LV14663B - Synthesis of pyrrolo[1,2-a]quinazoline derivatives from anthranilic acid hydrazides and alfa-ketoacids - Google Patents
Synthesis of pyrrolo[1,2-a]quinazoline derivatives from anthranilic acid hydrazides and alfa-ketoacids Download PDFInfo
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- LV14663B LV14663B LVP-13-26A LV130026A LV14663B LV 14663 B LV14663 B LV 14663B LV 130026 A LV130026 A LV 130026A LV 14663 B LV14663 B LV 14663B
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Izgudrojums attiecas uz bioorganiskās ķīmijas nozari, konkrēti, pirolo[l,2ajhinazolīna atvasinājumu sintēzi.The invention relates to the field of bioorganic chemistry, in particular to the synthesis of pyrrolo [1,2-quinazoline derivatives.
Kondensēti hinazolīna atvasinājumi ietilpst gan dabas vielu, gan sintētisku farmaceitisku preparātu sastāvā. Vieni no šāda tipa savienojumiem - pirolo[l,2aļhinazolīni ir alkaloīda peganīna (Peganine) struktūras izomēri [1]. Pētot šos savienojumus, atklātas vielas ar analgezējošu [2], antihipertensīvu [3] iedarbību un centrālo nervu sistēmu nomierinošām īpašībām [4],Condensed quinazoline derivatives are part of both natural substances and synthetic pharmaceuticals. One such type of compound, pyrrolo [1,2-a] quinazolines, is a structural isomer of the alkaloid peganine (Peganine) [1]. Investigations of these compounds have revealed analgesic [2], antihypertensive [3] and central nervous system sedative properties [4],
Klasiska pirolo[l,2-a]hinazolīnu iegūšanas metode ir 2-aminobenzoskābes esteru vai nitrilu alkilēšana ar 4-halogēnbutānnitrila atvasinājumiem [5]. Zināma ari retāk lietojama metode , konkrēti, 2-aminobenzoskābes ( antranilskābes) amīdu (AA) reakcija ar a-ketoskābēm [6,7] (pieņemts par prototipu). Pēc prototipa metodes var iegūt N-H vai N-alkil pirolo[l,2-a]hinazolīna atvasinājumus, no kuriem izveidot savienojumus ar N-N saiti praktiski nav iespējams.A classic method for the preparation of pyrrolo [1,2-a] quinazolines is the alkylation of 2-aminobenzoic acid esters or nitriles with 4-halobutanenitrile derivatives [5]. A less commonly used method, in particular the reaction of 2-aminobenzoic acid (anthranilic acid) amides (AA) with α-ketoic acids [6,7] (assumed as a prototype). The prototype method provides N-H or N-alkyl pyrrolo [1,2-a] quinazoline derivatives from which it is practically impossible to form a N-N bond.
Izgudrojuma autori piedāvā pirolo[l,2-a]hinazolīnu sintēzes metodi, izmantojot antranilskābes hidrazīdu (AH) reakciju ar α-ketoskābēm, kuru rezultātā iegūst pirolo[l,2-a]hinazolīna atvasinājumus, kas satur vienu slāpekļa atomu vairāk un jau sintēzes procesā veidojas N-N saite. Līdz ar to piedāvātā metode ļauj iegūt jaunus Nacilaminoatvasinājumus.The present inventors propose a process for the synthesis of pyrrolo [1,2-a] quinazolines by reaction of anthranilic acid hydrazides (AH) with α-ketoic acids to give pyrrolo [1,2-a] quinazoline derivatives containing one nitrogen atom more and already synthesizing them. an NN link is formed in the process. Thus, the proposed method allows the preparation of new Nacylamino derivatives.
Antranilskābes amidsAnthranilic acid amide
Antranilskābes hidrazidsAnthranilic acid hydrazide
R - aizvietotājsR is a substituent
Par izejvielām pirolo[l,2-a]hinazolīnu 6, 7 iegūšanai izmantojām literatūrā zināmos 2-/V-acilantranilhidrazīdus 3a-e, kurus sintezējām no izatskābes anhidrida (1) un benzoskābes, m-brombenzoskābes, salicilskābes, nikotīnskābes un izonikotīnskābes hidrazīdiem (2a-e) dimetilformamīda šķīdumā trietilamīna klātbūtnē pēc aprakstītas metodes [8].The starting materials for the preparation of pyrrolo [1,2-a] quinazolines 6, 7 were the literature 2- (N-acylanthranilhydrazides 3a-e) synthesized from the anhydride (1) and benzoic, m-bromobenzoic, salicylic, hydric and 2a-e) in dimethylformamide solution in the presence of triethylamine according to the method described [8].
2-V-acilantranilhidrazīdu 3a-e reakcijās ar 2-oksoglutārskābi (4) vai 4oksopentānskābi (levulīnskābi) (5) ledus etiķskābes šķīdumā iegūti attiecīgie pirolo[l,2aļhinazolīna atvasinājumi (6,7)ar augstiem iznākumiem (71-85%).Reactions of 2-N-acylanthranilhydrazide 3a-e with 2-oxoglutaric acid (4) or 4-oxopentanoic acid (levulinic acid) (5) in glacial acetic acid solution yielded the corresponding pyrrolo [1,2a] quinazoline derivatives (6,7) with high yields (71-85).
Br HOBr HO
Jāatzīmē, ka tieši šādu izejvielu pielietošanas rezultātā iegūstam papildus pozitīvus momentus. Pirmkārt, hidrazīdu 3a-e izmantošanas rezultātā mērķsavienojumi 6, 7 satur struktūras fragmentu CO-N-N. Bioloģisko pētījumu dati liecina, ka šāds elementu izvietojums parasti piemīt savienojumiem ar analgētisku un pretiekaisuma aktivitāti [9].It should be noted that the use of such raw materials results in additional positive moments. First, as a result of the use of hydrazides 3a-e, the target compounds 6, 7 contain the moiety CO-N-N. Biological studies have shown that this elemental arrangement is typically found in compounds with analgesic and anti-inflammatory activity [9].
Otrkārt, a-oksoglutārkābes (4) un levulīnskābes (5) lietošana ļauj ievadīt gala produkta molekulā -COOH vai -CH3 funkcionālu grupu, kas nodrošina, galvenokārt karboksilgrupas gadījumā, molekulas tālākas modifikācijas iespējas.Secondly, the use of α-oxoglutaric acid (4) and levulinic acid (5) allows the introduction into the final product of a -COOH or -CH3 functional group which provides further modifications of the molecule, mainly in the case of the carboxyl group.
Vispārīgā procedūra 1 4-aciIamino-l,5-diokso-l,233a,4,5-heksahidropirolo[l,2a]hinazolīn-3a-karbonskābju 6a-e iegūšanai:General procedure for the preparation of 14-acylamino-1,5-dioxo-1,2,33a, 4,5-hexahydropyrrolo [1,2a] quinazoline-3a-carboxylic acids 6a-e:
0,001 mol TV-acilantranilhidrazīda 3a-e un 0,0012 mol 2-oksoglutārskābes (4) vāra 3 ml ledus etiķskābes. Kad izveidojušās nogulsnes (6b un 6e - 5 min.; 6a - 30 min.), vārīšanu pārtrauc un iztur istabas temperatūrā ~3 stundas, tad filtrē, žāvē un pārkristalizē. Ja nogulsnes neveidojas (6c un 6d), vāra 3 stundas, tad atdzesē un atstāj uz 20 stundām istabas temperatūrā. Nogulsnes filtrē, žāvē un pārkristalizē.0.001 mol TV-acylanthranilhydrazide 3a-e and 0.0012 mol 2-oxoglutaric acid (4) are boiled in 3 ml glacial acetic acid. When a precipitate has formed (6b and 6e - 5 min; 6a - 30 min), stop cooking and keep at room temperature for ~ 3 hours, then filter, dry and recrystallize. If no precipitate forms (6c and 6d), boil for 3 hours, then cool and leave for 20 hours at room temperature. The precipitate is filtered off, dried and recrystallized.
Vispārīgā procedūra 2 4-Acilamino-3a-metil-2,3,3a,4-tetrahidropiroIo[l,2a]hinazolīn-l,S-dionu 7a-e iegūšanai:General procedure for the preparation of 2 4-Acylamino-3a-methyl-2,3,3a, 4-tetrahydropyrrolo [1,2a] quinazoline-1,5-dione 7a-e:
0,001 mol V-acilantranilhidrazīda 3a-e un 0,0012 mol 2-oksopentānskābes (5) vāra 3 ml ledus etiķskābes 4 stundas. Atdzesē, atstāj uz 20 stundām istabas temperatūrā. Pievieno ~10 ml ūdens, maisa. Izveidojušās nogulsnes 7a-c filtrē, žāvē, pārkristalizē.0.001 mol of V-acylanthranilhydrazide 3a-e and 0.0012 mol of 2-oxopentanoic acid (5) are boiled in 3 ml of glacial acetic acid for 4 hours. Leave to cool for 20 hours at room temperature. Add ~ 10 ml water, stir. The resulting precipitate 7a-c is filtered, dried, recrystallized.
Reakcijas maisījumu, kas satur 7d vai 7e, ietvaicē līdz sausam atlikumam, pievieno dietilēteri un etanolu (7d) vai heksānu (7e), tad filtrē, žāvē, pārkristalizē.Evaporate the reaction mixture containing 7d or 7e to dryness, add diethyl ether and ethanol (7d) or hexane (7e), then filter, dry, recrystallize.
1. piemērs: savienojums 6a sintezēts pēc vispārīgas procedūras 1:Example 1: Compound 6a was synthesized following the general procedure 1:
Iznākums 78% (pārkristalizēts no etanola); k.p. > 250°C.Yield: 78% (recrystallized from ethanol); p.p. > 250 ° C.
H-KMR (300 MHz, DMSOd6), δ, ppm: 2,49-2,73 (4H, m, 2CH2); 7,38 (1H, t, 7=7,5, arom.); 7,51-7,73 (4H, pl. m, arom.); 7,97 (3H, d, J-Ί,Ί, arom.); 8,21 (1H, d, J=8,l, arom.); 10,66 (1H, s, NH); 14,30 (1H, pl. s, COOH).1 H-NMR (300 MHz, DMSO d 6 ), δ, ppm: 2.49-2.73 (4H, m, 2CH 2 ); 7.38 (1H, t, J = 7.5, arom.); 7.51-7.73 (4H, m, arom.); 7.97 (3H, d, J-Ί, Ί, arom.); 8.21 (1H, d, J = 8.1, arom.); 10.66 (1H, s, NH); 14.30 (1H, e.g. s, COOH).
Elementāranalīze: Aprēķināts, %: C 62,46; H 4,14; N 11,50. C19H15N3O5. Atrasts,%: C 62,70; H 4,31; N 11,44.Elemental Analysis: Calculated,%: C, 62.46; H, 4.14; N, 11.50. C19H15N3O5. Found,%: C, 62.70; H, 4.31; N, 11.44.
2. piemērs: savienojums 6b sintezēts pēc vispārīgas procedūras 1:Example 2: Compound 6b was synthesized following the general procedure 1:
Iznākums 71% ( pārkristalizēts no etanola); k.p. > 270°C.Yield 71% (recrystallized from ethanol); p.p. > 270 ° C.
H-KMR (300 MHz, DMSOd6), δ, ppm: 2,51-2,80 (4H, m, 2CH2); 7,37 (1H, t, 7=7,5, arom.); 7,51 (1H, t, 7=7,5, arom.); 7,71 (1H, t, 7=7,5, arom.); 7,84 (1H, d, 7=8,0, arom.); 7,93-7,98 (2H, m, arom.); 8,18-8,22 (2H, m, arom.); 10,86 (1H, s, NH); 14,20 (1H, pl. s, COOH).1 H-NMR (300 MHz, DMSO d 6 ), δ, ppm: 2.51-2.80 (4H, m, 2CH 2 ); 7.37 (1H, t, J = 7.5, arom.); 7.51 (1H, t, J = 7.5, arom.); 7.71 (1H, t, J = 7.5, arom.); 7.84 (1H, d, J = 8.0, arom.); 7.93-7.98 (2H, m, arom.); 8.18-8.22 (2 H, m, arom.); 10.86 (1H, s, NH); 14.20 (1H, e.g. s, COOH).
Elementāranalīze: Aprēķināts, %: C 51,37; H 3,18; N 9,46. Ci9Hi4BrN3O5. Atrasts,%: C 51,35; H 3,13; N 9,35.Elemental Analysis: Calculated,%: C, 51.37; H, 3.18; N, 9.46. Ci9Hi4BrN 3 O 5th Found,%: C, 51.35; H, 3.13; N, 9.35.
3. piemērs: savienojums 6c sintezēts pēc vispārīgas procedūras 1:Example 3: Compound 6c was synthesized following the general procedure 1:
Iznākums 81% (pārkristalizēts no etanola/ ūdens, 2:1); k.p. 181-182°C.Yield 81% (recrystallized from ethanol / water 2: 1); p.p. 181-182 ° C.
H-KMR (300 MHz, DMSOd6), δ, ppm: 2,59-2,75 (4H, m, 2CH2); 6,97-7,05 (2H, m, arom.); 7,38 (1H, t, 7=7,7, arom.); 7,48 (1H, t, 7=7,4, arom.); 7,74 (1H, t, 7=7,5, arom.); 7,96 (2H, d, 7=7,9, arom.); 8,24-8,26 (1H, m, arom.); 10,35 (1H, s, NH); 11,64 (1H, s, OH); 14,78 (1H, pl. s, COOH)1 H-NMR (300 MHz, DMSO d 6 ), δ, ppm: 2.59-2.75 (4H, m, 2CH 2 ); 6.97-7.05 (2 H, m, arom.); 7.38 (1H, t, J = 7.7, arom.); 7.48 (1H, t, 7 = 7.4, arom.); 7.74 (1H, t, J = 7.5, arom.); 7.96 (2H, d, J = 7.9, arom.); 8.24-8.26 (1H, m, arom.); 10.35 (1H, s, NH); 11.64 (1H, s, OH); 14.78 (1H, e.g. s, COOH)
Elementāranalīze: Aprēķināts, %: C 58,46; H 4,13; N10,76. Ci9HisN3O6‘0,5 H2O. Atrasts,%: C 58,68; H 4,30; N 10,46.Elemental Analysis: Calculated,%: C, 58.46; H, 4.13; N10.76. C 19 H 15 N 3 O 6 · 0.5 H 2 O. Found,%: C, 58.68; H, 4.30; N, 10.46.
4. piemērs: savienojums 6d sintezēts pēc vispārīgas procedūras 1:Example 4: Compound 6d was synthesized following the general procedure 1:
Iznākums 75% ( pārkristalizēts no etanola/ ūdens, 1:1); k.p. > 270°C.Yield 75% (recrystallized from ethanol / water, 1: 1); p.p. > 270 ° C.
H-KMR (300 MHz, DMSOd6), δ, ppm: 2,49-2,76 (4H, m, 2CH2); 7,38 (1H, t, /=7,5, arom.); 7,56-7,60 (2H, pl. m, arom.); 7,12 (1H, t, /=7,5, arom.); 7,96 (1H, d, /=7,7, arom.); 8,21 (1H, d, /=8,3, arom.); 8,32 (1H, d, /=7,9, arom.); 9,10 (1H, s, arom.); 10,94 (1H, s, NH); 14,00 (1H, s, COOH).1 H-NMR (300 MHz, DMSO d 6 ), δ, ppm: 2.49-2.76 (4H, m, 2CH 2 ); 7.38 (1H, t, / = 7.5, arom.); 7.56-7.60 (2H, m, arom.); 7.12 (1H, t, = 7.5, arom.); 7.96 (1H, d, J = 7.7, arom.); 8.21 (1H, d, J = 8.3, arom.); 8.32 (1H, d, J = 7.9, arom.); 9.10 (1H, s, arom.); 10.94 (1H, s, NH); 14.00 (1H, s, COOH).
Elementāranalīze: Aprēķināts, %: C 57,60; H 4,03; N14,96. CisH^^Os-O/ H2O. Atrasts,%: C 57,65; H 4,00; N 15,04.Elemental Analysis: Calculated,%: C, 57.60; H, 4.03; N14.96. C 15 H 16 O 3 O-O / H 2 O. Found,%: C 57.65; H, 4.00; N, 15.04.
5. piemērs: savienojums 6e sintezēts pēc vispārīgas procedūras 1:Example 5: Compound 6e was synthesized following the general procedure 1:
Iznākums 69% ( pārkristalizēts no etanola); k.p.> 270°C.Yield 69% (recrystallized from ethanol); mp> 270 ° C.
H-KMR (300 MHz, DMSOd6), δ, ppm: 2,52-2,72 (4H, m, 2CH2); 7,38 (1H, t, /=7,5, arom.); 7,72 (1H, t, /=7,7, arom.); 7,85-7,89 (2H, m, arom.); 7,92 (1H, d, /=7,7, arom.); 8,20 (1H, d, /=8,1, arom.); 8.79-8,81 (2H, m, arom.); 11,04 (1H, s, NH); 14,03 (1H, pl. s, COOH).1 H-NMR (300 MHz, DMSO d 6 ), δ, ppm: 2.52-2.72 (4H, m, 2CH 2 ); 7.38 (1H, t, / = 7.5, arom.); 7.72 (1H, t, J = 7.7, arom.); 7.85-7.89 (2H, m, arom.); 7.92 (1H, d, J = 7.7, arom.); 8.20 (1H, d, J = 8.1, arom.); 8.79-8.81 (2H, m, arom.); 11.04 (1H, s, NH); 14.03 (1H, e.g. s, COOH).
Elementāranalīze: Aprēķināts, %: C 59,02; H 3,85; N15,29. C18H14N4O5.. Atrasts,%: C 58,97; H 3,82; N 14,91.Elemental Analysis: Calculated,%: C, 59.02; H, 3.85; N15.29. C 18 H 14 N 4 O 5. Found,%: C, 58.97; H, 3.82; N, 14.91.
6. piemērs: savienojums 7a sintezēts pēc vispārīgas procedūras 2:Example 6: Compound 7a was synthesized following the general procedure 2:
Iznākums 79% ( pārkristalizēts no etanola/ ūdens, 1:4); k.p. 137-140°C.Yield 79% (recrystallized from ethanol / water, 1: 4); p.p. 137-140 ° C.
H-KMR (300 MHz, DMSOd6), δ, ppm: 1,57 (3H, s, CH3); 2,19-2,78 (4H, m, 2CH2); 7,38 (1H, t, /=6,8, arom.); 7,54-7,62 (2H, m, arom.); 7,68-7,81 (2H, d, /=7,7, arom.); 7,96 (3H, pl. s, arom.); 8,07-8,18 (1H, m, arom.); 10,78 (1H, s, NH).1 H-NMR (300 MHz, DMSO d 6 ), δ, ppm: 1.57 (3H, s, CH 3 ); 2.19-2.78 (4H, m, 2CH 2 ); 7.38 (1H, t, 6.8, arom.); 7.54-7.62 (2H, m, arom.); 7.68-7.81 (2H, d, J = 7.7, arom.); 7.96 (3H, s, arom.); 8.07-8.18 (1H, m, arom.); 10.78 (1H, s, NH).
Elementāranalīze: Aprēķināts, %: C 66,27; H 5,27; N12,20. C19H17N3O3 O,5 H2O. Atrasts,%: C 66,34; H 5,08; N 12,21.Elemental Analysis: Calculated,%: C, 66.27; H, 5.27; N12.20. C 19 H 17 N 3 O 3 O, 5H 2 O. Found,%: C, 66.34; H, 5.08; N, 12.21.
7. piemērs: savienojums 7b sintezēts pēc vispārīgas procedūras 2.Example 7: Compound 7b was synthesized following the general procedure 2.
Iznākums 74% ( pārkristalizēts no etanola/ ūdens, 1:3); k.p. 148-150°C.Yield: 74% (recrystallized from ethanol / water, 1: 3); p.p. 148-150 ° C.
H-KMR (300 MHz, DMSOd6), δ, ppm: 1,56 (3H, s, CH3); 2,14-2,72 (4H, m, 2CH2); 7,38 (1H, t, /=7,5, arom.); 7,55 (1H, t, /=7,9, arom.); 7,62-7,74 (1H, m, arom.); 7,86 (1H, d, /=7,9, arom.); 7,92-7,99 (2H, m, arom.); 8,08-8,18 (2H, m, arom.); 10,83 (1H, s,NH).1 H-NMR (300 MHz, DMSO d 6 ), δ, ppm: 1.56 (3H, s, CH 3 ); 2.14 to 2.72 (4H, m, 2CH 2); 7.38 (1H, t, / = 7.5, arom.); 7.55 (1H, t, J = 7.9, arom.); 7.62-7.74 (1H, m, arom.); 7.86 (1H, d, J = 7.9, arom.); 7.92-7.99 (2H, m, arom.); 8.08-8.18 (2 H, m, arom.); 10.83 (1H, s, NH).
Elementāranalīze: Aprēķināts, %: C 53,92; H 4,05; N9,93. Ci9Hi6BrN3O3 -0,5 H2O. Atrasts,%: C 54,21; H 3,92; N 9,87.Elemental Analysis: Calculated,%: C, 53.92; H, 4.05; N, 9.93. C 19 H 16 BrN 3 O 3 • 0.5 H 2 O. Found,%: C, 54.21; H, 3.92; N, 9.87.
8. piemērs: savienojums 7c sintezēts pēc vispārīgas procedūras 2:Example 8: Compound 7c was synthesized following the general procedure 2:
Iznākums 75% ( pārkristalizēts no etanola/ ūdens, 1:1); k.p.l55-156°C.Yield 75% (recrystallized from ethanol / water, 1: 1); mp 155-156 ° C.
H-KMR (300 MHz, DMSOd6), δ, ppm: 1,55 (3H, s, CH3); 2,12-2,76 (4H, m, 2CH2); 6,96-7,10 (2H, m, arom.); 7,38 (1H, t, /=7,5, arom.); 7,49 (1H, t, /=7,2, arom.); 7,72 (1H, t, /=7,5, arom.); 7,89 (1H, d, /=8,1, arom.); 7,98 (1H, d, /=7,7, arom.); 8,098,15 (1H, m, arom.); 10,70 (1H, s, NH); 11,49 (1H, s, OH).1 H-NMR (300 MHz, DMSO d 6 ), δ, ppm: 1.55 (3H, s, CH 3 ); 2.12 to 2.76 (4H, m, 2CH 2); 6.96-7.10 (2H, m, arom.); 7.38 (1H, t, / = 7.5, arom.); 7.49 (1H, t, J = 7.2, arom.); 7.72 (1H, t, / = 7.5, arom.); 7.89 (1H, d, J = 8.1, arom.); 7.98 (1H, d, J = 7.7, arom.); 8,098.15 (1H, m, arom.); 10.70 (1H, s, NH); 11.49 (1H, s, OH).
Elementāranalīze: Aprēķināts, %: C 63,33; H 5,03; N 11,66. C19H17N3O4 -0,5 H2O. Atrasts,%: C 63,03; H 4,82; N 11,65.Elemental Analysis: Calculated,%: C, 63.33; H, 5.03; N, 11.66. C 19 H 17 N 3 O 4 • 0.5 H 2 O. Found,%: C 63.03; H, 4.82; N, 11.65.
9. piemērs: savienojums 7d sintezēts pēc vispārīgas procedūras 2:Example 9: Compound 7d was synthesized following the general procedure 2:
Iznākums 85% ( hromatogrāfiski viendabīgs bez pārkristalizēšanas); k.p.184186°C.Yield 85% (homogeneous by chromatography without recrystallization); mp 184186 ° C.
H-KMR (300 MHz, DMSOd6), δ, ppm: 1,57 (3H, s, CH3); 2,24-2,77 (4H, m, 2CH2); 7,38 (1H, t, /=7,5, arom.); 7,58-7,64 (1H, m, arom.); 7,72-7,78 (1H, m, arom.); 7,94-8,02 (1H, m, arom.); 8,04-8,20 (1H, m, arom.); 8,26-8,38 (1H, m, arom.); 8,798,81 (1H, m, arom.); 9,12 (1H, s, arom.); 10,91 (1H, s, NH).1 H-NMR (300 MHz, DMSO d 6 ), δ, ppm: 1.57 (3H, s, CH 3 ); 2.24-2.77 (4H, m, 2CH 2 ); 7.38 (1H, t, / = 7.5, arom.); 7.58-7.64 (1H, m, arom.); 7.72-7.78 (1H, m, arom.); 7.94-8.02 (1H, m, arom.); 8.04-8.20 (1H, m, arom.); 8.26-8.38 (1H, m, arom.); 8,798.81 (1H, m, arom.); 9.12 (1H, s, arom.); 10.91 (1H, s, NH).
Elementāranalīze: Aprēķināts, %: C 64,28; H 4,79; N 16,66. CisHi6N4O3. Atrasts,%: C 64,56; H 5,02; N 16,79.Elemental Analysis: Calculated,%: C, 64.28; H, 4.79; N, 16.66. CisHi6N4O third Found,%: C, 64.56; H, 5.02; N, 16.79.
10. piemērs: savienojums 7e sintezēts pēc vispārīgas procedūras 2:Example 10: Compound 7e was synthesized following the general procedure 2:
Iznākums 75% ( pārkristalizēts no etanola); k.p.230-231°C.Yield 75% (recrystallized from ethanol); mp.230-231 ° C.
H-KMR (300 MHz, DMSOd6), δ, ppm: ι,57 (3H, s, CH3); 2,24-2,74 (4H, m, 2CH2); 7,38 (1H, t, /=7,5, arom.); 7,72 (1H, t, /=7,3, arom.); 7,86 (2H, s, arom.); 7,97 (1Η, d, «7=7,3, arom.); 8,07-8,32 (1H, m, aram.); 8,84 (2H, d, «7=5,3, arom.); 11,02 (1H, s, NH).1 H-NMR (300 MHz, DMSO d 6 ), δ, ppm: ι, 57 (3H, s, CH 3 ); 2.24 to 2.74 (4H, m, 2CH 2); 7.38 (1H, t, / = 7.5, arom.); 7.72 (1H, t, J = 7.3, arom.); 7.86 (2H, s, arom.); 7.97 (1Η, d, 77 = 7.3, arom.); 8.07-8.32 (1H, m, aram.); 8.84 (2H, d, J = 5.3, arom.); 11.02 (1H, s, NH).
Elementāranalīze: Aprēķināts, %: C 64,28; H 4,79; N 16,66. C18H16N4O3 Atrasts,%: C 64,23; H 4,64; N 16,78.Elemental Analysis: Calculated,%: C, 64.28; H, 4.79; N, 16.66. C 18 H 16 N 4 O 3 Found,%: C 64.23; H, 4.64; N, 16.78.
Izmantotā literatūraLiterature used
1. Mhase S.,B.Argade N.,P. Tetrahedron, 2006, vol.62, N 42, p.9787-9826.1. Mhase S., B.Argade N., P. Tetrahedron, 2006, vol.62, N 42, pp.9787-9826.
2. Dumitrascu, F., Georgescu, E., Caira, M. R., Georgescu, F., Popa, M., Draghici, B., Dumitrescu, D. G.. Synlett, 2009, N 20, p. 3336-3341.2. Dumitrascu, F., Georgescu, E., Caira, M. R., Georgescu, F., Popa, M., Draghici, B., Dumitrescu, D. G. .. Synlett, 2009, N 20, p. 3336-3341.
3. Gackenheimer, S. L., Schaus, J. M., Gehlert, D. R.. J. Pharmacol. £xp. Ther., 1995, vol. 732, p. 113-120.3. Gackenheimer, S. L., Schaus, J. M., and Gehlert, D. R. J. Pharmacol. £ xp. Ther., 1995, vol. 732, p. 113-120.
4. Wolf, E., Dufiy, B. US Pat. 3883524, 1975; C.A. 1975, 83,131624.4. Wolf, E., Dufiy, B. US Pat. 3883524, 1975; C.A. 1975, 83, 131624.
5. Eldin, Α. M. S. Heteroatom Chem., 2003, vol. 14, N 7, p. 612-616.5. Eldin, Α. M. S. Heteroatom Chem., 2003, vol. 14, N 7, p. 612-616.
6. Iminov, R. T., Tverdokhlebov, Α. V., Tolmachev, Α. A., Volovenko, Y. M., Kostyuk, Α. N., Chemega, Α. N., Rusanov, Ε. B. Heterocycles, 2008, vol. 75, N 7, p. 1673-1680.6. Iminov, R. T., Tverdokhlebov, Α. V., Tolmachev, Α. A., Volovenko, Y. M., Kostyuk, Α. N., Chemega, Α. N., Rusanov, Ε. B. Heterocycles, 2008, vol. 75, N 7, p. 1673-1680.
7. Τημοχηη, Ε. B., BapaHCKHii, Β. A., EjiHceeBa, Γ. Ycn. xum., 1999, tom 68, βηπ., N° 1, c. 80-91.7. Τημοχηη, Ε. B., BapaHCKHii, Β. A., EjiHceeBa, Γ. Ycn. xum., 1999, tom 68, βηπ., N ° 1, c. 80-91.
8. ΙΠβΜπγκ, JI. A., HepHtK, Β. Π., Kpbicbkhb, O. C. )KopX, 2006, tom 42, βηπ. 5, c. 768-771.8. ΙΠβΜπγκ, JI. A., HepHtK, Β. Π., Kpbicbkhb, O. C.) KopX, 2006, tom 42, βηπ. 5, c. 768-771.
9. Yxhh, JI. K)., Ky3BMHHa, JI. Γ., TpHŪaHOBa, T. H., EejioycoBa, JI. B., OpnoBa, 7K. Η.. H3b. Aicau. HayK. Cep. xhm., 2008, N« 11, c. 2294-2302.9. Yxhh, JI. K)., Ky3BMHHa, JI. Γ., TpHŪaHOBa, T. H., EejioycoBa, JI. B., OpnoBa, 7K. Η .. H3b. Aicau. HayK. Cep. xhm., 2008, N «11, c. 2294-2302.
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