Microwave-assisted synthesis of acyclic c-nucleosides from 1,2- and 1,3-diketones

Article abstract of DOI:10.1080/15257770902830997

A simple, rapid and regioselective approach for the synthesis of C-acyclic nucleosides 3, 4, 6, and 9 of dihydropyrimidine, imidazole and indeno[1,2-b]pyridine-9-one derived from 1,2- and 1,3-diketones was performed. By using DMF or pyridine as solvent or

Full text of DOI:10.1080/15257770902830997

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Microwave-Assisted Synthesis of Acyclic
C-Nucleosides from 1,2- and 1,3-
Diketones
Najim A. Al-Masoudi a , Bahjat. A. Saeed b , Ali H. Essa c & Yaseen A.
Al-Soud d
a Fachbereich Chemie, Universität Konstanz, Konstanz, Germany
b Department of Chemistry, College of Education, University of
Basrah, Basrah, Iraq
c Department of Chemistry, College of Science, University of Basrah,
Basrah, Iraq
d Department of Chemistry, College of Science, University of Al al-
Bayt, Al-Mafraq, Jordan
Published online: 30 Mar 2009.
To cite this article: Najim A. Al-Masoudi , Bahjat. A. Saeed , Ali H. Essa & Yaseen A. Al-Soud (2009)
Microwave-Assisted Synthesis of Acyclic C-Nucleosides from 1,2- and 1,3-Diketones, Nucleosides,
Nucleotides and Nucleic Acids, 28:3, 175-183, DOI: 10.1080/15257770902830997
To link to this article: http://dx.doi.org/10.1080/15257770902830997
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Nucleosides, Nucleotides and Nucleic Acids, 28:175–183, 2009
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1525-7770 print / 1532-2335 online
DOI: 10.1080/15257770902830997
MICROWAVE-ASSISTED SYNTHESIS OF ACYCLIC C-NUCLEOSIDES
FROM 1,2- AND 1,3-DIKETONES
Najim A. Al-Masoudi,1 Bahjat. A. Saeed,2 Ali H. Essa,3 and Yaseen
A. Al-Soud4
1Fachbereich Chemie, Universita¨t Konstanz, Konstanz, Germany
2Department of Chemistry, College of Education, University of Basrah, Basrah, Iraq
3Department of Chemistry, College of Science, University of Basrah, Basrah, Iraq
4Department of Chemistry, College of Science, University of Al al-Bayt, Al-Mafraq, Jordan
A simple, rapid and regioselective approach for the synthesis of C-acyclic nucleosides 3, 4, 6,
2
and 9 of dihydropyrimidine, imidazole and indeno[1,2-b]pyridine-9-one derived from 1,2- and
1,3-diketones was performed. By using DMF or pyridine as solvent or bentonite clay as a support,
in the presence of TMSTf, ZnCl2, NH4OAc, or NH4NO3, all the desired products were obtained
within 5−25 minutes under microwave irradiation (MWI). Acid hydrolysis of 6 and 9 afforded the
free acyclic C-nucleosides 7 and 10, respectively. Upon treatment with NaOMe under MWI, 3 and
14 rearranged to the C-nucleoside 4 and 16.
Keywords Acyclic C-nucleosides; Beginelli reaction; ß-diketones; microwave-assisted
synthesis; pyrimidinones
INTRODUCTION
Recent work has demonstrated the feasibility of using acyclic nucleoside
analogues as antiviral chemotherapeutic agents. The acyclic purine
derivatives have been the most widely studied.[1–4] For instance, (S)-9-(2,3-
dihydroxypropyl)adenine ((S)-DHPA),[5] the potent antiherpetic drug[6,7]
acyclovir (ACV, Zovirax),[8,9] 9-(2-phosphonylmethoxyethyl)adenine
(PMEA),
(S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)
adenine
(HPMPA),[10] (RS)-9-[4-hydroxy-2-(hydroxymethyl) butyl]guanine (HBG),
and 9-[(1,3-dihydroxy-2-propoxy)methyl] guanine (DHPG),[11,12] are
examples of such potent antiviral agents against a number of DNA and
Received 25 August 2008; accepted 3 February 2009.
Address correspondence to Najim A. Al-Masoudi, Chemistry Department, College of Science,
University of Basrah, Iraq. E-mail: Najim.Al-Masoudi@gmx.de
175

176
N. A. Al-Masoudi et al.
RNA viruses. Structure-activity relationship studies have shown that the side
chains of acyclonucleosides play a crucial role in the interaction of the
acyclonucleosides with their antiviral target enzymes.[13] In order to expand
our research on the modification of acyclic nucleosides[14–19] and to obtain
these building blocks in higher yields with shorter reaction times and
under milder reaction conditions, we turned our attention to microwave
irradiation (MWI). Herein, we report a rapid, facile, and practical protocol
for the formation of acyclic C-nucleosides of dihydropyrimidine, imidazole,
and pyridine bases derived from 1,2- and 1,3-diketones.
RESULTS AND DISCUSSION
The synthesis of dihydropyrimidinones has been presented in recent
years, because of their diverse pharmacological activities (such as antiviral,
antibacterial, and antihypertensive activity) as well as their efficacy as
calcium channel blockers and α-antagonists.[20,21] By following recent re-
ported work[22,23] on dihydropyrimidinones based on the Biginelli reaction,
we developed and present here a convenient and efficient one-pot synthesis
of the acyclic C-nucleosides having dihydropyrimidinone, imidazole, and
indene-1,3-dione bases. Thus, treatment of ( )-2,2-dimethyl-[1,3]dioxolan-
4-carbaldehyde (1)[24] with ethyl acetoacetate (2) and urea using the
triflate catalyst (TMSTMf) under MWI at 65◦C afforded (R and S)-3 (41%)
resulting from the formation of the stereocenter at C-4 of the DHPM
ring. Alternatively, 3 was prepared in a better yield (36%) under the same
conditions but using natural phosphate doped with ZnCl2 instead of the
triflate catalyst. The structure of 3 was assigned by NMR and its mass
spectrum [m/z: C10H16N2O5 (244.24) 245 (M+H+)]. 1H NMR of 3 showed
ꢁ
a doublet of doublets at δ 6.95 ppm (J 1 ,4 = 3.0 Hz, J NH,4 = 3.1 Hz) that was
attributed to H-4, since H-1ꢁ, H-2ꢁa and H-2ꢁb were oriented as multiplets at
the region δ 3.89–3.52 ppm. In the 13C NMR of 3, a signal at δ 55.8 ppm was
assigned to C-4.
Interestingly, treatment of 3 with NaOMe in MeOH under MWI at
100◦C for 5 minutes furnished a product that was tentatively identified as
6-(1,2-dihydroxyethyl)-pyrimidin-2-one (4) (45%). The structure of 4 was
assigned by HBMC NMR experiment, where C-6 at δ 147.1 ppm showed
2
a J C,H coupling with H-5 at δ 6.46 ppm and H-1ꢁ at δ 3.95 ppm. The
spectrum was also characterized by elimination of the CO2Et group at C-5 of
3, indicative of H-4 abstraction by action of methoxide ion and simultaneous
loss of water, leading to the formation of 4.
Kidwai et al.[25] had recently synthesized the trisubstituted imidazole
derivatives from condensation of benzil with aldehydes in excess of NH4OH
under MWI. In our hands, compound 1 has also turned out to be a useful
intermediate for the preparation of other model of C-acyclic nucleoside,

Microwave-Assisted Synthesis of Acyclic C-Nucleosides
177
SCHEME 1 Reagents and conditions: (i) 2, CF3SO2SiMe3 (TMSTMf), MWI, 65◦C, 25, min, pyridine
NH2CONH2; (ii) ZnCl2, natural phosphate (NP), MWI 45◦C, DMF, NH2CONH2; (iii) NaOMe-MeOH,
MWI, 100◦C, 5 min; (iv) 5 or 8, NH4OH, DMF, MWI, 100◦C, 10 min; (v) 80% HOAc, 80◦C, 1 h
following Kidawai’s method under MWI. Thus, treatment of 1 with benzil in
the presence of NH4OH at 100◦C for 10 minutes afforded, after purification,
6 (87%). The 1H NMR spectrum of 6 showed a doublet of doublets at δ 5.02
ppm was attributed to H-1ꢁ (J 1 ,2 a = 9.0 Hz, J 1 ,2 b = 3.1 Hz), whereas the
ꢁ
ꢁ
ꢁ
ꢁ
multiplet at δ 4.33–4.08 was assigned to H-2ꢁa and H-2ꢁb. Further, HMQC
2
NMR study of 6 revealed a J C,H coupling between C-2ꢁ at δ 74.6 ppm and
H-1ꢁ at δ 5.02 ppm.
An efficient and expeditious synthesis of the C-acyclic nucleoside of
new indeno[1,2-b]pyridine derivative was also accomplished using MWI.
Treatment of 1 with 1,3- indene-1,3-dione 8 in the presence of NH4OAc
under MWI at 100◦C for 10 minutes afforded, after chromatographic
purification, 9 (52%). The structure of 9 was identified by the NMR and
mass spectra. In the HMQC spectrum, H-2 and H-3 appeared as two doublets
at δ 8.69 and 8.01 ppm (J 2,3 = 9.1 Hz), respectively, and they demonstrated
2/3
J
correlations with C-4 at δ 145.1 ppm. Furthermore, C-4 showed a
C,H
2J C,H correlation with H-1ꢁ at δ 5.12 ppm.
Acid hydrolysis of 6 and 9 by 80% HOAc in 80◦C furnished the free
C-nucleosides 7 and 10 in 76 and 81% yields, respectively. All the schematic
pathways are outlined in Scheme 1.
Next, we expanded the scope of this microwave-assisted reaction to pre-
pare a new C-nucleoside with a pyridine residue by following the Hantzch
approach.[26] Thus, treatment of equimolar amounts of D-glyceraldehyde

178
N. A. Al-Masoudi et al.
SCHEME 2 Reagents and conditions: (i) NH4NO3, bentonite, MWI, 95◦C, 20 min; (ii) NaOMe-MeOH,
MWI, 85◦C, 15 min
(11) with methyl acetoacetate (2) and dimedone (3) in the presence
of bentonite clay as a support, NH4NO3 as the source of NH3, HNO3
as oxidant furnished, after chromatographic purification, 14 (45%). The
product of this reaction was a 1,4-dihydropyridine, which could be oxidized
to the corresponding pyridine derivative 15 (Scheme 2).[27] The structure
of 14 was confirmed from the NMR and mass spectra. In the HMQC
2
NMR spectrum, CH2–6 protons at δ 2.46 ppm was identified from its J C,H
correlation with C-5 at δ 198.3 ppm as well as a 2,3J CH correlation with C-8 at
δ 46.9 ppm and C-4a at δ 129.0 ppm. H-1ꢁ appeared as a multiplet at δ 4.57
ppm, whereas H-2ꢁa, H-2ꢁb, OMe and the hydroxyl groups were oriented as
multiplets in the region at δ 4.14–3.69 ppm.
Treatment of 14 with NaOMe under MWI in MeOH at 85◦C
for 15 min resulted in the formation of a new compound with a molecular
ion of m/z: C16H19NO4 (312) (M+Na)+, which was identified as methyl
2-(hydroxymethyl)-4,7,7-trimethyl-6,7-dihydro-2H-furo[4,3,de]quinoline-3-
carboxylate (16) (45%). The possible mechanism of formation of 16 might
be explained in term of the formation of intermediate 15 as a result of
H-6 elimination by methoxide ion, followed by loss of H2O under MWI at
85◦C. In the HMQC NMR spectrum of 16, H-8 at δ 4.54 ppm showed a 3J C,H
correlation with C-1a at δ 124.9 ppm, and the latter showed the correlation
with H-2ꢁ at δ 4.85 ppm.
The formation of the furan ring was identified from the subsequent
3J CH correlation between H-2ꢁ at δ 4.85 ppm and C-1 at δ 149.7 ppm. The
two singlets at δ 2.53 and 3.65 ppm were assigned to C4-Me and CH2–6,
respectively. Furthermore, the large shifts in δ values of the C O groups at

Microwave-Assisted Synthesis of Acyclic C-Nucleosides
179
δ 198.3 ppm (compound 14) and C-1 at δ 149.7 ppm (compound 16) was
indicative of the formation of a furan group via the intermediate 15.
EXPERIMENTAL
Microwave supported reactions were performed in a SmithSynthesizer
(Personal Chemistry AB, monomode microwave cavity at 2.45 GHz, tem-
perature control by automated adjustment of irradiation power in a range
from 0 to 300 W) in Biotage microwave reaction vials (2–5 mL) with Teflon
septum and an aluminum crimp top. Melting points are uncorrected and
were measured on a Bu¨chi melting point apparatus B-545 (Bu¨chi Labortech-
nik AG, Switzerland). Microanalytical data were obtained with a Vario,
Elementar apparatus (Shimadzu, Japan). NMR spectra were recorded on
600 MHz (1H) and at 62.9 MHz (13C) on spectrometers (Bruker, Germany)
with TMS as internal standard and on δ scale in ppm. Heteronuclear
1
assignments were verified by H-13C HMBC experiment. Mass spectra were
recorded at 70 eV on EI and FAB mass spectra were measured on a
MAT 8200 spectrometer (Finnigan MAT, USA) using 3-nitrobenzyl alcohol
(NBOH) or glycerol as matrices.
Ethyl 4-((R and S)-1,2-dihydroxyethyl-6-methyl-2-oxo-1,2,3,4-
tetrahydropyrimidine 5-carboxylate (3)
Method A
A suspension of racemic mixture 1 (130 mg, 1.00 mmol), urea (180 mg,
3.00 mmol), ethyl acetoacetate (2) (130 mg, 1.00 mmol), and trimethylsilyl
trifluoromethanesulphonate (TMSTf) (222 mg, 1.00 mmol) in pyridine (10
mL) was stirred under MWI at 65◦C for 25 minutes. After cooling, the
mixture was triturated with few drops of MeOH, then co-evaporated with
toluene (4 × 20 mL) and EtOH (3 × 20 mL). The residue was co-evaporated
in MeOH (5 mL) with silica gel (2 g), then poured onto a column of silica
gel (5 g) using a gradient of MeOH (0–20%) and CHCl3 as eluent to give (R
and S)-3 (100 mg, 41%), as amorphous solid. 1H NMR (DMSO-d6): δ 7.21 (s,
ꢁ
1H, NH); 6.95 (d, 1H, J 1 ,4 = 3.0 Hz, J 4,NH = 3.1 Hz, H-4); 4.05 (q, 2H, J =
7.1 Hz, OCH2CH3); 3.89–3.52 (m, 5H, H-1ꢁ, H-2ꢁa. H-2ꢁb, OH); 1.12 (t, 3H,
OCH2CH3). 13C NMR (DMSO-d6): δ 165.9 (COOEt); 152.6 (CONH); 148.9
(C-6); 95.2 (C-5); 73.9 (C-1ꢁ); 63.5 (C-2ꢁ); 60.9 (OCH2CH3); 55.8 (C-4); 17.8
(C6-Me); 14.1 (OCH2CH3). Anal. calc, for C10H16N2O5 (244.24): C, 49.17;
H, 6.60; N, 11.47. Found: C, 48.93; H, 6.52; N, 11.25. MS: m/z (FAB) 245
(M+H)+.

180
N. A. Al-Masoudi et al.
Method B
Compound 3 was prepared by following the same procedure in method
a, using the catalyst ZnCl2/neutral phosphate (2.0 g) instead of TMSTMf.
Yield: 88 mg (36%). The NMR and other physical properties were identical
to those for the compound prepared in method a.
Reaction of 3 with Sodium Methoxide
A solution of 3 (200 mg, 0.82 mmol) in 0.2 M NaOMe solution (10 mL)
was stirred under MWI for 10 min at 100◦C. The solution was neutralized
with HOAc and then evaporated to dryness. The residue was worked up
as in experiment 3 to give a compound that was identified as 4 (63 mg,
1
45%); m.p. 139–142◦C. H NMR (DMSO-d6): δ 7.79 (s, 1H, NH); 6.46 (s,
1H, H-5); 3.95 (dd, 1H, J 1 ,2a = 8.9 Hz, J 1 ,2b = 3.0 Hz, H-1ꢁ); 3.82 (dd, 1H,
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
J 2a ,2b = 11.0 Hz, H-2 a); 3.63 (m, 2H, H-2 b, C5 -OH); 2.21 (s, 3H, Me).
13C NMR (DMSO-d6): δ 173.6 (C-4); 157.6 (C O); 147.1 (C-6); 100.8 (C-5);
80.9 (C-1ꢁ); 61.0 (C-2ꢁ). 24.5 (C4-Me). Anal. calc. for C7H10N2O3 (170.17): C,
49.41; H, 5.92; N, 16.46. Found: C, 49.20; H, 5.85; N, 16.20. MS: m/z (FAB)
171 (M+H)+.
( )-2-(2,2-Dimethyl-[1,3]dioxolan-4-yl)-4,5-diphenyl-1H-imidazole (6)
A mixture of 1 (0.65 g, 5.00 mmol) benzyl, (1.05 g, 5.00 mmol),
and NH4OAc (0.63 g, 18.00 mmol) was stirred under MWI at 100◦C for
5 minutes. After cooling, the residue was worked up as in the previous
experiment to give 6 (1.48 g, 87%); m.p. 141–144◦C. 1H NMR (DMSO-d6):
ꢁ
ꢁ
δ 12.95 (s, 1H, NH); 7.55–7.43 (m, 10H, Ar-H); 5.02 (dd, 1H, J 1 ,2 a = 9.0 Hz,
J 1 ,2 b = 3.1 Hz, H-1ꢁ); 4.33–4.08 (m, 2H, H-2ꢁa, H-2bꢁ); 1.41 (s, 6H, 2CMe2).
13C NMR (DMSO-d6): δ 145.9 (C-2); 136.5 (Carom); 129.1, 128.5, 127.9, 127.2
(Carom + C-4 + C-5); 120.8 (CMe2); 84.5 (C-1ꢁ); 74.6 (C-2ꢁ); 26.1 (CMe2).
Anal. calc. for C20H20N2O2 (320.38): C, 74.98; H, 6.29; N, 8.74. Found: C,
74.71; H, 6.20; N, 8.52. MS: m/z (FAB) 321 (M+H)+.
ꢁ
ꢁ
1-(4,5-Diphenyl-1H-imidazol-2-yl)ethane-1,2-diol (7)
A solution of 6 (100 mg, 0.31 mmol) in 80 HOAc (5 mL) was kept at
80◦C for 1 hour. After cooling, the solution was evaporated to dryness, and
the residue was co-evaporated with EtOH (4 × 10 mL). The residue was
purified on a short column of silica gel (5 g) using CHCl3-MeOH (9:1)
1
as the eluent to give 7 (237 mg, 76%), as an amorphous solid. H NMR
(DMSO-d6): 12.85 (s, 1H, NH); 7.53–7.40 (m, 10H, Ar-H); 4.50 (m, 1H,
H-1ꢁ); 4.08–3.60 (m, 5H, H-2ꢁa, H-2ꢁb, OH). 13C NMR (DMSO-d6): δ 146.2
(C-2); 137.1 (Carom); 129.3, 128.6, 127.8, 127.3 (Carom + C-4 + C-5); 78.1
(C-1ꢁ); 65.2 (C-2ꢁ). Anal. calc. for C17H16N2O2 (280.32): C, 72.84; H, 5.75;
N, 9.99. Found: C, 72.62; H, 5.62; N, 9.78. MS: m/z (FAB) 303 (M+Na)+.

Microwave-Assisted Synthesis of Acyclic C-Nucleosides
181
4-(2,2-Dimethyl-1,3-dioxolan-4-yl)-9H-indeno[1,2-b]pyridin-9-one (9)
This compound was prepared from 1 (0.35 g, 2.69 mmol), 1H-indene-
1,3-dione (8) (0.73 g, 5.00 mmol), and NH4OAc (0.63 g, 18.00 mmol)
following the same procedure for preparation of 6. Yield: 0.39 g (52%); m.p.
144–148◦C. 1H NMR (DMSO-d6): δ 8.75 (dd, 1H, J 7,8 = 8.8 Hz, J 6,8 = 2.9 Hz,
H-8); 8.69 (d, 1H, J 2,3 = 9.1 Hz, H-2); 8.38 (dd, 1H, J 5,6 = 8.9 Hz, J 5,7 = 2.8
ꢁ
ꢁ
Hz, H-5); 8.01 (dd, 1H, H-3); 7.69–7.51 (m, 2H, Ar-H); 5.12 (dd, 1H, J 1 ,2a
= 9.0 Hz, J 1 ,2b = 2.9 Hz, H-1ꢁ); 4.30–4.00 (m, 2H, H-2ꢁ, H-4aꢁ); 1.40 (s, 6H,
2CMe2). 13C NMR (DMSO-d6): δ 186.3 (C O); 152.2 (C N); 145.1 (C-4);
143.3 (C-2 + C-5a); 134.0 (C-8a); 133.0 (C-6); 130.2 (C-3), 129.2, 128.6 (C-7
+ C-8); 120.5 (CMe2); 83.9 (C-1ꢁ); 73.9 (C-2ꢁ); 26.1 (CMe2). Anal. calc. for
C17H15NO3 (281.31): C, 72.58; H, 5.37; N, 4.98. Found: C, 72.34; H, 5.19; N,
4.73. MS m/z (FAB) 282 (M+H)+.
ꢁ
ꢁ
4-(1,2-Dihydroxyethyl)-9H-indeno[1,2-b]pyridin-9-one (10)
This compound was prepared from 9 (120 mg, 0.43 mmol) following
the same procedure for preparation of 7. Yield: 84 mg (81%); m.p.
152–155◦C. 1H NMR (DMSO-d6): δ 8.72 (dd, 1H, J 7,8 = 8.7 Hz, J 6,8 = 2.8
Hz, H-8); 8.69 (d, 1H, J 2,3 = 9.0 Hz, H-2); 8.40 (dd, 1H, J 5,6 = 8.9 Hz,
J 5,7 = 2.8 Hz, H-5); 8.05 (dd, 1H, H-3); 7.70–7.52 (m, 2H, Ar-H); 4.54 (m,
1H, H-1ꢁ); 4.29–3.87 (m, 4H, H-2ꢁa, H-2bꢁ, OH). 13C NMR (DMSO-d6): δ
186.7 (C O); 153.1 (C N); 143.4 (C-2 + C-5a); 134.1 (C-8a); 132.8 (C-6);
130.4 (C-3), 129.1, 128.5 (C-7 + C-8); 72.1 (C-1ꢁ); 64.9 (C-2ꢁ). Anal. calc. for
C14H11NO3 (241.24): C, 69.70; H, 4.60; N, 5.81. Found: C, 69.51; H, 5.52; N,
5.61. MS m/z (FAB) 264 (M+Na)+.
Methyl 4-(1,2-dihydroxyethyl)-2,7,7-trimethyl-5-oxo-5,6,7,8-tetrahydro-
quinoline-3-carboxylate (14)
A mixture of D-glyceraldehyde (11) (0.27 g, 3.00 mmol), methyl ace-
toacetate (12) (0.35 g, 3.00 mmol), dimedone (13) (0.42 g, 3.00 mmol),
and NH4NO3 (0.24 g, 3.00 mmol) was stirred with bentonite (0.50 g) under
MWI at 95◦C for 20 minutes. After cooling, the mixture was co-evaporated
with EtOH (4 × 10 mL), and the residue was dissolved in MeOH and
co-evaporated with SiO2 (1 g). The residue was poured onto a column of
silica gel (5 g) and eluted, in gradient, with MeOH (0–20%) and CHCl3
1
to give 14 (0.31 g, 32%), as an amorphous. H NMR (DMSO-d6): δ 4.57
(m, 1H, H-1ꢁ); 4.14–3.69 (m, 7H, H-2ꢁa, H-2bꢁ, OMe, 2xOH); 2.98 (s, 2H,
CH2–8); 2.53 (s, 3H, C2-Me); 2.46 (m, 2H, CH2–6); 1.28 (s, 6H, C7-Me2).
13C NMR (DMSO-d6): δ 198.3 (C5 O); 169.1 (C N); 166.8 (CO2Me); 160.1
(C-2); 152.5 (C-4); 129.0 (C-4a); 120.8 (C-3); 70.1 (C-1ꢁ); 65.2 (C-2ꢁ); 52.8
(C-6); 50.9 (CO2Me); 46.9 (C-8); 28.0 (C7-Me2); 21.7 (C2-Me). Anal. calc. for
C16H21NO5 (307.34): C, 62.53, H, 6.89, N, 4.56. Found: C, 62.31, H, 6.80, N,
4.21. MS m/z (FAB) 308 (M+H)+.

182
N. A. Al-Masoudi et al.
Reaction of 14 with NaOMe
A solution of 14 (100 mg, 0.31 mmol) in 0.2 M NaOMe solution
(10 mL) was stirred under MWI for 15 minutes at 85◦C. The solution
was neutralized with HOAc and then evaporated to dryness. The residue
was worked up as in experiment 3 to give compound that was identified
as methyl 2-(hydroxymethyl)-4,7,7-trimethyl-6,7-dihydro-2H-furo[4,3,de]quinoline-
1
3-carboxylate (16) (42 mg, 45%), m.p. 128–131◦C. H NMR (DMSO-d6): δ
4.85 (m, 1H, H-2ꢁ);4.54 (s, 1H, H-8); 4.31–4.03 (m, 2H, H-3ꢁa, H-3ꢁb); 3.88
(s, 3H, CO2Me); 3.62 (m, 1H, OH); 3.65 (s, 2H, CH2–6); 2.52 (s, 3H, C4-Me);
1.24 (s, 6H, C7-Me2). 13C NMR (DMSO-d6): δ 167.1 (CO2Me); 164.2 (C N);
160.7 (C-4); 149.7 (C-1 + C-2); 124.9 (C-1a); 120.8 (C-3); 106.3 (C-8); 98.4
(C-2ꢁ); 57.8 (C-3ꢁ); 52.2 (C-6); 50.3 (CO2Me); 28.9 (C7-Me2); 26.8 (C-7); 21.7
(C4-Me). Anal. calc. for C16H19NO4 (289.13): C, 66.42, H, 6.62, N, 4.84.
Found: C, 66.20, H, 6.54, N, 4.61. MS m/z (FAB) 312 (M+Na)+.
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