TY  - JOUR
AU  - Popović-Djordjević, Jelena
AU  - Ivanović, MD
AU  - Kiricojević, Vesna D.
PY  - 2005
UR  - http://aspace.agrif.bg.ac.rs/handle/123456789/1022
AB  - The synthesis of various functionalized or spirobicyclic glutarimides by a novel tandem process has been disclosed. The reaction involves a base-catalyzed Michael addition of active methylene compounds to secondary conjugated amides, followed by intramolecular N-acylation of the carboxamido group. It provides a relatively general and simple access to useful synthetic intermediaries and potentially active pharmacological compounds. In addition, a novel group of spirobicyclic systems has been synthesized.
PB  - Pergamon-Elsevier Science Ltd, Oxford
T2  - Tetrahedron Letters
T1  - A novel tandem process leading to functionalized glutarimides
EP  - 2614
IS  - 15
SP  - 2611
VL  - 46
DO  - 10.1016/j.tetlet.2005.02.087
ER  - 

@article{
author = "Popović-Djordjević, Jelena and Ivanović, MD and Kiricojević, Vesna D.",
year = "2005",
abstract = "The synthesis of various functionalized or spirobicyclic glutarimides by a novel tandem process has been disclosed. The reaction involves a base-catalyzed Michael addition of active methylene compounds to secondary conjugated amides, followed by intramolecular N-acylation of the carboxamido group. It provides a relatively general and simple access to useful synthetic intermediaries and potentially active pharmacological compounds. In addition, a novel group of spirobicyclic systems has been synthesized.",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Tetrahedron Letters",
title = "A novel tandem process leading to functionalized glutarimides",
pages = "2614-2611",
number = "15",
volume = "46",
doi = "10.1016/j.tetlet.2005.02.087"
}

Popović-Djordjević, J., Ivanović, M.,& Kiricojević, V. D.. (2005). A novel tandem process leading to functionalized glutarimides. in Tetrahedron Letters
Pergamon-Elsevier Science Ltd, Oxford., 46(15), 2611-2614.
https://doi.org/10.1016/j.tetlet.2005.02.087

Popović-Djordjević J, Ivanović M, Kiricojević VD. A novel tandem process leading to functionalized glutarimides. in Tetrahedron Letters. 2005;46(15):2611-2614.
doi:10.1016/j.tetlet.2005.02.087 .

Popović-Djordjević, Jelena, Ivanović, MD, Kiricojević, Vesna D., "A novel tandem process leading to functionalized glutarimides" in Tetrahedron Letters, 46, no. 15 (2005):2611-2614,
https://doi.org/10.1016/j.tetlet.2005.02.087 . .

TY  - JOUR
AU  - Ivanović, Milovan D.
AU  - Mićović, I.V.
AU  - Vučković, Sonja M.
AU  - Prostran, Milica Š.
AU  - Todorović, Zoran M.
AU  - Ivanović, Evica
AU  - Kiricojević, Vesna D.
AU  - Popović-Djordjević, Jelena
AU  - Došen-Mićović, Ljiljana I.
PY  - 2004
UR  - http://aspace.agrif.bg.ac.rs/handle/123456789/833
AB  - An efficient, five-step synthetic approach to various acyclic 1,3-diamines has been developed and applied to the preparation of a novel class of open-chained fentanyl analogues. The acyclic derivatives 5.1–5.5 (all new compounds) were synthesized with the aim of estimating the significance of the piperidine ring for the opioid analgesic activity of anilido-piperidines. The starting β-keto-amide 1.1, prepared by the aminolysis of methyl acetoacetate with methylphenethylamine, (93 % yield), was successively reacted with NaH and BuLi, to form the highly reactive α,γ-dienolate anion 1.1a. Regio and chemoselective γ-alkylation of the dienolate with various primary and secondary alkyl halides furnished the β-keto-amides 1.2–1.5 (76–91 %). Reductive amination of the keto-amides 1.1–1.5 with aniline and Zn powder in acetic acid, via the enamine intermediates 2.1–2.5, afforded the β-anilino amides 3.1–3.5 (74–85 %). After reductive deoxygenation of the tertiary amide group, using in situ generated diborane, the corresponding 1,3-diamines 4.1–4.5 were obtained (87–97 %). The synthesis of (±)-2,3-seco-fentanyls 5.1–5.5 was completed by N-acylation of the diamines 4.1–4.5 with propionyl chloride, followed by precipitation of the monooxalate salts (86–95 %). The parent compound, 2,3-seco-fentanyl 5.1, was found to be a 40 times less potent narcotic analgesic than fentanyl but still 5–6 times more active than morphine in rats, while i-Pr derivative 5.3 was inactive. Apart from the pharmacological significance, the general procedure described herein may afford various functionalized, 1,3-diamines as potential complexing agents and building blocks for the synthesis of aza-crown ethers.
AB  - Razvijen je efikasan postupak za dobijanje različitih acikličnih 1,3-diamina u pet faza, i primenjen u sintezi nove klase analoga fentanila otvorenog niza. Derivati 5.1–5.5 (svi su nova jedinjenja) sintetisani su sa ciljem da se proceni uticaj piperidinskog prstena na opioidnoanalgetičku aktivnost anilido-piperidina. Polazni β-keto-amid 1.1, dobijen aminolizom metilacetoacetata metilfenetilaminom (prinos 93 %), bio je sukcesivno tretiran sa NaH i BuLi, pri čemu je postao veoma reaktivni α,γ-dienolatni anjon 1.1a. Regio- i hemoselektivnim γ-alkilovanjem ovog dienolata različitim primarnim i sekundarnim alkil-halogenidima, dobijeni su β-keto-amidi 1.2–1.5 (prinos 76–91 %). Reduktivnim aminovanjem keto-amida 1.1–1.5 pomoću Zn praha i sirćetne kiseline, preko enaminskih intermedijera 2.1–2.5, postali su -anilino-amidi 3.1–3.5 (prinos 74–85 %). Posle reduktivne deoksigenacije tercijene amidne funkcije, koristeći in situ generisani diboran, odgovarajući 1,3-diamini 4.1–4.5 izolovani su u prinosima 87–97 %. Sinteza (±)-2,3-seco-fentanila 5.1–5.5 završena je N-acilovanjem diamina 4.1–4.5 propionil-hloridom, a zatim taloženjem u obliku monooksalatnih soli (prinos 86–95 %). Nađeno je da je osnovno jedinjenje, 2,3-seco fentanil 5.1, 40 puta slabiji narkotički analgetik od fentanila, ali još uvek 5–6 puta aktivniji od morfina u pacova, dok je i-Pr derivat 5.3 bio neaktivan. Osim farmakološkog značaja, opštim postupkom prikazanim u ovom radu, mogu se sintetisati različiti 1,3-diamini, uključujući i one sa funkcionalnim grupama. Ova jedinjenja mogu biti potencijalno značajna kao kompleksirajući agensi i kao intermedijeri u sintezi aza-kraun-etara.
PB  - Srpsko hemijsko društvo, Beograd
T2  - JOURNAL OF THE SERBIAN CHEMICAL SOCIETY
T1  - The synthesis and pharmacological evaluation of (±)-2, 3- seco-fentanyl analogues
T1  - Sinteza i farmakološko ispitivanje (±)-2,3-seco-analoga fentanila
EP  - 968
IS  - 11
SP  - 955
VL  - 69
DO  - 10.2298/JSC0411955I
ER  - 

@article{
author = "Ivanović, Milovan D. and Mićović, I.V. and Vučković, Sonja M. and Prostran, Milica Š. and Todorović, Zoran M. and Ivanović, Evica and Kiricojević, Vesna D. and Popović-Djordjević, Jelena and Došen-Mićović, Ljiljana I.",
year = "2004",
abstract = "An efficient, five-step synthetic approach to various acyclic 1,3-diamines has been developed and applied to the preparation of a novel class of open-chained fentanyl analogues. The acyclic derivatives 5.1–5.5 (all new compounds) were synthesized with the aim of estimating the significance of the piperidine ring for the opioid analgesic activity of anilido-piperidines. The starting β-keto-amide 1.1, prepared by the aminolysis of methyl acetoacetate with methylphenethylamine, (93 % yield), was successively reacted with NaH and BuLi, to form the highly reactive α,γ-dienolate anion 1.1a. Regio and chemoselective γ-alkylation of the dienolate with various primary and secondary alkyl halides furnished the β-keto-amides 1.2–1.5 (76–91 %). Reductive amination of the keto-amides 1.1–1.5 with aniline and Zn powder in acetic acid, via the enamine intermediates 2.1–2.5, afforded the β-anilino amides 3.1–3.5 (74–85 %). After reductive deoxygenation of the tertiary amide group, using in situ generated diborane, the corresponding 1,3-diamines 4.1–4.5 were obtained (87–97 %). The synthesis of (±)-2,3-seco-fentanyls 5.1–5.5 was completed by N-acylation of the diamines 4.1–4.5 with propionyl chloride, followed by precipitation of the monooxalate salts (86–95 %). The parent compound, 2,3-seco-fentanyl 5.1, was found to be a 40 times less potent narcotic analgesic than fentanyl but still 5–6 times more active than morphine in rats, while i-Pr derivative 5.3 was inactive. Apart from the pharmacological significance, the general procedure described herein may afford various functionalized, 1,3-diamines as potential complexing agents and building blocks for the synthesis of aza-crown ethers., Razvijen je efikasan postupak za dobijanje različitih acikličnih 1,3-diamina u pet faza, i primenjen u sintezi nove klase analoga fentanila otvorenog niza. Derivati 5.1–5.5 (svi su nova jedinjenja) sintetisani su sa ciljem da se proceni uticaj piperidinskog prstena na opioidnoanalgetičku aktivnost anilido-piperidina. Polazni β-keto-amid 1.1, dobijen aminolizom metilacetoacetata metilfenetilaminom (prinos 93 %), bio je sukcesivno tretiran sa NaH i BuLi, pri čemu je postao veoma reaktivni α,γ-dienolatni anjon 1.1a. Regio- i hemoselektivnim γ-alkilovanjem ovog dienolata različitim primarnim i sekundarnim alkil-halogenidima, dobijeni su β-keto-amidi 1.2–1.5 (prinos 76–91 %). Reduktivnim aminovanjem keto-amida 1.1–1.5 pomoću Zn praha i sirćetne kiseline, preko enaminskih intermedijera 2.1–2.5, postali su -anilino-amidi 3.1–3.5 (prinos 74–85 %). Posle reduktivne deoksigenacije tercijene amidne funkcije, koristeći in situ generisani diboran, odgovarajući 1,3-diamini 4.1–4.5 izolovani su u prinosima 87–97 %. Sinteza (±)-2,3-seco-fentanila 5.1–5.5 završena je N-acilovanjem diamina 4.1–4.5 propionil-hloridom, a zatim taloženjem u obliku monooksalatnih soli (prinos 86–95 %). Nađeno je da je osnovno jedinjenje, 2,3-seco fentanil 5.1, 40 puta slabiji narkotički analgetik od fentanila, ali još uvek 5–6 puta aktivniji od morfina u pacova, dok je i-Pr derivat 5.3 bio neaktivan. Osim farmakološkog značaja, opštim postupkom prikazanim u ovom radu, mogu se sintetisati različiti 1,3-diamini, uključujući i one sa funkcionalnim grupama. Ova jedinjenja mogu biti potencijalno značajna kao kompleksirajući agensi i kao intermedijeri u sintezi aza-kraun-etara.",
publisher = "Srpsko hemijsko društvo, Beograd",
journal = "JOURNAL OF THE SERBIAN CHEMICAL SOCIETY",
title = "The synthesis and pharmacological evaluation of (±)-2, 3- seco-fentanyl analogues, Sinteza i farmakološko ispitivanje (±)-2,3-seco-analoga fentanila",
pages = "968-955",
number = "11",
volume = "69",
doi = "10.2298/JSC0411955I"
}

Ivanović, M. D., Mićović, I.V., Vučković, S. M., Prostran, M. Š., Todorović, Z. M., Ivanović, E., Kiricojević, V. D., Popović-Djordjević, J.,& Došen-Mićović, L. I.. (2004). The synthesis and pharmacological evaluation of (±)-2, 3- seco-fentanyl analogues. in JOURNAL OF THE SERBIAN CHEMICAL SOCIETY
Srpsko hemijsko društvo, Beograd., 69(11), 955-968.
https://doi.org/10.2298/JSC0411955I

Ivanović MD, Mićović I, Vučković SM, Prostran MŠ, Todorović ZM, Ivanović E, Kiricojević VD, Popović-Djordjević J, Došen-Mićović LI. The synthesis and pharmacological evaluation of (±)-2, 3- seco-fentanyl analogues. in JOURNAL OF THE SERBIAN CHEMICAL SOCIETY. 2004;69(11):955-968.
doi:10.2298/JSC0411955I .

Ivanović, Milovan D., Mićović, I.V., Vučković, Sonja M., Prostran, Milica Š., Todorović, Zoran M., Ivanović, Evica, Kiricojević, Vesna D., Popović-Djordjević, Jelena, Došen-Mićović, Ljiljana I., "The synthesis and pharmacological evaluation of (±)-2, 3- seco-fentanyl analogues" in JOURNAL OF THE SERBIAN CHEMICAL SOCIETY, 69, no. 11 (2004):955-968,
https://doi.org/10.2298/JSC0411955I . .

TY  - JOUR
AU  - Kiricojević, Vesna D.
AU  - Ivanović, Milovan D.
AU  - Mićović, I.V.
AU  - Popović-Djordjević, Jelena
AU  - Roglić, Goran M.
AU  - Došen-Mićović, Ljiljana I.
PY  - 2002
UR  - http://aspace.agrif.bg.ac.rs/handle/123456789/493
AB  - An efficient synthesis of methyl 4-[(1-oxopropyl)phenylamino]piperidine-4-carboxylate (7) has been developed starting from 1-benzylpiperidin-4-one (1). The compound is a key intermediate in the synthesis of new generation, highly active narcotic analgesics, such as remifintanil, as well as the novel classes of fentanyl analogues. An optimized Strecker-type condensation of piperidone 1 with aniline and HCN yielded the anilino-nitrile 2(≈90%) which, upon selective hydrolysis with conc. H2SO4, gave the anilino-amide 3.After vigorous basic hydrolysis of 3, followed by acidification and successive treatment with SOCl2 and MeOH, the anilino-ester 5 was obtained (40–45%, in 3 steps). N-Acylation of 5 with propionyl chloride yielded the anilido-ester 6(70–80%) In the final step, the catalytic N-debenzylation of 6 was examined under various conditions and optimized to yield 7 in near quantitative yields.
AB  - U ovom radu razvijena je efikasna sinteza metil 4-[(1-oksopropil)fenilamino]piperidin-4-karboksilata (7), prolazeći od 1-benzil piperidin-4-on-1 (1). Jedinjenje 7 je ključni intermedijer u sintezi nove generacije visoko aktivnih narkotičkih analgetika, kao što je remifentanil a takođe i novih klasa analoga fentanyla. U optimizovanoj Strecker-ovoj kondenzaciji priperidona 1 sa anilinom i HCN, dobijen je anilino-nitril 2 (≈90%) prinos čijom je selektivnom hidrolizom pomoću konc. H2SO4 postao anilino-amid 3. Intenzivnom baznom hidrolizom ovog intermedijera, zakišeljavanjem a zatim sukcesivno reakcijom sa SOCl2 i MeOH sintetisan je anilino-estar 5 (≈40–45% prinos u 3 faze). N-acelovanjem anilino-estra 5 sa propionil hloridom postao je anilido-estar 6 (≈70–80% prinos). U poslednjom fazi sinteze izvršena je optimizacija katalitičkog N-debenzilovanja anilido-estra 6 do finalnog proizvoda 7, u približno kvantitativnom prinosu.
PB  - Srpsko hemijsko društvo, Beograd
T2  - JOURNAL OF THE SERBIAN CHEMICAL SOCIETY
T1  - An optimized synthesis of a key pharmaceutical intermediate methyl 4-[(1-oxopropyl)phenylamino]piperidine-4-carboxylate
T1  - Optimizovana sinteza značajnog farmaceutskog intermedijera metil 4-[(1-oksopropil)fenilamino]piperidin-4-karboksilata
EP  - 802
IS  - 12
SP  - 793
VL  - 67
DO  - 10.2298/JSC0212793K
ER  - 

@article{
author = "Kiricojević, Vesna D. and Ivanović, Milovan D. and Mićović, I.V. and Popović-Djordjević, Jelena and Roglić, Goran M. and Došen-Mićović, Ljiljana I.",
year = "2002",
abstract = "An efficient synthesis of methyl 4-[(1-oxopropyl)phenylamino]piperidine-4-carboxylate (7) has been developed starting from 1-benzylpiperidin-4-one (1). The compound is a key intermediate in the synthesis of new generation, highly active narcotic analgesics, such as remifintanil, as well as the novel classes of fentanyl analogues. An optimized Strecker-type condensation of piperidone 1 with aniline and HCN yielded the anilino-nitrile 2(≈90%) which, upon selective hydrolysis with conc. H2SO4, gave the anilino-amide 3.After vigorous basic hydrolysis of 3, followed by acidification and successive treatment with SOCl2 and MeOH, the anilino-ester 5 was obtained (40–45%, in 3 steps). N-Acylation of 5 with propionyl chloride yielded the anilido-ester 6(70–80%) In the final step, the catalytic N-debenzylation of 6 was examined under various conditions and optimized to yield 7 in near quantitative yields., U ovom radu razvijena je efikasna sinteza metil 4-[(1-oksopropil)fenilamino]piperidin-4-karboksilata (7), prolazeći od 1-benzil piperidin-4-on-1 (1). Jedinjenje 7 je ključni intermedijer u sintezi nove generacije visoko aktivnih narkotičkih analgetika, kao što je remifentanil a takođe i novih klasa analoga fentanyla. U optimizovanoj Strecker-ovoj kondenzaciji priperidona 1 sa anilinom i HCN, dobijen je anilino-nitril 2 (≈90%) prinos čijom je selektivnom hidrolizom pomoću konc. H2SO4 postao anilino-amid 3. Intenzivnom baznom hidrolizom ovog intermedijera, zakišeljavanjem a zatim sukcesivno reakcijom sa SOCl2 i MeOH sintetisan je anilino-estar 5 (≈40–45% prinos u 3 faze). N-acelovanjem anilino-estra 5 sa propionil hloridom postao je anilido-estar 6 (≈70–80% prinos). U poslednjom fazi sinteze izvršena je optimizacija katalitičkog N-debenzilovanja anilido-estra 6 do finalnog proizvoda 7, u približno kvantitativnom prinosu.",
publisher = "Srpsko hemijsko društvo, Beograd",
journal = "JOURNAL OF THE SERBIAN CHEMICAL SOCIETY",
title = "An optimized synthesis of a key pharmaceutical intermediate methyl 4-[(1-oxopropyl)phenylamino]piperidine-4-carboxylate, Optimizovana sinteza značajnog farmaceutskog intermedijera metil 4-[(1-oksopropil)fenilamino]piperidin-4-karboksilata",
pages = "802-793",
number = "12",
volume = "67",
doi = "10.2298/JSC0212793K"
}

Kiricojević, V. D., Ivanović, M. D., Mićović, I.V., Popović-Djordjević, J., Roglić, G. M.,& Došen-Mićović, L. I.. (2002). An optimized synthesis of a key pharmaceutical intermediate methyl 4-[(1-oxopropyl)phenylamino]piperidine-4-carboxylate. in JOURNAL OF THE SERBIAN CHEMICAL SOCIETY
Srpsko hemijsko društvo, Beograd., 67(12), 793-802.
https://doi.org/10.2298/JSC0212793K

Kiricojević VD, Ivanović MD, Mićović I, Popović-Djordjević J, Roglić GM, Došen-Mićović LI. An optimized synthesis of a key pharmaceutical intermediate methyl 4-[(1-oxopropyl)phenylamino]piperidine-4-carboxylate. in JOURNAL OF THE SERBIAN CHEMICAL SOCIETY. 2002;67(12):793-802.
doi:10.2298/JSC0212793K .

Kiricojević, Vesna D., Ivanović, Milovan D., Mićović, I.V., Popović-Djordjević, Jelena, Roglić, Goran M., Došen-Mićović, Ljiljana I., "An optimized synthesis of a key pharmaceutical intermediate methyl 4-[(1-oxopropyl)phenylamino]piperidine-4-carboxylate" in JOURNAL OF THE SERBIAN CHEMICAL SOCIETY, 67, no. 12 (2002):793-802,
https://doi.org/10.2298/JSC0212793K . .