SU637086A3 - Method of obtaining purine derivatives, or their acid-additive salts or alkali metal salts - Google Patents

Method of obtaining purine derivatives, or their acid-additive salts or alkali metal salts

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Publication number
SU637086A3
SU637086A3 SU772455681A SU2455681A SU637086A3 SU 637086 A3 SU637086 A3 SU 637086A3 SU 772455681 A SU772455681 A SU 772455681A SU 2455681 A SU2455681 A SU 2455681A SU 637086 A3 SU637086 A3 SU 637086A3
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USSR - Soviet Union
Prior art keywords
general formula
alkali metal
compound
hydrogen
salts
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Application number
SU772455681A
Other languages
Russian (ru)
Inventor
Джон Шаффер Ховард
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Дзе Велкам Фаундейшн Лимитед (Фирма)
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Priority claimed from GB7988/76A external-priority patent/GB1561380A/en
Application filed by Дзе Велкам Фаундейшн Лимитед (Фирма) filed Critical Дзе Велкам Фаундейшн Лимитед (Фирма)
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Publication of SU637086A3 publication Critical patent/SU637086A3/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D473/00—Heterocyclic compounds containing purine ring systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/20—Antivirals for DNA viruses
    • A61P31/22—Antivirals for DNA viruses for herpes viruses
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D473/00—Heterocyclic compounds containing purine ring systems
    • C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
    • C07D473/16—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two nitrogen atoms

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  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Virology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Oncology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Communicable Diseases (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Molecular Biology (AREA)
  • Biotechnology (AREA)
  • Engineering & Computer Science (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Description

сацию пурина общей формулы (II), где Q- водород, с соединением общей формулы (III), где А - галоид, в ирисутствии основани , например гидрида иатри .Cation of purine of the general formula (II), where Q is hydrogen, with a compound of the general formula (III), where A is halogen, in the presence of a base, for example, iatri hydride

Пример 1. Получение 9- (2-пропионоилоксиэтоксиметил )-гуанина.Example 1. The preparation of 9- (2-propionoyloxyethoxymethyl) -guanine.

A.31 2 этиленгли:кол , 18,5 г пропионовой кислоты и 7,5 г сильной ионоводородной смолы Био Род АС 50 Х-4 в 100 мл толуола орошают при перемешивании иод ловушкой Дина Старка в течение 18 ч. Затем мгновенным испарением удал ют толуол и оставшуюс  жидкость дистиллируют. За начальным головным погоном зтиленгликол  иолучают дистилл т желаемого продукта - этиленгликоль моиопропионата. Выход 70%.A.31 2 ethylene glycers: cola, 18.5 g of propionic acid and 7.5 g of Bio Rhode AC 50 X-4 strong ion hydrogen resin in 100 ml of toluene are irrigated with stirring, the iodine is trapped for 18 hours by instant evaporation. the toluene and the remaining liquid are distilled. Behind the initial head strap, the glycol glycol is distilled and the distillate of the desired product is obtained — ethylene glycol myopropionate. Yield 70%.

Б. Сухой хлористый водород иропускают в охлажденную (0°С) суспензию 7,1 г этиленгликол  монопроииопата, полученную выше, и 1,8 г параформальдегида в 50 мл дихлорметада, пока осадок не растворитс  в смеси, насыщеиной хлористым водородом . После высушивани  над молекул рными ситам.и и хлоридом кальци  смесь отфильтровывают и растворитель удал ют мгиовенным выпариванием при 30° С. Оставшеес  масло 2-пропионоилоксиэтоксиметилхлорида используют далее непосредственно . Выход 60%.B. Dry hydrogen chloride is sprinkled into a cooled (0 ° C) suspension of 7.1 g of ethylene glycol monopropane prepared above and 1.8 g of paraformaldehyde in 50 ml of dichloromethane until the residue dissolves in a mixture saturated with hydrogen chloride. After drying over molecular sieves. And calcium chloride, the mixture is filtered and the solvent is removed by immediate evaporation at 30 ° C. The remaining 2-propionoyloxyethoxymethyl chloride oil is then used directly. Yield 60%.

B.2,53 г гидрида натри  в 57%-ной минеральной масл ной дисперсии промывают сухим гексаном и добавл ют к раствору 4,53 г гуанина в 100 мл сухого диметилсульфоксида , после чего смесь перемешивают при 30° С в течение 23 ч. Затем добавл ют 5,5 г 2-пропионоилоксиэтоксиметилхлорида и реакционную смесь перемешивают при 20° С в течеиие 18 ч. Раствор отфильтровывают И растворитель удал ют мгновенным выпариванием в вакууме. Остаток охлаждают на лед ной бане, раствор ют в воде и нейтрализуют уксусной кислотой. После выдерживани  в течение 1 ч продукт отфильтровывают , промывают водой и сушат. Перекристаллизацией (3 раза) из кип щего ацетонитрила получают 9-(2-пропионоилоксиэтоксиметил )-гуанин. Выход 35%, 223-226° С.B.2.53 g of sodium hydride in 57% mineral oil dispersion is washed with dry hexane and 4.53 g of guanine in 100 ml of dry dimethyl sulfoxide is added to the solution, after which the mixture is stirred at 30 ° C for 23 hours. 5.5 g of 2-propionoyloxyethoxymethyl chloride are added and the reaction mixture is stirred at 20 ° C for 18 hours. The solution is filtered and the solvent is removed by instant evaporation in vacuo. The residue is cooled in an ice bath, dissolved in water and neutralized with acetic acid. After standing for 1 hour, the product is filtered, washed with water and dried. Recrystallization (3 times) from refluxing acetonitrile gives 9- (2-propionoyloxyethoxymethyl) -guanine. Yield 35%, 223-226 ° C.

Пример 2. Получение 9- (2-додеканоилоксиэтоксиметил )-2,6-диаминопурина.Example 2. Getting 9- (2-dodecanoyl) ethoxy) -2,6-diaminopurine.

Сухой хлористый водород пропускают в охлажденную (0°С) суспензию 14,66 этилеигликольмопододеконата и 1,8 г параформальдегида в 50 мл дихлорметана, пока твердые частицы не раствор тс , а затем смесь насыщают хлористым водородом. После высушивани  раствора над молекул рными ситами и хлористым кальцием смесь отфильтровывают и растворители удал ют мгиовенным испарением при 30° С. Оставшеес  масло 2-додеканоилоксиэтоксиметилхлорида использзют далее непосредственно . Выход 75%.Dry hydrogen chloride is passed to a cooled (0 ° C) suspension of 14.66 ethylene glycol pre-dodeconate and 1.8 g of paraformaldehyde in 50 ml of dichloromethane until the solids dissolve and then the mixture is saturated with hydrogen chloride. After the solution was dried over molecular sieves and calcium chloride, the mixture was filtered and the solvents were removed by immediate evaporation at 30 ° C. The remaining 2-dodecanoyl-oxyethoxymethyl chloride oil was then used directly. 75% yield.

Безводный оаствоп 2.6-пиаминопупина RAnhydrous solution 2.6-piaminopupina R

диметилформамиде готов т нагреванием 3,54 г моногидрата в 250 мл растворител  па паровой бане до растворени , охлаждают и оставл ют сто ть дл  испарени  вdimethylformamide is prepared by heating 3.54 g of the monohydrate in a 250 ml of solvent in a steam bath until dissolved, cooled and left to stand to evaporate in

течение 18 ч.for 18 hours

К смеси добавл ют 0,95 г 57%-ной минеральной масл ной дисперсии гидрида натри . После перемешивани  сусиензии в течеиие ночи капельным путем добавл ютTo the mixture was added 0.95 g of a 57% mineral oil dispersion of sodium hydride. After stirring the suspension for overnight, add

6,35 г 2-додеканоилоксиэтокоиметилхлорида и реакционную смесь перемешивают при окружающей температуре в течение ночи. Твердые частицы отфильтровывают, промывают хлороформом, объединенные промывки и маточный раствор выпаривают при 60° С. Оставшеес  масло перекриеталлизовывают из этанола. Выход 20%.6.35 g of 2-dodecanoyl-oxo-ethomethyl chloride and the reaction mixture is stirred at ambient temperature overnight. The solids are filtered, washed with chloroform, the combined washes and the mother liquor is evaporated at 60 ° C. The remaining oil is recrystallized from ethanol. Yield 20%.

Claims (3)

1. Способ получепи  производных пурина общей формулы1. A method for obtaining purine derivatives of the general formula L L Г I «GI " iillj- O-CHa 12 o-ti-R;iillj-O-CHa 12 o-ti-R; где Ri - ОКСИ- или аминогруппа; 30R2 - водород, пр ма  или разветвленна  группа алкильной цепи Сг-С|б,where Ri - OXI - or amino group; 30R2 is hydrogen, a straight or branched chain group of the Cr – C | b alkyl chain, или их кислотноаддитнвных солей, или солей щелочных металлов,or their acid addition salts, or alkali metal salts, 35 отличающийс  тем, что соединение общей формулы35 characterized in that the compound of the general formula -ЛД./-LD / 1 1eleven Н,H, где R имеет вышеуказанные значени ;where R is as defined above; Q - атом водорода или щелочного металла,Q is a hydrogen atom or an alkali metal, подвергают взаимодействию с соединением общей формулыsubjected to interaction with the compound of the General formula А-СНг-О-СНа-СНг-О-С-Ra 1 (III)A-CHg-O-CHa-CHg-O-C-Ra 1 (III) ОABOUT где А - реакционноепособный остаток органической или неорганической кислоты;where a is the reactive residue of an organic or inorganic acid; R2 имеет вышеуказанные значени , с последующим выделением целевого продукта в виде основани  или кислотноаддитивной соли, или соли щелочного металла.R2 is as defined above, followed by isolation of the desired product as a base or acid addition salt or alkali metal salt. 2. Способ по ц. 1, отличающийс  тем, что используют соединение общей формулы (III), где А - галоид или сульфонатна  группа.2. The method according to c. 1, characterized in that a compound of the general formula (III) is used, where A is a halogen or sulphonate group. 3. Способ по пп. 1 и2, отличаю щи йс   тем. что ИСПОЛЬЗУЮТ г.оелинение обтпе.й 563. The method according to paragraphs. 1 and 2, I differ from that. that they USE the utility general. 56 формулы (II), где Q - водород, и соедине-27.08.76 при R2 - пр ма  или развегние общей формулы (П1), где А - галоид,вленна  группа алкильной цепи Сз-С.of formula (II), where Q is hydrogen, and the compound of August 27, 76 at R2 is straightforward or common, of general formula (P1), where A is halogen, a straight chain alkyl group of C3-C. и процесс провод т в присутствии основаии .Источники информации, прин тые воand the process is conducted in the presence of a base. Sources of information taken in Приоритет по признакам:1. Гетероциклические соединени  подPriority signs: 1. Heterocyclic compounds under 01.03.76 при RI - все значени ; Rg -ред. Р. Эльдерфильда. М., Мир, 1969, т. 8,03/01/76 with RI - all values; Rg -Ed. R. Elderfield. M., Mir, 1969, v. 8, водород.с. 288 и ел.hydrogen.s. 288 and ate. 637086 637086 5внимание при экспертизе:5 attention during examination:
SU772455681A 1976-03-01 1977-03-01 Method of obtaining purine derivatives, or their acid-additive salts or alkali metal salts SU637086A3 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB7988/76A GB1561380A (en) 1976-03-01 1976-03-01 Esters of hydroxyalkoxyalkyl purines their preparation and pharmaceutical compositions containing them
US71810576A 1976-08-27 1976-08-27

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SU637086A3 true SU637086A3 (en) 1978-12-05

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AR (4) AR228232A1 (en)
AT (1) AT361007B (en)
AU (1) AU515553B2 (en)
BE (1) BE851972R (en)
BG (2) BG27750A3 (en)
CA (1) CA1086316A (en)
CH (4) CH629806A5 (en)
DD (1) DD128611A5 (en)
DE (1) DE2708827A1 (en)
DK (1) DK147824C (en)
ES (1) ES456432A2 (en)
FI (1) FI60710C (en)
FR (1) FR2342972A2 (en)
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HU (1) HU176907B (en)
IE (1) IE44708B1 (en)
IT (1) IT8048953A0 (en)
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NL (2) NL7702175A (en)
PL (2) PL115242B1 (en)
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* Cited by examiner, † Cited by third party
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NL8202626A (en) * 1982-06-29 1984-01-16 Stichting Rega V Z W DERIVATIVES OF 9- (2-HYDROXYETHOXYMETHYL) GUANINE.
ES8403904A1 (en) * 1983-02-25 1984-04-01 Ind Farma Especial Process for the preparation of acycloguanosine
GB8816760D0 (en) * 1988-07-14 1988-08-17 Wellcome Found Therapeutic compounds
JP4704223B2 (en) * 2006-01-30 2011-06-15 Ｈｏｙａ株式会社 Lead screw mechanism

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JPS5122049A (en) * 1974-08-19 1976-02-21 Sanwa Denki Kk KAHENTEIKO SOCHI

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IE44708L (en) 1977-09-01
DK147824C (en) 1985-07-22
PL211568A1 (en) 1979-07-30
DE2708827C2 (en) 1989-01-12
LU76869A1 (en) 1977-09-26
CH632757A5 (en) 1982-10-29
ES456432A2 (en) 1978-07-16
HU176907B (en) 1981-05-28
FR2342972A2 (en) 1977-09-30
BG28067A3 (en) 1980-02-25
AU515553B2 (en) 1981-04-09
SE7702233L (en) 1977-09-02
NL7702175A (en) 1977-09-05
CH629806A5 (en) 1982-05-14
AU2275977A (en) 1978-09-07
AR228232A1 (en) 1983-02-15
JPS52106896A (en) 1977-09-07
ATA134877A (en) 1980-07-15
AR228281A1 (en) 1983-02-15
AR228283A1 (en) 1983-02-15
DK147824B (en) 1984-12-17
AT361007B (en) 1981-02-10
SE433216B (en) 1984-05-14
JPS635392B2 (en) 1988-02-03
ZA771220B (en) 1978-10-25
DD128611A5 (en) 1977-11-30
FI770655A (en) 1977-09-02
AR228282A1 (en) 1983-02-15
FI60710C (en) 1982-03-10
RO76591A (en) 1981-04-30
DE2708827A1 (en) 1977-09-08
PL115267B1 (en) 1981-03-31
BG27750A3 (en) 1979-12-12
IE44708B1 (en) 1982-03-10
GR66070B (en) 1981-01-15
IT8048953A0 (en) 1980-06-12
FI60710B (en) 1981-11-30
PL196356A1 (en) 1979-05-07
CA1086316A (en) 1980-09-23
BE851972R (en) 1977-09-01
CH631176A5 (en) 1982-07-30
NL8400896A (en) 1984-07-02
CH632758A5 (en) 1982-10-29
PL115242B1 (en) 1981-03-31
DK88677A (en) 1977-09-02
FR2342972B2 (en) 1980-06-27

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