Синтез нових піримідо[4,5-e]індолізин- та піримідо[5,4-c]хінолізин-6-карбонових кислот
An effective method for the synthesis of previously undescribed 1,3,4,5,6a,7,8,9-octahydropyrimido[4,5-e]indolizine- and 1,3,4,5,7,8,9,10-octahydro-2H-pyrimido[5,4-c]quinolizine-6-carboxylic acids by hydrolysis and decarboxylation of new spiro-substituted derivatives was proposed. The corresponding...
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V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the National Academy of Sciences of Ukraine
2022
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Ukrainica Bioorganica Acta| _version_ | 1871193569580023808 |
|---|---|
| author | Muzychka, Luibov V. Muzychka, Oksana V. Zinchenko, Anna M. Smolii, Oleg B. |
| author_facet | Muzychka, Luibov V. Muzychka, Oksana V. Zinchenko, Anna M. Smolii, Oleg B. |
| author_institution_txt_mv | [
{
"author": "Luibov V. Muzychka",
"institution": "V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the NAS of Ukraine, Kyiv, Ukraine"
},
{
"author": "Oksana V. Muzychka",
"institution": "V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the NAS of Ukraine, Kyiv, Ukraine"
},
{
"author": "Anna M. Zinchenko",
"institution": "V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the NAS of Ukraine, Kyiv, Ukraine"
},
{
"author": "Oleg B. Smolii",
"institution": "V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the NAS of Ukraine, Kyiv, Ukraine"
}
] |
| author_sort | Muzychka, Luibov V. |
| baseUrl_str | https://bioorganica.com.ua/index.php/journal/oai |
| collection | OJS |
| datestamp_date | 2026-07-19T14:56:53Z |
| description | An effective method for the synthesis of previously undescribed 1,3,4,5,6a,7,8,9-octahydropyrimido[4,5-e]indolizine- and 1,3,4,5,7,8,9,10-octahydro-2H-pyrimido[5,4-c]quinolizine-6-carboxylic acids by hydrolysis and decarboxylation of new spiro-substituted derivatives was proposed. The corresponding spirocyclic derivatives were obtained by boiling of 6-dialkylamino-1,3-dimethyl-5-formyluracils with Meldrum's acid in acetonitrile. The reaction proceeds according to the tert-amino effect mechanism without the release of Knoevenagel condensation products. |
| doi_str_mv | 10.15407/bioorganica2022.02.036 |
| first_indexed | 2025-07-17T12:19:36Z |
| format | Article |
| fulltext |
ISSN 1814-9758. Ukr. Bioorg. Acta, 2022, Vol. 17, N 2
UDC 547.859
DOI: DOI: hpps://doi.org/10.15407/bioorganica2022.02.036
36
Ukrainica Bioorganica Acta
w w w.b io or gani c a.o rg .ua
SHORT COMMUNICATION
Synthesis of novel pyrimido[4,5-e]indolizine- and
pyrimido[5,4-c]-quinolizine-6-carboxylic acids
Liubov V. Muzychka*, Oksana V. Muzychka, Anna M. Zinchenko, Oleg B. Smolii
V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the NAS of Ukraine, Kyiv, Ukraine
Abstract: An effective method for the synthesis of previously undescribed 1,3,4,5,6a,7,8,9-octahydropyrimido[4,5-e]indolizine- and
1,3,4,5,7,8,9,10-octahydro-2H-pyrimido[5,4-c]quinolizine-6-carboxylic acids by hydrolysis and decarboxylation of new spiro-substituted
derivatives was proposed. The corresponding spirocyclic derivatives were obtained by boiling of 6-dialkylamino-1,3-dimethyl-5-
formyluracils with Meldrum's acid in acetonitrile. The reaction proceeds according to the tert-amino effect mechanism without the release
of Knoevenagel condensation products.
Keywords: 1,3-dimethyl-5-formyluracil; Meldrum’s acid; pyrimido[5,4-c]quinolizine; pyrimido[4,5-e]indolizine; tert-amino effect.
Introduction
The development of effective methods for the synthesis
of potential biologically active compounds remains one of
the essential tasks in organic chemistry. In this context,
special attention is devoted to the nitrogen-containing
heterocyclic systems that occur in nature, in particular
alkaloids. In recent decades, interest in indolizidine and
quinolizidine alkaloids containing completely hydrogenated
heterocyclic rings has been only increasing [1-3].
Tashiromine is one of the structurally simpler indolizidine
alkaloids, which was isolated from the Asian deciduous
shrub Maackia tashiroi [4-6]. This indolizidine alkaloid is
structurally related to the toxic and teratogenic
quinolizidine alkaloids, such as Lupinine, which are
contained in grain legumes of the genus Lupinus [1, 7, 8].
Lupininic acid also belongs to the compounds known as
lupinine-type alkaloids or lupin alkaloids [9]. The presence
of octahydro-2H-quinolizine and octahydroindolizine
structural units in natural alkaloids has caused significant
Received:
Revised:
Accepted:
Published online:
07.09.2022
20.09.2022
09.11.2022
30.12.2022
Corresponding author. Tel.: +380-44-573-2596;
e-mail: liubovmuzychka@gmail.com (L.V. Muzychka)
ORCID: 0000-0001-5220-6965
interest in the synthetic chemistry and modification of the
heterocyclic backbone of these compounds.
In this regard, the design and synthesis of heterocyclic
compounds containing pharmacophores of different
heterocyclic nature are promising. Taking into account the
high synthetic and biological potential of pyrimidine
derivatives the study aimed at the synthesis of new tricyclic
derivatives 1 which are structural analogs of Lupininic acid
(Figure 1).
N
N
O
O N
OH
O
N
OH
O
OH
N
( )n
1 (n = 0, 1)
Tashiromine (n = 1)
Lupinine (n = 2) Lupininic acid
( )n
Figure 1. Structures of some indolizidine and quinolizidine
alkaloids and tricyclic structural analogues 1.
In this article we report an efficient approach for the
synthesis of novel 1,3,4,5,6a,7,8,9-octahydropyrimido[4,5-
e]indolizine and 1,3,4,5,7,8,9,10-octahydro-2H-pyrimi-
do[5,4-c]quinolizine derivatives bearing carboxyl groups in
the heterocyclic system. The proposed method is based on
the preparation of spirocyclic compounds from
© Muzychka L.V. et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted
use, distribution, and reproduction in any medium, provided the original author and source are credited.
https://orcid.org/0000-0001-5220-6965
L.V. Muzychka, O.V. Muzychka et al.
37
Knoevenagel condensation products via the tert-amino
effect mechanism.
Results and Discussion
The synthesis of new spiro-substituted annulated 1,3-di-
methyluracils 4 was carried out according to Scheme 1
based on the tert-amino effect. Available 6-dialkylamino-
1,3-dimethyl-5-formyluracils 2а-с were used as starting
materials [10]. Boiling of 6-amino-substituted 5-formyl-
pyrimidines 2a-c with Meldrum's acid in acetonitrile leads
to the formation of spiro-substituted derivatives 4a,b
isolated in good yields. The structure of the compounds was
confirmed by spectroscopic methods and elemental
analysis. The characteristic signals from the CH2 group in
the 1H NMR spectrum was observed as two doublets at
2.79-2.83 ppm and 2.99-3.19 ppm, while the Н-6a proton in
spectra of compounds 4a, b were found at 2.68-3.87 ppm as
doublet. In the 13C NMR spectrum the C-6 atom resonance
appeared at 50.7-52.4 ppm, while the chiral carbon atom
was observed at 64.3-66.6 ppm.
In the case of 1,3-dimethyl-6-morpholin-4-yl-pyrimi-
dine-5-carbaldehyde (2c), the Knoevenagel condensation
product 3c was isolated even after the prolonged boiling
with Meldrum's acid.
It should be noted that several examples of the synthesis
of compound 4 analogs obtained from 6-dialkylamino-1,3-
dimethyl-5-formyluracils applying the tert-amino effect
have been reported in the literature [10-12]. The presence of
the 2,2-dimethyl-1,3-dioxane-4,6-dione fragment in the
compounds facilitates the further transformations into
carboxylic acids [13] and preparation of new functionalized
heterocyclic systems [14, 15]. Spiro-substituted derivatives
4a,b were converted into dicarboxylic acids via hydrolysis
under acidic conditions (Scheme 2). 1,3,4,5,6a,7,8,9-
Octahydropyrimido[4,5-e]indolizine-6,6-dicarboxylic acid
5a and 1,3,4,5,7,8,9,10-octahydro-2H-pyrimido[5,4-
c]quinolizine-6,6-dicarboxylic acid 5b were synthesized in
high yields by boiling tricyclic spiro derivatives 4a,b in
concentrated hydrochloric acid. The study of
decarboxylation of compounds 5a,b showed that the
reaction proceeds successfully with short-term heating of
dicarboxylic acids at 190-200 ºС in the absence of solvent
and leads to the formation of a mixture of two
diastereomers. One of the diastereoisomers of
1,3,4,5,6,6a,7,8,9,10-decahydro-2H-pyrimido[5,4-c]quinoli-
zine-6-dicarboxylic acid 1b was isolated in a spectrally pure
form using crystallization. The structure of the synthesized
compounds was confirmed by elemental analysis, 1H NMR,
13C NMR and MS spectral data.
Conclusions
In summary, several novel spirocyclic 1,3,4,5,6a,7,8,9-
octahydropyrimido[4,5-e]indolizine- and 1,3,4,5,7,8,9,10-
octahydro-2H-pyrimido[5,4-c]quinolizine derivatives were
obtained using the tert-amino effect by boiling of 6-dialkyl-
amino-1,3-dimethyl-5-formyluracils with Meldrum's acid.
An effective method for the synthesis of previ-
ously undescribed 1,3,4,5,6a,7,8,9-octahydropyrimido[4,5-
N
N
O
O
NO
N
N
O
O N
X
O
O
O
O
O
O
N
N
O
O
X
N
O
O
2a-c
MeCN,
reflux, 7-15 h
4a,b
X = - (a), CH2 (b), O (c)
3a-c
reflux
MeCN
X
O O
OO
Scheme 1. Synthesis of spiro-substituted pyrimido[4,5-e]indolizine and 2H-pyrimido[5,4-c]quinolizine derivatives 4.
O
O
N
N
O
O
X
N
O
O
OH
OH
N
N
O
O
X
N
O
O
N
N
O
O
X
N
OH
O
190-200 oC
10-15 min
4a,b
conc. HCl
reflux,
20-30 min
5a,b 1a,b
X = - (a), CH2 (b), O (c)
Scheme 2. Hydrolysis and decarboxylation of spiro-substituted pyrimido[4,5-e]-indolizine and 2H-pyrimido[5,4-c]quinolizine
derivatives 4.
ISSN 1814-9758. Ukr. Bioorg. Acta, 2022, Vol. 17, N 2
38
e]indolizine- and 1,3,4,5,7,8,9,10-octahydro-2H-
pyrimido[5,4-c]quinolizine-6-carboxylic acids was
proposed. Such a simple procedure for the synthesis of
functionalized pyrimido[4,5-e]indolizine and pyrimido[5,4-
c]quinolizine from commonly available reagents makes this
method useful for the development of bioactive compounds.
Experimental section
1Н and 13С NMR spectra were recorded on Varian
Mercury 400 (400 and 100 MHz for 1Н and 13С
respectively) and Bruker Avance DRX500 (500 and 125
MHz for 1Н and 13С respectively). Chemical shifts are
reported in ppm downfield from TMS (1H, 13C) as an
internal standard. Chromato-mass spectroscopy were
performed on an Agilent 1100 Series HPLC equipped with
diode array and Agilent LC/MSD SL mass selective
detector, ionization method – chemical ionization at
atmospheric pressure. Elemental analysis was performed at
the Analytical laboratory of the V.P. Kukhar Institute of
Bioorganic Chemistry and Petrochemistry of the NAS of
Ukraine. Melting points were determined on a Boetius hot
stage apparatus. The reaction progress and purity of the
obtained compounds were controlled by TLC on Silufol
UV-254 plates using a 19:1 mixture of CHCl3–MeOH as
eluent.
6-Dialkylamino-1,3-dimethyl-5-formyluracils 2 a-c were
synthesized as previously described [10].
General procedure for the synthesis of spiro-substituted
pyrimido[4,5-e]indolizine and 2H-pyrimido[5,4-
c]quinolizine derivatives (3, 4).
A mixture of 5 mmol appropriate 6-dialkylamino-1,3-
dimethyl-5-formyluracils 2a-c and Meldrum's acid (0.72 g,
5 mmol) in 30 mL of MeCN was refluxed for 7-15 h. The
solvent was evaporated and 10 ml of ethanol was added to
the residue. The resulted precipitate was filtered and
recrystallized from propan-2-ol.
5-[(2,2-Dimethyl-4,6-dioxo-3-dioxan-5-ylidene)methyl]-
1,3-dimethyl-6-morpholin-4-ylpyrimidine-2,4(1H,3H)-dione
(3c).
Yield 65%; mp 184-186 ºС. 1H NMR (400 MHz,
DMSO-d6) 7.90 (s, 1H, CH), 3.84-3.92 (m, 4H, 2CH2),
3.43 (s, 3H, CH3), 3.36-3.39 (m, 4H, 2CH2), 3.33 (s, 3H,
CH3), 1.76 (s, 6H, 2CH3);
13C NMR (125 MHz, DMSO-d6)
163.3 (C), 161.0 (C), 160.7 (C), 158.8 (C), 152.0 (C),
147.4 (CH), 113.9 (С), 104.5 (C), 98.2 (C), 67.1 (2CH2),
51.9 (2CH2), 36.3 (CH3), 28.7 (CH3), 27.3 (CH3), 27.2
(CH3). LC/MS (APCI) m/z 380.2 [M+H]+. Anal. calcd. for
C17H21N3O7: C, 53.82; H, 5.58; N, 11.08. Found: C, 53.45;
H, 5.70; N, 11.21.
1',2,2,3'-Tetramethyl-1',5',6a',7',8',9'-hexahydro-2'H-
spiro[1,3-dioxane-5,6'-pyrimido[4,5-e]indolizine]-
2',4,4',6(3'H)-tetrone (4a).
Yield 41%; mp 168-169 ºС. 1H NMR (400 MHz,
DMSO-d6) 3.87 (d, J 8.5 Hz, 1H, H-6a), 3.71-3.76 (m,
1H), 3.35 (s, 3H, CH3), 3.24-3.29 (m, 1H), 3.18 (s, 3H,
CH3), 2.99 (d, J 16.4 Hz, 1H) and 2.79 (d, J 16.4 Hz, 1H,
CH2), 2.24-2.35 (m, 1H), 1.90-1.96 (m, 2H), 1.76 (s, 3H,
CH3), 1.75 (s, 3H, CH3), 1.61-1.69 (m, 1H); 13C NMR (125
MHz, DMSO-d6) 169.1 (C), 166.4 (C), 161.1 (C), 151.8
(C), 150.4 (C), 105.6 (C), 86.4 (С), 66.6 (CH), 52.4 (C),
45.7 (CH2), 35.0 (CH3), 29.4 (CH3), 29.3 (CH2), 27.3 (CH2),
27.3 (CH3), 26.9 (CH3), 22.5 (CH2). LC/MS (APCI) m/z
364.1 [M+H]+. Anal. calcd. for C17H21N3O6: C, 56.19; H,
5.83; N, 11.56. Found: C, 56.27; H, 5.97; N, 11.39.
1',2,2,3'-Tetramethyl-1',5',7',8',9',10'-hexahydro-2',6a'H-
spiro[1,3-dioxane-5,6'-pyrimido[5,4-c]quinolizine]-
2',4,4',6(3'H)-tetrone (4b).
Yield 52%; mp 215-217 ºС. 1H NMR (400 MHz,
DMSO-d6) 3.68 (d, J 10.4 Hz, 1H, H-6a), 3.60 (dd, J 14.0,
1.1 Hz, 1H) and 2.98 (dd, J 11.2, 1.1 Hz, 1H, CH2), 3.31 (s,
3H, CH3), 3.19 (d, J 15.2 Hz, 1H) and 2.83 (d, J 15.2 Hz,
1H, CH2), 3.15 (s, 3H, CH3), 1.87-1.89 (m, 1H), 1.78 (s,
3H, CH3), 1.73 (s, 3H, CH3), 1.66-1.71 (m, 3H), 1.51-1.60
(m, 1H), 1.37-1.45 (m, 1H); 13C NMR (125 MHz, DMSO-
d6) 168.4 (C), 164.7 (C), 161.4 (C), 153.5 (C), 152.9 (C),
106.3 (C), 87.9 (С), 64.3 (CH), 50.7 (CH2), 50.6 (C), 36.2
(CH3), 30.3 (CH2), 29.0 (CH3), 28.4 (CH3), 27.7 (CH3), 26.6
(CH2), 24.1 (CH2), 23.2 (CH2). LC/MS (APCI) m/z 378.2
[M+H]+. Anal. calcd. for C18H23N3O6: C, 57.29; H, 6.14; N,
11.13. Found: C, 57.35; H, 5.99; N, 11.28.
General procedure for compounds 5a, b.
A mixture of 2 mmol appropriate spiro-substituted
derivatives 4a, b and 5 mL concentrated hydrochloric acid
was refluxed for 20-30 min. The resulted precipitate was
filtered, washed with water and recrystallized from ethanol.
1,3-Dimethyl-2,4-dioxo-1,3,4,5,6a,7,8,9-
octahydropyrimido[4,5-e]indolizine-6,6(2H)-dicarboxylic
acid (5a).
Yield 78%; mp 200-202 ºС. 1H NMR (400 MHz,
DMSO-d6) 3.76-3.82 (m, 1H), 3.27-3.36 (m, 2H), 2.95 (s,
3H, CH3), 2.76-2.83 (m, 2H), 2.33 (s, 3H, CH3), 2.10-2.17
(m, 1H), 1.85-2.01 (m, 2H), 1.68-1.79 (m, 1H); 13C NMR
(125 MHz, DMSO-d6) 173.9 (C), 173.0 (C), 160.7(C),
158.5 (C), 155.6 (C), 82.4 (С), 60.1 (CH), 46.7 (CH2), 46.1
(C), 34.1(CH2), 29.3 (CH2), 26.0 (CH3), 24.2 (CH3), 22.3
(CH2). LC/MS (APCI) m/z 324.1 [M+H]+. Anal. calcd. for
C14H17N3O6: C, 52.01; H, 5.30; N, 13.00. Found: C, 52.14;
H, 5.26; N, 12.89.
1,3-Dimethyl-2,4-dioxo-1,3,4,5,7,8,9,10-octahydro-2H-
pyrimido[5,4-c]quinolizine-6,6(6aH)-dicarboxylic acid
(5b).
Yield 92%; mp 188-190 ºС. 1H NMR (400 MHz,
DMSO-d6) 3.65-3.72 (m, 2H), 3.20 (s, 3H, CH3), 3.10 (s,
3H, CH3), 2.99-3.06 (m, 1H), 2.75-2.86 (m, 2H), 1.83-1.87
(m, 1H), 1.56-1.69 (m, 3H), 1.43-1.54 (m, 2H); 13C NMR
(125 MHz, DMSO-d6) 170.6 (C), 169.6 (C), 160.7(C),
153.0 (C), 152.4 (C), 88.3 (С), 60.5 (CH), 56.7 (CH2), 50.5
(C), 38.0 (CH3), 36.6(CH2), 27.6 (CH2), 27.2 (CH3), 25.4
(CH2), 23.5 (CH2). LC/MS (APCI) m/z 338.1 [M+H]+.
L.V. Muzychka, O.V. Muzychka et al.
39
Anal. calcd. for C15H19N3O6: C, 53.41; H, 5.68; N, 12.46.
Found: C, 53.35; H, 5.64; N, 12.37.
General procedure for compounds 1a, b.
2 Mmol of the corresponding dicarboxylic acid 5a, b was
heated for 10-15 min at 190-200 ºC. The reaction mixture
was cooled to ambient temperature and 10 ml of CH3CN
was added. The resulting precipitate was filtered and
recrystallized from CH3CN.
1,3-Dimethyl-2,4-dioxo-1,2,3,4,5,6,6a,7,8,9-
decahydropyrimido[4,5-e]indolizine-6-carboxylic acid (1a)
was isolated as a mixture of two diastereoisomers.
1,3-Dimethyl-2,4-dioxo-1,3,4,5,6,6a,7,8,9,10-decahydro-
2H-pyrimido[5,4-c]quinolizine-6-carboxylic acid (1b).
Yield 54%; mp 236-238 ºС. 1H NMR (400 MHz,
DMSO-d6) 12.62 (br s, 1H, OH), 3.25 (s, 3H, CH3), 3.14
(s, 3H, CH3), 2.98-3.05 (m, 2H), 2.83-2.96 (m, 1H), 2.70-
2.79 (m, 1H), 2.61 (dd, J 16.0, 6.4 Hz, 1H) and 2.37 (dd,
J 11.6, 16,0 Hz, 1H, CH2), 1.76-1.84 (m, 1H), 1.56-1.66 (m,
5H); 13C NMR (125 MHz, DMSO-d6) 175.1 (C), 162.0
(C), 153.9 (C), 152.3 (C), 89.1 (С), 58.7 (CH), 51.0 (CH2),
42.2 (CH), 37.8 (CH3), 34.7 (CH2), 27.8 (CH3), 27.0 (CH2),
25.4 (CH2), 25.2 (CH2). LC/MS (APCI) m/z 294.2 [M+H]+.
Anal. calcd. for C14H19N3O4: C, 57.33; H, 6.53; N, 14.33.
Found: C, 57.30; H, 6.54; N, 14.38.
Notes
The authors declare no conflict of interest.
References
1. Michael, J.P. Simple Indolizidine and Quinolizidine Alkaloids. The
Alkaloids: Chemistry and Biology. 2016, 75, 1-98.
2. Michael, J.P. Indolizidine and quinolizidine alkaloids. Nat. Prod.
Rep. 2008, 25, 139-165
3. Michael, J.P. Indolizidine and quinolizidine alkaloids. Nat. Prod.
Rep. 2007, 24, 191-222.
4. Zhang, J.; Morris‐Natschke, S.L.; Ma, D.; Shang, X.; Yang, C.; Liu,
Y.; Lee, K. Biologically active indolizidine alkaloids. Med. Res. Rev.
2020, 41, 928-960.
5. Cutter, A.C.; Miller, I.R.; Keily, J.F.; Bellingham, R K.; Light, M.E.;
Brown, R.C.D. Total Syntheses of (−) Epilupinine and
(−)-Tashiromine Using Imino-Aldol Reactions. Org. Lett. 2011, 13,
3988-3991.
6. Bates, R.W.; Boonsombat, J. The pyridinium reduction route to
alkaloids: a synthesis of (±)-tashiromine. J. Chem. Soc., Perkin
Trans. 1. 2001, 7, 654-656.
7. Airiau, E.; Spangenberg, T.; Girard, N.; Breit, B.; Mann, A. Short
Access to (+)-Lupinine and (+)-Epiquinamide via Double
Hydroformylation. Org. Lett. 2010, 12, 528-531.
8. Reinhard, H.; Rupp, H.; Sager, F.; Streule, M.; Zoller, O. Quino-
lizidine alkaloids and phomopsins in lupin seeds and lupin containing
food. J. Chromatogr. A. 2006, 1112, 353-360.
9. Aslanov, K.A.; Kasymov, T.K.; Sadykov, A.S; Ishbaev A.I. The
product of the condensation of lupininic acid with piperidine. Chem.
Heterocycl. Comp. 1970, 6, 454-456.
10. Baruah, B.; Bhuyan, P.J. Tertiary amine effect: synthesis of some
novel spirosubstituted pyrido[2,3-d]pyrimidines. Tetrahedron Lett.
2009, 50, 243-245.
11. Bhuyan, P.J.; Lekhok, K.C.; Sandhu, J.S. Studies on Uracils:
Synthesis of Novel Uracil Analogues via 1,5- and 1,6-Intramolecular
Cycloaddition Reactions. J. Chem. Res. 1998, 9, 502-503.
12. Wamhoff, H.; Kramer-Hoß, V. Reactions of Uracils, 22. Synthesis
of Pyrimido[5,4-c]quinolizines. Liebigs Annalen. 1997, 7, 1619-
1625.
13. Helavi, V.B.; Solabannavar, S.B.; Desai, U.V.; Mane, R.B.
Microwave assisted hydrolysis of Meldrum’s acid derivatives and
decarboxylation of derived malonic acids. J. Chem. Res. 2003, 3,
174-175.
14. Rabong, C.; Hametner, C.; Mereiter, K.; Kartsev, V.G.; Jordis, U.
Scope and Limitations of the T-Reaction Employing Some
Functionalized C-H-Acids and Naturally Occurring Secondary
Amines. Heterocycles. 2008, 75, 799-838.
15. Ryabukhin, S.V.; Plaskon, A.S.; Volochnyuk, D.M.; Pipko, S.E.;
Tolmachev, A.A. Facile One-Pot Synthesis of 1,2,3,4-
Tetrahydroquinoline-3-carboxylic Acids and Their Heterocyclic
Analogs. Synth. Commun. 2008, 38, 3032-3043.
Синтез нових піримідо[4,5-e]індолізин- та піримідо[5,4-c]хінолізин-6-карбонових
кислот
Л.В. Музичка*, О.В. Музичка, А.М. Зінченко, О.Б. Смолій
Інститут біоорганічної хімії та нафтохімії ім. В.П. Кухаря НАН України, Київ, Україна.
Резюме: Запропоновано ефективний метод синтезу раніше не описаних 1,3,4,5,6a,7,8,9-октагідропіримідо[4,5-e]індолізин- та 1,3,4,5,7,8,9,10 -
октагідро-2Н-піримідо[5,4-с]хінолізин-6-карбонових кислот шляхом гідролізу та декарбоксилювання нових спірозаміщених похідних. Відповідні
спіроциклічні похідні були отримані кип'ятінням 6-діалкіламіно-1,3-диметил-5-формілурацилів з кислотою Мелдрума в ацетонітрилі. Реакція
протікає за механізмом трет-аміно ефекту без виділення продуктів конденсації Кневенагеля.
Ключові слова: 1,3-диметил-5-формілурацил; кислота Мелдрума; піримідо[5,4-с]хіно лізин; піримідо[4,5-е]індолізин; трет-аміно ефект.
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| id | oai:ojs2.bioorganica.com.ua:article-34 |
| institution | Ukrainica Bioorganica Acta |
| keywords_txt_mv | keywords |
| language | English |
| last_indexed | 2026-07-20T01:00:48Z |
| publishDate | 2022 |
| publisher | V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the National Academy of Sciences of Ukraine |
| record_format | ojs |
| resource_txt_mv | bioorganicacomua/39/8b5b015285865be1a851f0ab7745cb39.pdf |
| spelling | oai:ojs2.bioorganica.com.ua:article-342026-07-19T14:56:53Z Synthesis of novel pyrimido[4,5-e]indolizine- and pyrimido[5,4-c]quinolizine-6-carboxylic acids Синтез нових піримідо[4,5-e]індолізин- та піримідо[5,4-c]хінолізин-6-карбонових кислот Muzychka, Luibov V. Muzychka, Oksana V. Zinchenko, Anna M. Smolii, Oleg B. 1,3-dimethyl-5-formyluracil Meldrum’s acid pyrimido[5,4-c]quinolizine pyrimido[4,5-e]indolizine tert-amino effect 1,3-диметил-5-формілурацил кислота Мелдрума піримідо[5,4-с]хіно лізин піримідо[4,5-е]індолізин трет-аміно ефект An effective method for the synthesis of previously undescribed 1,3,4,5,6a,7,8,9-octahydropyrimido[4,5-e]indolizine- and 1,3,4,5,7,8,9,10-octahydro-2H-pyrimido[5,4-c]quinolizine-6-carboxylic acids by hydrolysis and decarboxylation of new spiro-substituted derivatives was proposed. The corresponding spirocyclic derivatives were obtained by boiling of 6-dialkylamino-1,3-dimethyl-5-formyluracils with Meldrum's acid in acetonitrile. The reaction proceeds according to the tert-amino effect mechanism without the release of Knoevenagel condensation products. Запропоновано ефективний метод синтезу раніше не описаних 1,3,4,5,6a,7,8,9-октагідропіримідо[4,5-e]індолізин- та 1,3,4,5,7,8,9,10 -октагідро-2Н-піримідо[5,4-с]хінолізин-6-карбонових кислот шляхом гідролізу та декарбоксилювання нових спірозаміщених похідних. Відповідні спіроциклічні похідні були отримані кип'ятінням 6-діалкіламіно-1,3-диметил-5-формілурацилів з кислотою Мелдрума в ацетонітрилі. Реакція протікає за механізмом трет-аміно ефекту без виділення продуктів конденсації Кневенагеля. V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the National Academy of Sciences of Ukraine 2022-12-30 Article Article application/pdf https://bioorganica.com.ua/index.php/journal/article/view/34 10.15407/bioorganica2022.02.036 Ukrainica Bioorganica Acta; Vol. 17 No. 2 (2022): Ukrainica Bioorganica Acta; 36-39 Ukrainica Bioorganica Acta; Том 17 № 2 (2022): Ukrainica Bioorganica Acta; 36-39 1814-9766 1814-9758 10.15407/bioorganica2022.02 en https://bioorganica.com.ua/index.php/journal/article/view/34/52 Copyright (c) 2022 Luibov V. Muzychka, Oksana V. Muzychka, Anna M. Zinchenko, Oleg B. Smolii https://creativecommons.org/licenses/by/4.0 |
| spellingShingle | 1,3-диметил-5-формілурацил кислота Мелдрума піримідо[5,4-с]хіно лізин піримідо[4,5-е]індолізин трет-аміно ефект Muzychka, Luibov V. Muzychka, Oksana V. Zinchenko, Anna M. Smolii, Oleg B. Синтез нових піримідо[4,5-e]індолізин- та піримідо[5,4-c]хінолізин-6-карбонових кислот |
| title | Синтез нових піримідо[4,5-e]індолізин- та піримідо[5,4-c]хінолізин-6-карбонових кислот |
| title_alt | Synthesis of novel pyrimido[4,5-e]indolizine- and pyrimido[5,4-c]quinolizine-6-carboxylic acids |
| title_full | Синтез нових піримідо[4,5-e]індолізин- та піримідо[5,4-c]хінолізин-6-карбонових кислот |
| title_fullStr | Синтез нових піримідо[4,5-e]індолізин- та піримідо[5,4-c]хінолізин-6-карбонових кислот |
| title_full_unstemmed | Синтез нових піримідо[4,5-e]індолізин- та піримідо[5,4-c]хінолізин-6-карбонових кислот |
| title_short | Синтез нових піримідо[4,5-e]індолізин- та піримідо[5,4-c]хінолізин-6-карбонових кислот |
| title_sort | синтез нових піримідо[4,5-e]індолізин- та піримідо[5,4-c]хінолізин-6-карбонових кислот |
| topic | 1,3-диметил-5-формілурацил кислота Мелдрума піримідо[5,4-с]хіно лізин піримідо[4,5-е]індолізин трет-аміно ефект |
| topic_facet | 1,3-dimethyl-5-formyluracil Meldrum’s acid pyrimido[5,4-c]quinolizine pyrimido[4,5-e]indolizine tert-amino effect 1,3-диметил-5-формілурацил кислота Мелдрума піримідо[5,4-с]хіно лізин піримідо[4,5-е]індолізин трет-аміно ефект |
| url | https://bioorganica.com.ua/index.php/journal/article/view/34 |
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