SU609465A3 - Method of obtaining benzylpyrimidine derivatives or salts thereof - Google Patents

Method of obtaining benzylpyrimidine derivatives or salts thereof

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SU609465A3
SU609465A3 SU752145937A SU2145937A SU609465A3 SU 609465 A3 SU609465 A3 SU 609465A3 SU 752145937 A SU752145937 A SU 752145937A SU 2145937 A SU2145937 A SU 2145937A SU 609465 A3 SU609465 A3 SU 609465A3
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diamino
amino
carbon atoms
pyrimidine
dimethoxybenzyl
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SU752145937A
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Russian (ru)
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Компис Иван
Рей-Баллет Жеральд
Цанетти Гуйдо
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Ф.Гоффманн - Ля Рош, И Ко Аг, (Фирма)
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    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
    • C07D207/32—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C07D207/325—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms with substituted hydrocarbon radicals directly attached to the ring nitrogen atom
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    • C07C255/00—Carboxylic acid nitriles
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
    • C07D207/32—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
    • C07D207/32—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C07D207/325—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms with substituted hydrocarbon radicals directly attached to the ring nitrogen atom
    • C07D207/327—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/48—Two nitrogen atoms
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/48—Two nitrogen atoms
    • C07D239/49—Two nitrogen atoms with an aralkyl radical, or substituted aralkyl radical, attached in position 5, e.g. trimethoprim
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
    • C07D295/14—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D295/155—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings

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  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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  • Pharmacology & Pharmacy (AREA)
  • Communicable Diseases (AREA)
  • Animal Behavior & Ethology (AREA)
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  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Pyrrole Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)

Claims (2)

Изобретение относитс  к способу получени  новых производных бензилпиримидина , которые могут найти при:менение в медицине, Известна реакци  восстановлени  галогензамещенных соединений водород в момент вьщелени  ij . С целью синтеза производных пири мидина, обладающих ценными фармаколо гическими свойствами, предлагаетс  способ получени  производных бенэилпи римидина общей формулы -кНг (I) где Ti и R - алкил с 1-3 атомами углерода, алкоксигруппа с 1-3 атомами углерода; Z- амине -, пиррологруппа, группа формул NHR , NCnn,, NHR , NRCOOB, где алкш. с 1-3 атомами Углерода,. R - алканоилгруппа с 1-4 атомами углерода. или их солей, основанный на изестной реакции и зак.пючающийс  в том, то соединение общей формулы ен,-/ цНг (11) где X- хлор или бром; тг, R и Z имеют указанные значени ; восстана ливают водородом в момент выделени  с последующим выделением целевого продукта в виде основани  или его соли. В качестве восстановител  лучше использовать системы цинк - лед на  уксусна  кислота, амальгамированный цинк - натровый щелок, Алкил с 1-3 атомами углерода - метил, этил, пропил, изопропил Среди этих соединений предпочтительными  вл ютс  те, где Т и метокси- и этоксигруппа ... Замещение брома или хлора, помимо казанного способа с использованием водорода в момент ввделени  с помощью систем цинк- лед на  уксусна  или еилальгамированной цинк-натровый щелок , может быть проведено путем об работки йбдистым водородом или каталитическим гидрировамиек, например, в присутствии паллали  в спирте. Дл  получени КИСлотно-аддитивных солей, в частности солей, примен емых в фармацевтических препаратах, исполь зуют неорганические кислоты, например сол ную, серную, фосфорную, или орга йические Кислоты например, муравьи«у уксусную,  нтарную, молочную, пкыонну малеиновую, фумароЬую, винную, метансульфоновую , ft -толуолсульфоновую. i Пример 1. в раствор 1,5 г i,4-диамино-5-(4-амино-З,5-диметоксиОензил )-6-хлорпирймидина в 15,5 мл л е Д ной уксусной кислоты добавл ют рас т Эор 0,1 г хлористой ртути (2+) в 2 мл воды и 1,5 г порошкового цинка, . затем в течение ночи кип т т с обрах ным холодильником при перемешивании. На следук ций день фильтруют в гор чем виде, на фильтре ггинк промывают 5, мл уксусной кислоты, объединенные филы раты при перемешивании по капл м добавл ют при температуре ниже 20 С к 40 мл концектрированного аммиака. Затем еще 1 ч размешивают при 20®С, твердый продукт отфильтровывают на нутче, промывают водой, высушивают и перекристаллизовывают из мeтaнoлa получа  0,95 г (71%) 2,4-днамино-5- (4-амино-З,5-диметоксибензил)-пиримидина , т. пл. 214с. Получение 2,4-диаМино-5-(4-амино-3 ,5-диметокси бен зил)-б-хлорпиримидина . А. К 138 г 4-амино-З,5-диметокси- оС - (мётилсульфонйл)-метил}-бензи лового спирта в 250 мл диметилсульфок сиде добавл ют 9,75 г амида натри , перемешивают 1,25 ч при комнатной температуре, затем выливают в 2 л во ды. Образовавшийс  осадок экстрагируют этилацетатсм (2 л), зтилацетатные фазы промывают водой ( л) до отсутстви  ионов хлора, высушивают над сульфатом магни , фильтруют ив вакууме упаривают досуха. Кристалли-ческий остаток раствор ют в гор чем виде в 250 мл метилового спирта, в раствор добавл ют 150 мл воды и 18 ч выдерживают при 4 С. Выкристаллизовaвшиfic V 4-амино-З,5-диметоксибензальдегид отсасывают, прсалывают до .Отсутстви  ионов затора смесью из 40 м метилового спирта и 20 мл воды и вы . сушивают в вакууме; выход 73 г (80,7%), т.пл. 90-93 С. Б. Смесь 18,1 г Полученного в п.А соединени , 11,3 г этилового эфира циануксусной кислоты и 3 капель пиперидина нагревают 1 ч в открытом сосуд до 120 С.-Остаток перекристаллизовывают из этилацетата-петролейного эфира , получа  23 г (83,5%) этилового эфира 4-амино- d- -циан-3,5-диметокси коричной кислоты, т.пл. 134-13б С. В. 13,8 г полученного в п. S эфира Гидрируют в 500 мл этанола в присутствии 3 г паллади  на угле при комнатной температуре и 1 ати« По поглощении теоретического количества водорода реакцию прекращают. Катализатор отдел ют , фильтрат упаривают в вакууме, остаток хроматографически очищают. Выдел ют 10,8 г (78%) этилового эфира 4тамино- -циай-3,5-диметоксиГидрокоричной -кислоты, т.пл. 77-78®С (из бтилацетата-петролейного эфира). Г. В раствор 1,15 г натри  в 50 мл этанола добавл ют 13,9 г полученного а п.в эфира и раствор, полученный из 1,15 г натри  в 50 мл этанола и 5 г г уанидин-гидрохлорида, 1 ч размешивают с обратным холодильником, упаривают дрсуха, остаток раствор ют в небольшом количестве воды, фильтруют, уксусной кислотой довод т до слабокис- лой реакции, бикарбонатом натри -- до щелочной реакции, отфильтровывают на нутче и выдел ют 10,2 г (70%) 2,6Диамкно-5- (4-амино-З , 5-диметоксибензил )-4|-.пиршлйдинола, т.пл. 267-269 С (из этанола-воды).; Д. К 2,9 г полученного в п.Г соединени  в 15 мл фосфороксихлорида при перемешивании по капл м добавл ют 2,5 г диметиланилина, смесь в,течение 1 ч довод т до те{ 1пературы ки Ьени  и 4 ч кип т т с обратиьм холодильником . 8,9 мл фосфороксихлорич да отгон ют при пониженном давлении, остаток при перемешивании выливают на 80 г льда, 6 дней выдерживают при комнатной температуре, затем порци ми добавл ют 35 мл аммиака (концентрированного ) , 2 ч выдерживают, твердый продукт отфильтровывают на нутче, высушивают и перекристаллизовывают из диметилформамида-эфира, получа  1,9 (62%) 2,4-диамино-5-(4-амино-З,5-ди метоксибензил)-6-клорпирймидина, т.пл. 222-224 С. Пример 2. Аналогично примеру 1 из 3,4 г 2,4-диамино-5-(4-диме иламино-3 ,5-диметоксибензил)-б-хлорпиримидина получают 2,24 г (74%) 2,4-диамино-5- (4-диметиламино-З,5-димётоксибенз .ил)-пиримидина, т.пл. 218-219 С (из метанола). Пример 3. Аналогично примеру 1 из 3,24 г 2,4-диамино-5-(4-метиламино-3 ,5-диметокси5аизил)-6-хлорпиримидина получают 1 г (72,5%) 2,4-диамино-5-С4-метиламино-3 ,5-диметоксибензил ) -пиримидина, т.пл. 204 С (из этанола) . Пример 4. Аналогично пркмеру 1 из 3,96 г 2,4-диамино-5-(4-этоксикарбонилМетиламино 3 ,5-диметоксибензил ) -6-х л орпи римидина получают 2,75 г (76%) 2,4-диамино-5-(4-этоксикарбонилметиламино-3 ,5-диметоксибензил ) -пиримидина, т.пл. 187-188®С Диз этанола). П р и м е р 5. Аналогично примеру 1 из 3,25г 2,4-Диамино-5-(4-ацетамино-3 ,5-диметоксибензил -6 хлорпиримидина получают 2,57 г (81%) (2,4 -диамино-5- (4-ацетамино-3,5-диметоксмбензил )-пиримидина, т.пл. 278-279 С Пример 6. Аналогично примеру ). из 3,6 г 2,4-диaминo-5-(Зt5-Яимeтol«:и-4-пиppoлoбeнзил )-6-xлppпиpимиди псхпучают 2,67 г (82%) 2,4-диамйно-5- (3,5-диметокси-4-пирролобензил)-пйри 1|«идина, т.пл. , П р и м е р 7. Аналогично примеру t из 2,78 г 2,4-диамино-5-(4-г1Мино-3 ,5-диметилбеизил)-6-хлорпиримидина получают 1,65 г (68%) 2,4-диамино-5- (4-амино-3,5-диметил ензил )-пиримиди на, т.пл. 258-260 0. Формула изобретени  1. Способ получени  производных бeнэилпиpиWдинa общей формулы .1 ЙНг{ ННг где R и I - алкил с 1-3 атомами углерода, алкоксигруппа с 1-3 атомами углерода; 6 5 , 2- амино-, пиррологруппа, группа формул IHR/ , N(.R)a , NHR , где - алкил с 1-3 атомами углерода, 1И - алканоилгруппа с , 1-4 атомами углерода, или их солей, о т л и ч-а ю щ и йс   тем, что соединение общей формуN -«Нг (п) где X - хлор или бром, Н , К , Z -имеют указанные значени , восстанавливают водородом в мсжент выделени  с последующим выделением целевого продукта в свободном виде или в виде .его соли. The invention relates to a process for the preparation of new benzylpyrimidine derivatives, which can be found in: medicine. The reduction of halogen-substituted compounds to hydrogen is known at the time of separation ij. In order to synthesize pyrimidine derivatives with valuable pharmacological properties, a method is proposed for preparing benelyl pyrimidine derivatives of the general formula: kNg (I) where Ti and R are alkyl with 1-3 carbon atoms, alkoxy group with 1-3 carbon atoms; Z-amine -, pyrrologroup, group of formulas NHR, NCnn ,, NHR, NRCOOB, where alksh. with 1-3 carbon atoms ,. R is an alkanoyl group with 1-4 carbon atoms. or their salts, based on an known reaction and the order in which is a compound of the general formula ene, - / cNg (11) where X is chlorine or bromine; n, R and Z have the indicated meanings; Hydrogen is reduced at the time of isolation, followed by isolation of the desired product as a base or its salt. As a reducing agent, it is better to use the systems zinc - ice for acetic acid, amalgamated zinc - sodium hydroxide, Alkyl with 1-3 carbon atoms - methyl, ethyl, propyl, isopropyl. Among these compounds, those with T and methoxy- and ethoxy-groups are preferable. .. The substitution of bromine or chlorine, in addition to the method described above, using hydrogen at the time of introducing zinc-ice into acetic acid or electrolyzed zinc-sodium liquor using systems, can be carried out by treating it with hydrogen or catalytic hydri Miyoko, e.g., in the presence Pallanne alcohol. For the preparation of acid additive salts, in particular salts used in pharmaceutical preparations, inorganic acids are used, for example, hydrochloric, sulfuric, phosphoric, or organic acids, for example, ants in acetic, amber, dairy, pyrene maleic, fumaric, wine, methane sulfonic, ft-toluene sulfonic. i Example 1. To a solution of 1.5 g of i, 4-diamino-5- (4-amino-3, 5-dimethoxyOenzyl) -6-chloropyrmidine in 15.5 ml of acetic acid, add Eor 0 , 1 g of mercury chloride (2+) in 2 ml of water and 1.5 g of powdered zinc,. then boil overnight with an enclosed refrigerator with stirring. On the next day, it is filtered in a hot form, on the filter the wash is washed with 5, ml of acetic acid, the combined filtrates are added dropwise with stirring at a temperature below 20 ° C to 40 ml of concentrated ammonia. Then it is stirred for 1 hour at 20 ° C, the solid product is filtered off under suction, washed with water, dried and recrystallized from methanol to obtain 0.95 g (71%) of 2,4-dinamino-5- (4-amino-3, 5- dimethoxybenzyl) -pyrimidine, so pl. 214s. Preparation of 2,4-diamino-5- (4-amino-3, 5-dimethoxy benzyl) -b-chloropyrimidine. A. To 138 g of 4-amino-3, 5-dimethoxy-oC - (methylsulfonyl) -methyl} -benzyl alcohol in 250 ml of dimethyl sulfone, add 9.75 g of sodium amide, stir for 1.25 hours at room temperature, then poured into 2 liters of water. The resulting precipitate is extracted with ethyl acetate (2 L), the ethyl acetate phases are washed with water (L) until no chlorine ions are present, dried over magnesium sulfate, filtered, and evaporated in vacuo to dryness. The crystalline residue is dissolved in a hot form in 250 ml of methyl alcohol, 150 ml of water are added to the solution and kept at 4 ° C for 18 hours. The crystallization of 4 V-4-amino-3, 5-dimethoxybenzaldehyde is sucked off, and pressed to a mixture of ions. a mixture of 40 m of methyl alcohol and 20 ml of water and you. dried in vacuum; yield 73 g (80.7%), so pl. 90-93 C. B. A mixture of 18.1 g of the compound obtained in item A, 11.3 g of ethyl cyanoacetate and 3 drops of piperidine are heated for 1 hour in an open vessel to 120 C. The residue is recrystallized from ethyl acetate-petroleum ether, obtaining 23 g (83.5%) of ethyl 4-amino-d-β-cyan-3,5-dimethoxy cinnamic acid, m.p. 134-13b C. Century. 13.8 g of the ester obtained in S is hydrogenated in 500 ml of ethanol in the presence of 3 g of palladium on coal at room temperature and 1 atom. After the theoretical amount of hydrogen is absorbed, the reaction is stopped. The catalyst is separated, the filtrate is evaporated in vacuo, the residue is chromatographically purified. 10.8 g (78%) of ethyl 4-ti-cyai-3,5-dimethoxy-hydroxy-1-acid ethyl ester were isolated, m.p. 77-78®C (from petyl acetate-ethyl acetate). D. To a solution of 1.15 g of sodium in 50 ml of ethanol, 13.9 g of the obtained aa p in ether and a solution obtained from 1.15 g of sodium in 50 ml of ethanol and 5 g of uanidine hydrochloride are added, stirring for 1 h. under reflux, evaporated to dryness, the residue is dissolved in a small amount of water, filtered, adjusted to slightly acid with acetic acid, sodium bicarbonate to alkaline, filtered off under suction and 10.2 g (70%) is isolated , 6 Diamon-5- (4-amino-3, 5-dimethoxybenzyl) -4 | -.pirschledinol, m.p. 267-269 C (from ethanol-water) .; D. To 2.9 g of the compound obtained in p. G in 15 ml of phosphorus oxychloride, 2.5 g of dimethylaniline are added dropwise with stirring, the mixture is brought to the temperature of 1 h and the mixture is boiled for 1 h. with reversible fridge. 8.9 ml of phosphorus oxychloride is distilled off under reduced pressure, the residue is poured onto 80 g of ice with stirring, kept at room temperature for 6 days, then 35 ml of ammonia (concentrated) are added in portions, 2 hours are kept, dried and recrystallized from dimethylformamide ester to obtain 1.9 (62%) of 2,4-diamino-5- (4-amino-3, 5-di-methoxybenzyl) -6-chloropyrmidine, m.p. 222-224 C. Example 2. Analogously to example 1, from 3.4 g of 2,4-diamino-5- (4-dime-ylamino-3, 5-dimethoxybenzyl) -b-chloropyrimidine, 2.24 g (74%) 2 are obtained , 4-diamino-5- (4-dimethylamino-3, 5-dimethoxybenz.yl) -pyrimidine, so pl. 218-219 C (from methanol). Example 3. Analogously to example 1, from 3.24 g of 2,4-diamino-5- (4-methylamino-3, 5-dimethoxy-5-isyl) -6-chloropyrimidine, 1 g (72.5%) of 2,4-diamino-5 is obtained -C4-methylamino-3, 5-dimethoxybenzyl) -pyrimidine, m.p. 204 C (from ethanol). Example 4. Similarly, Prcmer 1 from 3.96 g of 2,4-diamino-5- (4-ethoxycarbonylMethylamino 3, 5-dimethoxybenzyl) -6-x l orpyrimidine gives 2.75 g (76%) of 2,4-diamino -5- (4-ethoxycarbonylmethylamino-3, 5-dimethoxybenzyl) -pyrimidine, m.p. 187-188® With Distil Ethanol). EXAMPLE 5. Similar to Example 1, from 3.25 g of 2,4-diamino-5- (4-acetamino-3, 5-dimethoxybenzyl-6 chloropyrimidine, 2.57 g (81%) are obtained (2.4 - diamino-5- (4-acetamino-3,5-dimethoxmbenzyl) -pyrimidine, mp 278-279 C Example 6. Analogously to the example) from 3.6 g of 2,4-diamino-5- (Zt5-Yaimetol ": And-4-pypropolobenzyl) -6-hlpppirimidi pshchuchaet 2.67 g (82%) 2,4-diamine-5- (3,5-dimethoxy-4-pyrrolobenzyl) -pry 1 |" idina, tpl ., Example 7: Analogously to example t, from 2.78 g of 2,4-diamino-5- (4-g1Mino-3, 5-dimethylbeizyl) -6-chloropyrimidine, 1.65 g (68%) are obtained 2,4-diamino-5- (4-amino-3,5-dimethyl enzyl) -pyrimidine, mp 258-260 0. Claims 1. allowance for the derivatization of benabylpyridine of the general formula .1 IHg {HHg where R and I are alkyl with 1-3 carbon atoms, alkoxy group with 1-3 carbon atoms; 6 5, 2-amino, pyrrologroup, group of formulas IHR /, N (. R) a, NHR, where is alkyl with 1-3 carbon atoms, 1I is alkanoyl group, 1-4 carbon atoms, or their salts, o tl and h-and y and yc by the fact that the compound of the general formN is " Hg (p) where X is chlorine or bromine, H, K, Z has the indicated values, is reduced by hydrogen to extract gas, followed by isolation of the target product in free form or in the form of its salt. 2. Способ ПОП.1, отличающийс  тем, что в качестве восстановител  используют систему цинклед на  уксусна  кислота или амальгамированный цинк-натровый щелок. Источники информации, прин тые во внимание при экспертизе: 1. Вейганд-Хильгетаг. Методы эксперимента в органической химии. М,, Хими  1968,с. 70.2. Method POP.1, characterized in that a zincled system for acetic acid or amalgamated zinc-sodium liquor is used as a reducing agent. Sources of information taken into account in the examination: 1. Weigand-Hilgetag. Experimental methods in organic chemistry. M ,, Himi 1968, p. 70
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JPS5481278A (en) * 1977-10-18 1979-06-28 Wellcome Found Manufacture of triiseccaminomethane
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