób wytwarzania pochodnych 2,4-dwuamino-6-chloropirymidyny Przedmiotem wynalazku jest sposób wytwarzania pochodnych 2,4-dwuamino-6-chloropirymidyny o ogólnym wzorze przedstawionym na rysunku, w którym R oznacza grupe aminowa, jedno- i dwu- alkiloaminowa, przy czym oba rodniki alkilowe lacznie z atomem azotu tworza takze pierscien he¬ terocykliczny, taki jak piperydynowy, morfolinowy, ponadto R oznacza grupe guanidynowa wolna lub podstawiona i grupe hydrazynowa wolna lub pod¬ stawiona. Zwiazki te stanowia produkty posrednie w syntezie zwiazków o dzialaniu terapeutycznym.Wedlug opisu patentowego nr 48869 zwiazki te otrzymuje sie z 2, 4, 6-trójchloropirymidyny lub z 2-alkiloamino-4,6-dwuchlorqpirymidyny dziala¬ niem amoniaku.Stwierdzono, ze zwiazki, których sposób wytwa¬ rzania jest przedmiotem wynalazku, mozna otrzy¬ mac z 2,6-dwuchloro-4-aminopirymidyny, która jest latwo dostepnym produktem wyjsciowym stosowa¬ nym w syntezie sulfonamidów.Wedlug wynalazku 2,6-dwuchloro-4-aminopirymi- dyne poddaje sie dzialaniu amoniaku, alifatycznej aminy pierwszo- lub drugorzedowej, zwiazku hete¬ rocyklicznego zawierajacego w pierscieniu drugo- rzedowy azot, guanidyny, podstawionej guanidyny, hydrazyny lub podstawionej hydrazyny. Reakcje prowadzi sie w srodowisku obojetnego rozpuszczal¬ nika takiego jak metanol, etanol, dwuoksan, ben¬ zen, ksylen, dwumetyloformamid w temperaturze 20—80°. Stosuje sie przy tym nadmiar aminy, wzgle- 10 15 20 30 dnie dodaje sie trzeciorzedowa amine w celu zwia¬ zania powstajacego chlorowodoru.Przyklad I. Do roztworu 16,4 g 2,6-dwuchlo- ro-4-aminopirymidyny w 50 ml metanolu wkroplo- no w temperaturze okolo 60° roztwór 13 g pipery- dyny w 25 ml metanolu. Mieszanine utrzymywano w temperaturze wrzenia w ciagu 2 godzin, po czym wylano do 450 ml wody. Wytracony osad odsaczo¬ no i przekrystalizowano z mieszaniny metanol — woda 2:1. Otrzymano 2-piperydyno-4-amino-6-chlo- ropirymidyne o temperaturze topnienia 155—157°.Przyklad II. Do roztworu 16,4 g 2,6-dwu- chloro-4-amino-pirymidyny w 60 ml benzenu wkro- plono w temperaturze 50—60° roztwór 4,5 g dwume- tyloaminy oraz 6 g trój mety loaminy w 70 ml ben¬ zenu. Mieszanine ogrzewano w ciagu 3 godzin w temperaturze 60—70°, nastepnie oddestylowano roz¬ puszczalnik i nadmiar trój mety loaminy, a pozosta¬ losc przekrystalizowano z mieszaniny metanol — woda 1:1. Otrzymano 2-dwumetyloamino-4-amino- 6-chloropirymidyne o temperaturze topnienia 154— 156°.Przyklad III. Do roztworu 16,4 g 2,6-dwu- chloro-4-aminopirymidyny w 30 ml etanolu dodano 25 g morfoliny, po czym mieszanine ogrzewano w ciagu 1 godziny w temperaturze 70°. Nastepnie do¬ dano 150 ml wody i wytracony osad przekrystali¬ zowano z metanolu. Otrzymano 2-morfolino-4-ami- no-6-chloropirymidyne o temperaturze topnienia 156-158°. 5933159331 Przyklad IV. Do roztworu 16,4 g 2,6-dwu- chloro-4-aminopirymidyny w 50 ml etanolu wkro- plono roztwór 10 g metyloaminy w 40 ml benzenu.Mieszanine utrzymywano w ciagu godziny w tem¬ peraturze 20° i nastepnie w ciagu 2 godzin w tem¬ peraturze 40—50°. Po oddestylowaniu rozpuszczalni¬ ków pozostalosc przemyto woda i przekrystalizowa- no z etanolu. Otrzymano 2-metyloamino-4-amino-6- chloropirymidyne o temperaturze topnienia 208— 210°. PLPublished: 15.IV.1970 59331 KI. 12 p, 7/01 MKP C07d 5 * \ k UKD f \ "lirish Inventors of the invention: prof. Dr. Pawel Nantka-Namirski, mgr inz. Jan Wojciechowski Patent owner: Pharmaceutical Institute, Warsaw (Poland) Method for the production of 2,4- derivatives Diamino-6-chloropyrimidine The subject of the invention is a process for the preparation of 2,4-diamino-6-chloropyrimidine derivatives with the general formula shown in the figure, in which R represents an amino group, a mono-alkyl and a di-alkylamino group, both of which are It also forms a heterocyclic ring, such as piperidine, morpholino, and, moreover, R represents a free or substituted guanidine group and a free or substituted hydrazine group. These compounds are intermediates in the synthesis of compounds with a therapeutic effect. from 2, 4, 6-trichloropyrimidine or from 2-alkylamino-4,6-dichloropyrimidine by the action of ammonia. It has been found that the compounds whose production is the subject of the invention It can be obtained from 2,6-dichloro-4-aminopyrimidine, which is an readily available starting product used in the synthesis of sulfonamides. According to the invention, 2,6-dichloro-4-aminopyrimidine is treated with ammonia, an aliphatic amine. a primary or secondary, heterocyclic compound containing a secondary nitrogen in the ring, guanidine, substituted guanidine, hydrazine or substituted hydrazine. The reactions are carried out in an inert solvent such as methanol, ethanol, dioxane, benzene, xylene, dimethylformamide at a temperature of 20 ° to 80 °. An excess of the amine is used, or a tertiary amine is added for 30 days in order to bind the hydrogen chloride formed. Example 1 To a solution of 16.4 g of 2,6-dichloro-4-aminopyrimidine in 50 ml of methanol A solution of 13 g of piperidine in 25 ml of methanol was added dropwise at a temperature of about 60 °. The mixture was refluxed for 2 hours, then poured into 450 ml of water. The resulting precipitate was filtered off and recrystallized from methanol-water 2: 1. 2-piperidine-4-amino-6-chloropyrimidine melting at 155-157 ° was obtained. Example II. To a solution of 16.4 g of 2,6-dichloro-4-amino-pyrimidine in 60 ml of benzene, a solution of 4.5 g of dimethylamine and 6 g of trimethylamine in 70 ml of benzene was added dropwise at 50-60 ° C. ¬ zenu. The mixture was heated for 3 hours at 60-70 °, then the solvent and excess trimethylamine were distilled off, and the residue was recrystallized from a 1: 1 methanol-water mixture. There was obtained 2-dimethylamino-4-amino-6-chloropyrimidine, m.p. 154-156 °. Example III. 25 g of morpholine was added to a solution of 16.4 g of 2,6-dichloro-4-aminopyrimidine in 30 ml of ethanol, and the mixture was heated at 70 ° for 1 hour. Then 150 ml of water was added and the resulting precipitate was recrystallized from methanol. 2-morpholino-4-amino-6-chloropyrimidine, mp 156-158 °, was obtained. 5933159331 Example IV. A solution of 10 g of methylamine in 40 ml of benzene was added dropwise to a solution of 16.4 g of 2,6-dichloro-4-aminopyrimidine in 50 ml of ethanol. The mixture was kept at 20 ° for an hour and then for 2 hours. at 40 ° -50 °. After the solvents have been distilled off, the residue is washed with water and recrystallized from ethanol. 2-Methylamino-4-amino-6-chloropyrimidine, mp 208-210 °, was obtained. PL
Claims (1)
Publications (1)
| Publication Number | Publication Date |
|---|---|
| PL59331B1 true PL59331B1 (en) | 1969-12-29 |
Family
ID=
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US3272811A (en) | Dihydrothieno-[3, 4-d]-pyrimidines | |
| DK150142B (en) | METHOD OF ANALOGUE FOR THE PREPARATION OF 5- (2-IMIDAZOLIN-2-YL) -AMINOPYRIMIDINES OR ACID ADDITION SALTS. | |
| AU2005225471A1 (en) | Inhibitors of histone deacetylase | |
| ZA200401365B (en) | Novel dihydropteridinones, method for producing the same and the use thereof as medicaments. | |
| JPS6056143B2 (en) | Amidine derivatives and their production method | |
| EP0055583A1 (en) | Antihypertensives | |
| CZ207892A3 (en) | Novel derivatives of triazolepyrimidine, process of their preparation and pharmaceutical mixtures in which said derivatives are comprised | |
| Garratt et al. | One-carbon compounds as synthetic intermediates. The synthesis of hydropyrimidines and hydroquinazolines by sequential nucleophilic addition to diphenyl cyanocarbonimidate with concomitant cyclization | |
| Ashley et al. | 876. The search for chemotherapeutic amidines. Part XVI. Amidinoanilino-1, 3, 5-triazines and related compounds | |
| TAYLOR et al. | The Reaction of Nitriles with o-Aminonitriles: A Convenient Synthesis of Fused 4-Aminopyrimidines1a, b | |
| JP2017513888A (en) | Novel process for producing triazine, pyrimidine and pyridine derivatives | |
| Cho et al. | Synthesis of 4-unsubstituted dihydropyrimidines. Nucleophilic substitution at position-2 of dihydropyrimidines | |
| AU9748498A (en) | 3-substituted tetrahydropyridopyrimidinone derivatives, method for producing the same, and their use | |
| US4638075A (en) | Herbicidal sulfonamides | |
| US4650892A (en) | Process for the preparation of herbicidal sulfonamides | |
| EP0144730B1 (en) | 2-anilino-1,6-dihydro-6-oxo-5-pyrimidinecarboxylic acid derivatives, processes for the preparation thereof, and antiallergic agent containing the same | |
| NO134421B (en) | ||
| PL59331B1 (en) | ||
| Akbarzadeh et al. | Synthesis of dihydrobenzo [b] pyrimido [4, 5-e][1, 4] thiazepines; derivatives of a novel ring system | |
| CA1185972A (en) | Nicotinic acid derivatives | |
| US3398155A (en) | 2, 6-dichloro-isonicotinamide derivatives and a method for their preparation | |
| US3505332A (en) | Certain 5-phenyl-2,4,7-triaminopyrido(2,3-d)pyrimidines | |
| Moustafa et al. | Utility of bis (methylthio) methylene malononitrile as a synthon in the synthesis of new poly-functionalized cyanoiminopyrimidines | |
| Kobayashi et al. | A simple method for the preparation of pyrimido [4, 5-d] pyrimidine-2, 4 (1 H, 3 H)-dithione derivatives | |
| US3320272A (en) | Process for preparing z-alkoxycyclo- heptimidazole derivatives |