CS275695B6 - Process for preparing 3-methyl-7-alkyl xanthines - Google Patents
Process for preparing 3-methyl-7-alkyl xanthines Download PDFInfo
- Publication number
- CS275695B6 CS275695B6 CS81688A CS81688A CS275695B6 CS 275695 B6 CS275695 B6 CS 275695B6 CS 81688 A CS81688 A CS 81688A CS 81688 A CS81688 A CS 81688A CS 275695 B6 CS275695 B6 CS 275695B6
- Authority
- CS
- Czechoslovakia
- Prior art keywords
- methyl
- formula
- formic acid
- alkyl
- alkali metal
- Prior art date
Links
- 238000004519 manufacturing process Methods 0.000 title abstract description 3
- 229940065721 systemic for obstructive airway disease xanthines Drugs 0.000 title 1
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims abstract description 18
- 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 abstract description 9
- 235000019253 formic acid Nutrition 0.000 claims abstract description 9
- 229910000288 alkali metal carbonate Inorganic materials 0.000 claims abstract description 5
- 150000008041 alkali metal carbonates Chemical class 0.000 claims abstract description 5
- 239000012736 aqueous medium Substances 0.000 claims abstract description 3
- 238000002360 preparation method Methods 0.000 claims abstract description 3
- 238000000034 method Methods 0.000 claims description 8
- 229910052783 alkali metal Inorganic materials 0.000 claims 1
- 150000001340 alkali metals Chemical class 0.000 claims 1
- 239000012670 alkaline solution Substances 0.000 claims 1
- 125000000217 alkyl group Chemical group 0.000 claims 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 abstract description 3
- 239000000543 intermediate Substances 0.000 abstract description 3
- 229910001854 alkali hydroxide Inorganic materials 0.000 abstract description 2
- 239000003814 drug Substances 0.000 abstract description 2
- 239000002253 acid Substances 0.000 abstract 1
- 239000004744 fabric Substances 0.000 abstract 1
- YAPQBXQYLJRXSA-UHFFFAOYSA-N theobromine Chemical compound CN1C(=O)NC(=O)C2=C1N=CN2C YAPQBXQYLJRXSA-UHFFFAOYSA-N 0.000 description 6
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- MHNVSFOURBQRPK-UHFFFAOYSA-N 3-methyl-7-propylpurine-2,6-dione Chemical compound CN1C(=O)NC(=O)C2=C1N=CN2CCC MHNVSFOURBQRPK-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 229960004559 theobromine Drugs 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- VCMTXXSJNFBMBV-UHFFFAOYSA-N 6-amino-1-methyl-5-(methylamino)pyrimidine-2,4-dione Chemical compound CNC1=C(N)N(C)C(=O)NC1=O VCMTXXSJNFBMBV-UHFFFAOYSA-N 0.000 description 1
- PXXPWRGFQVGQAZ-UHFFFAOYSA-N 6-amino-1-methyl-5-(propylamino)pyrimidine-2,4-dione Chemical compound CCCNC1=C(N)N(C)C(=O)NC1=O PXXPWRGFQVGQAZ-UHFFFAOYSA-N 0.000 description 1
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 1
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Riešenie sa týká přípravy 3-metyl-7-alkylxantínov z l-metyl-5-alkyl-amíno-6-aminouracilov vo vodnom prostředí posobením kyseliny mravčej a následné alkalického hydroxidu alebo uhličitanu alkalického kovu pri teplote 60 - 100 'C. Látky zlúžia ako medziprodukty pre výrobu liečiv.The solution relates to the preparation of 3-methyl-7-alkylxanthines from 1-methyl-5-alkyl-amino-6-aminouracils in an aqueous medium by acid formic acid and subsequent alkali hydroxide or an alkali metal carbonate at 60 - 100 ° C. Fabrics narrow as intermediates for the manufacture of medicaments.
Description
Predmetom vynálezu je sposob přípravy 3-metyl-7-alkylxantínov všeobecného vzorca IThe present invention relates to a process for the preparation of 3-methyl-7-alkylxanthines of the general formula I
kde R je lineárny alebo rozvětvený alkyl C^ až C^, ktoré sú medziprodukty pre výrobu liečiv.wherein R is linear or branched C 1 to C 4 alkyl, which are intermediates for the manufacture of medicaments.
Předmětné zlúčeniny vzorca I, kde R = CH3, sa připravili z l-metyl-5-alkylamino-6-aminouracilov vzora IIThe subject compounds of formula I, wherein R = CH 3 , were prepared from 1-methyl-5-alkylamino-6-aminouracils of formula II
(II) , kde R je CH3, refluxováním s kyselinou mravčou vo formamide (Wojciechovski Pol. 42976) vo výtažku 69 %.(II), where R is CH 3 , by refluxing with formic acid in formamide (Wojciechovski Pol. 42976) in a yield of 69%.
Postupom podía vynálezu sa předmětné zlúčeniny vzorca I pripravujú z uracilov vzorca II vo vodnom prostředí. Primárné sa na alkylaminouracil vzorca II posobí kyselinou mravčou pri zvýšenej teplote 60 až 100 *C.According to the process of the invention, the subject compounds of formula I are prepared from uracils of formula II in an aqueous medium. The alkylaminouracil of formula II is primarily treated with formic acid at an elevated temperature of 60-100 ° C.
Používá sa molárny poměr kyseliny mravčej ku alkylaminouracilu vzorca II 1 : 1 až 1:2. Následné sa na vzniklý medziprodukt posobí alkalickým hydroxidom alebo uhličitanom alkalického kovu pri teplote 60 až 100 'c a molárnom pomere alkalického lúhu alebo uhličitanu alkalického kovu k alkylaminouracilu vzorca II 1 : 1 až 1,5 : 1.A molar ratio of formic acid to alkylaminouracil of formula II of 1: 1 to 1: 2 is used. Subsequently, the resulting intermediate is treated with an alkali metal hydroxide or alkali metal carbonate at a temperature of 60 to 100 ° C and a molar ratio of alkali hydroxide or alkali metal carbonate to alkylaminouracil of formula II of 1: 1 to 1.5: 1.
Postup podía vynálezu je výhodný v tom, že sa reakcia uskutočňuje pri podstatné nižšej teplote (60 až 100 ‘c oproti 180 ’C pri formamide), 3alej nie je potřebné používat organické rozpúštadlo formamid, stačí použit přibližné ekvimolárne množstvo kyseliny mravčej vo vodnom prostředí.The process according to the invention is advantageous in that the reaction is carried out at a substantially lower temperature (60 to 100 ° C versus 180 ° C for formamide).
V dalšom je predmet vynálezu objasněný v príkladoch bez toho, aby sa na tieto výlučné obmedzoval. ’In the following, the subject matter of the invention is illustrated in the examples without being limited thereto. ’
Příklad 1Example 1
3-metyl-7-metylxantín3-methyl-7-methylxanthine
Zmes 4,5 g l-metyl-5-metylamino-6-aminouracilu, 1,09 ml kyseliny mravčej a 15 ml vody sa zahrieva za refluxu 0,5 hodiny. Následné sa přidá 1,2 g hydroxidu sodného, pokračuje sa v zahrievaní dalšiu 0,5 hodiny. Reakčná zmes sa za horúca odfarbí aktívnym uhlím, přefiltruje a okyslí kyselinou octovou. Vylúčená zrazenina sa odfiltruje a vysuší. Získá sa 4,6 g teobromínu s t. t. 341 až 344 'C.A mixture of 4.5 g of 1-methyl-5-methylamino-6-aminouracil, 1.09 ml of formic acid and 15 ml of water is heated under reflux for 0.5 hour. Subsequently, 1.2 g of sodium hydroxide are added, heating is continued for a further 0.5 hour. The reaction mixture is decolorized while hot with activated charcoal, filtered and acidified with acetic acid. The precipitate formed is filtered off and dried. 4.6 g of theobromine with m.p. t. 341 to 344 ° C.
3-mety1-7-n-propylxantín3-methyl-7-n-propylxanthine
Zmes 61,5 g l-metyl-5-propylamino-6-aminouracilu, 150 mg kyseliny mravčej a 50 ml vody sa refluxuje počas 1 hodiny. Vylúčená zrazenina sa odfiltruje a vloží do 350 ml 10%ného roztoku hydroxidu draselného, kde sa refluxuje ešte 4 hodiny. Opravou hodnoty pH sa 4 sa získá 41 g 3-metyl-7-n-propylxantínu s t. t. 256 až 261 ‘c.A mixture of 61.5 g of 1-methyl-5-propylamino-6-aminouracil, 150 mg of formic acid and 50 ml of water is refluxed for 1 hour. The precipitate formed is filtered off and taken up in 350 ml of 10% potassium hydroxide solution, where it is refluxed for a further 4 hours. The pH was adjusted to 4 to give 41 g of 3-methyl-7-n-propylxanthine, m.p. t. 256 to 261 ‘c.
Příklad 3Example 3
3-mety1-7-metyIxantín3-methyl-7-methylxanthine
Analogicky postupu uvedenému v příklade 1 s tým, že sa použije nasýtený roztok hydrogénuhličitanu sodného (10 ml), sa získá 4,8 g teobromínu s t. t. 341 až 344 c.In analogy to the procedure of Example 1, using saturated sodium bicarbonate solution (10 ml), 4.8 g of theobromine with m.p. t. 341 to 344 c.
Příklad 2Example 2
Claims (4)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CS81688A CS275695B6 (en) | 1988-02-10 | 1988-02-10 | Process for preparing 3-methyl-7-alkyl xanthines |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CS81688A CS275695B6 (en) | 1988-02-10 | 1988-02-10 | Process for preparing 3-methyl-7-alkyl xanthines |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CS8800816A1 CS8800816A1 (en) | 1989-04-14 |
| CS275695B6 true CS275695B6 (en) | 1992-03-18 |
Family
ID=5341019
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS81688A CS275695B6 (en) | 1988-02-10 | 1988-02-10 | Process for preparing 3-methyl-7-alkyl xanthines |
Country Status (1)
| Country | Link |
|---|---|
| CS (1) | CS275695B6 (en) |
-
1988
- 1988-02-10 CS CS81688A patent/CS275695B6/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| CS8800816A1 (en) | 1989-04-14 |
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