Synthesis of [5,6]-fused pyridocoumarins through aza-Claisen rearrangement of 6-propargylaminocoumarins

Article abstract of DOI:10.1016/j.tetlet.2011.08.012

[5,6]-Fused pyridocoumarins are prepared through aza-Claisen rearrangement and subsequent in situ cyclization of 6-propargylaminocoumarins under microwave irradiation in the presence of boron trifluoride diethyl etherate in N,N-dimethylformamide. During this process demethoxycarbonylation is observed in the corresponding 4-carbomethoxycoumarin derivatives.

Full text of DOI:10.1016/j.tetlet.2011.08.012

Tetrahedron Letters 52 (2011) 5452–5455
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Tetrahedron Letters
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Synthesis of [5,6]-fused pyridocoumarins through aza-Claisen rearrangement
of 6-propargylaminocoumarins
⇑
Theodoros S. Symeonidis, Michael G. Kallitsakis, Konstantinos E. Litinas
Laboratory of Organic Chemistry, Department of Chemistry, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece
a r t i c l e i n f o
a b s t r a c t
Article history:
[5,6]-Fused pyridocoumarins are prepared through aza-Claisen rearrangement and subsequent in situ
cyclization of 6-propargylaminocoumarins under microwave irradiation in the presence of boron trifluor-
ide diethyl etherate in N,N-dimethylformamide. During this process demethoxycarbonylation is observed
in the corresponding 4-carbomethoxycoumarin derivatives.
Received 15 June 2011
Revised 25 July 2011
Accepted 2 August 2011
Available online 7 August 2011
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Pyrido[5,6]coumarins
MW irradiation
Propargylation
[7,8]-Fused pyrido[5,6]coumarins
Claisen rearrangement
Coumarin derivatives are an interesting class of heterocyclic
system since the coumarin ring is an essential core moiety in a
variety of natural and synthetic biologically active compounds.1–7
In particular fused coumarins, among them pyridocoumarins, have
been reported to possess antiallergic,8 antidiabetic,9 analgesic,10,11
antiinflammatory,11 and antimicrobial11 properties.
Pyridine derivatives have also been prepared by electrophilic
cyclization of propargylamines in the presence of gold,30 cop-
per30,31 or mercury32 salts. Propargylamines, on aza-Claisen rear-
rangement33–35 resulted in pyrrole36–38 or dihydropyridine39,40
derivatives. Decomposition31 occurred during acid-catalyzed rear-
rangement of propargylamines at 100 °C. BF3ꢀEt2O has been used
for the aza-Claisen rearrangement of N-allylanilines to o-allylani-
lines under heating41,42 or microwave irradiation in xylenes.43 Re-
cently,44 we reported on the Claisen rearrangements of reactions of
propargyloxycoumarins under microwave irradiation, which in the
presence of BF3ꢀEt2O in DMF resulted in pyranocoumarins, while
with N-methylformamide (NMF) gave furocoumarins. In the course
of our investigations on the synthesis21,25 of fused pyridocoumarin
derivatives in order to study further their biological activities, we
report here on the application of BF3ꢀEt2O in the synthesis of the ti-
tle compounds from 6-propargylaminocoumarins. The reactions
studied and the products obtained are depicted in Schemes 1–3.
Propargylation of 6-aminocoumarin (1a)45 with propargyl bro-
mide (2) in dry acetone in the presence of K2CO3 under reflux for
5 days gave 6-propargylaminocoumarin (3a) (54%) and 6-(dip-
ropargylamino)coumarin (4a) (8%), while 33% of the starting mate-
rial remained unreacted (Scheme 1). Microwave irradiation of a
solution of compound 3a in BF3ꢀEt2O and DMF at 200 °C for 9 h
(the mixture was monitored by TLC every hour) resulted in the
3H-pyrano[3,2-f]quinolin-3-one (5a)16,27 (38%), while 49% of the
starting material remained unchanged. Analogous propargylation
of 6-amino-7-methylcoumarin (1b)46 led to 7-methyl-6-propa-
rgylaminocoumarin (3b) (56%) (38% of the starting amine
The synthesis of pyridocoumarins has been achieved either by
formation of the pyridine7,9–22 or the pyranone7,23–29 moieties.
Construction of the pyridine moiety involves iodocyclization of
6-(but-2-ynyl)aminocoumarin in the presence of I2, a process
developed by Majumdar et al.,12 the Pd-catalyzed Heck cycliza-
tion13–15 of (20-bromo)benzylaminocoumarins to dihydropyri-
do[3,2-g]- or [2,3-c]coumarins, the Skraup reaction16 on 6-
nitrocoumarin, the reactions of aminocoumarins with glycerol,17
malondialdehyde,18 ethyl benzoylacetate,19 alkyl vinyl ketones10
or under Vilsmeier conditions,20 the Diels–Alder reactions of the
O-methyl imine of 2-oxo-2H-chromene-4-carboxaldehyde with
dienophiles21 and reactions of 4-oxo-4H-chromene-3-carbalde-
hyde with enamines.9,22 The formation of the pyranone moiety is
realized from quinolinols by Pechmann condensation23,24 or reac-
tions25 with DMAD and PPh3, from quinolinequinones via Wittig
reactions25 or condensation with diethyl aminofumarate,26 by the
oxidation of a pyran ring formed in situ by electrocyclization of
cis-dienals27 and demethylation and condensation of o-substituted
(20-methoxyphenyl)pyridine carboxylic acids.28,29
⇑
Corresponding author. Tel.: +30 2310997864; fax: +30 2310997679.
E-mail address: klitinas@chem.auth.gr (K.E. Litinas).
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.08.012

T. S. Symeonidis et al. / Tetrahedron Letters 52 (2011) 5452–5455
5453
H
H2N
R
N
N
i
+
O
O
O
O
O
O
R
1a,b
3a,b
4a
ii
1,3,5 a
: R=H
b: R=CH3
N
O
O
R
5a,b
Scheme 1. Reagents and conditions: (i) Propargyl bromide (2), K2CO3, acetone (dry), reflux, 5 d; (ii) BF3ꢀEt2O, DMF, MW, 200 °C, 9 h.
R
O
R
O
O2N
iii
iv
i
O
O
OH
or
ii
7a,b
8a,b
6
R
O
R
O
H
N
H2N
N
v
vi
O
O
O
O
9a,b
11
10a,b
7-10a:
R=H
b: R=COOMe
Scheme 2. Reagents and conditions: (i) Ethyl propynoate, TFA, Pd(OAc)2 (1.25 mol %), 0 °C (5 min) then rt (24 h) (for 7a); (ii) Ph3P, DMAD, CH2Cl2, 0 °C (10 min) then reflux
(48 h) (for 7b); (iii) concd H2SO4 (cooling, stirring 30 min), KNO3, rt 24 h; (iv) HCOOH, Et3N, 10% Pd/C, 100 °C, 20 min; (v) propargyl bromide (2), K2CO3, acetone (dry), reflux,
5 d; (vi) BF3ꢀEt2O, DMF, MW, 200 °C, 2.5 h.
COOMe
COOMe
O2N
O2N
H2N
ii
i
O
O
OH
O
O
13
14
12
MeOOC
H
N
N
iii
iv
O
O
O
O
15
16
Scheme 3. Reagents and conditions: (i) Ph3P, DMAD, toluene, 0 °C (10 min) then reflux (3 d); (ii) HCOOH, Et3N, 10% Pd/C, 100 °C, 20 min; (iii) propargyl bromide (2), K2CO3,
DMF (dry), 70 °C, 48 h; (iv) BF3ꢀEt2O, DMF, MW, 200 °C, 3 h.
remained unreacted), which on microwave irradiation gave the
pyridocoumarin 5b47 in 50% yield (22% of 3b remained unreacted).
The fused coumarin 7a was isolated47 in 80% yield from the
reaction48 of a solution of 5,6,7,8-tetrahydro-1-naphthol (6) in
TFA with ethyl propynoate in the presence of a catalytic amount
of Pd(OAc)2. Nitration46 of coumarin 7a with KNO3 in H2SO4 re-
sulted in nitrocoumarin 8a (78%). In the NOE experiments on
compound 8a there was a 2% interaction between H-4 and H-5
which helped to confirm the structure.
Reduction46 of the nitro compound 8a with HCOOH/Et3N in the
presence of 10% Pd/C at 100 °C gave the amine 9a (77%) (Scheme 2).
Treatment of 9a in refluxing acetone for 5 days with propargyl bro-
mide (2) and K2CO3 led to propargylamino derivative 10a (59%).
The fused pyridocoumarin 11 (60%) was obtained by microwave

5454
T. S. Symeonidis et al. / Tetrahedron Letters 52 (2011) 5452–5455
H
H
HN
HN
HN
(i)
(ii)
O
O
O
O
O
O
3a
B
A
HN
HN
N
(iii)
(iv)
O
O
O
O
O
O
D
5a
C
Scheme 4. (i) [3,3] Rearrangement; (ii) [1,5-H] sigmatropic shift; (iii) 6n-electrocyclization; (iv) oxidation.
2. O’Kennedy, R.; Thornes, R. D. In Coumarins: Biology, Applications and Mode of
Action; J. Wiley & Sons: Chichester, 1997.
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Pharm. Des. 2004, 10, 3813.
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2004, 11, 3239.
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2795.
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1994, 30, 867.
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13. Majumdar, K. C.; Nath, S.; Chattopadhyay, B.; Sinha, B. Synthesis 2010, 3918.
14. Majumdar, K. C.; Chattopadhyay, B.; Nath, S. Tetrahedron Lett. 2008, 49, 1609.
15. Majumdar, K. C.; Chattopadhyay, B.; Taher, A. Synthesis 2007, 3647.
16. Liska, K. J.; Fentiman, A. F.; Foltz, R. L. Tetrahedron Lett. 1970, 11, 4657.
17. Petrow, V.; Rewald, E. L. J. Chem. Soc. 1949, 769.
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21. Gautam, D. R.; Protopappas, J.; Fylaktakidou, K. C.; Litinas, K. E.; Nicolaides, D.
N.; Tsoleridis, C. A. Tetrahedron Lett. 2009, 50, 448.
22. Ghosh, C. K.; Ray, A.; Patra, A. J. Heterocycl. Chem. 2001, 38, 1459.
23. Sethna, S. M.; Phadke, R. Org. React. 1953, 7, 1.
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Abstr. 1951, 45, 7125e..
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2007, 63, 8298.
26. Fajgelj, S.; Golic, L.; Stanovnik, B.; Tisler, M. Heterocycles 1994, 37, 847.
27. Hon, Y.-S.; Tseng, T.-W.; Cheng, C.-Y. Chem. Commun. 2009, 5618.
28. O’Callaghan, C. N. Synthesis 1987, 499.
irradiation of a solution of 10a in DMF in the presence of BF3ꢀEt2O
at 200 °C for 2.5 h.
4-Carbomethoxycoumarin 7b (71%) was prepared from the
reaction25 of naphthol 6 with dimethylacetylenedicarboxylate
(DMAD) in the presence of PPh3. Nitration of compound 7b in anal-
ogy to 7a resulted in nitrocoumarin 8b (79%), which was reduced
to amine 9b (78%). Propargylation of the latter led to the propa-
rgylaminocoumarin derivative 10b (63%), which on microwave
irradiation at 200 °C with BF3ꢀEt2O in DMF for 2.5 h gave again
the pyridocoumarin 11 (52%) after demethoxycarbonylation of
the intermediate ester. This ester hydrolysis and subsequent decar-
boxylation possibly occurred after formation of the pyridine ring.
This is similar to demethoxycarbonylation of methyl carboxylates
in quinoline in the presence of Cu at 170–175 °C.49
The 6-nitrocoumarin derivative 13 was synthesized from the
reaction25 of 4-nitro-1-naphthol (12) with DMAD and PPh3 in tol-
uene in 85% yield. Reduction46 of nitro compound 13 as before gave
the amine 14 (85%). The propargylaminocoumarin 15 was obtained
in 53% yield from the reaction of amine 14 with propargyl bromide
(2) in the presence of K2CO3 by heating in DMF at 70 °C for 48 h
(36% of 14 was recovered). Treatment of derivative 15 with
BF3ꢀEt2O in DMF at 200 °C for 3 h under microwave irradiation gave
2H-benzo[h]pyrano[3,2-f]quinolin-2-one
(16)
(42%),
again
demethoxycarbonylation occured.
A mechanistic proposal involving aza-Claisen rearrangement for
the transformation of propargylaminocoumarins into fused pyr-
idocoumarins in analogy to the Claisen rearrangement of propa-
rgyloxycoumarins44 is shown in Scheme 4. Initial [3,3]-
rearrangement of propargylaminocoumarin 3a gave allenyl inter-
mediate A, which undergoes aromatization to the o-aminoallenyl
derivative B. A [1,5-H]-shift in B led to C, which cyclized to the
dihydropyridine derivative D. Oxidation of the latter under the
reaction conditions afforded pyridocoumarin 5a.
In conclusion, we have demonstrated the use of boron trifluor-
ide diethyl etherate under microwave irradiation conditions for the
formation of pyridocoumarin derivatives in moderate to good
yields.
29. Chatterjea, J. N.; Shaw, S. C.; Prasad, Y.; Singh, R. P. J. Indian Chem. Soc. 1984, LXI,
1028.
30. Abbiati, G.; Arcadi, A.; Bianchi, G.; Di Giuseppe, S.; Marinelli, F.; Rossi, E. J. Org.
Chem. 2003, 68, 6959.
31. Barmettler, P.; Hansen, H.-J. Helv. Chim. Acta 1990, 73, 1515.
32. Zhang, X.; Yao, T.; Campo, M. A.; Larock, R. C. Tetrahedron 2010, 66, 1177.
33. Majumdar, K. C.; Bhattacharyya, T.; Chattopadhyay, B.; Sinha, B. Synthesis 2009,
2117.
34. Martin-Castro, A. M. Chem. Rev. 2004, 104, 2939.
35. Nubbemeyer, U. Top. Curr. Chem. 2005, 244, 149.
36. Cossy, J.; Poitevina, C.; Salle, L.; Gomez Pardo, D. Tetrahedron Lett. 1996, 37,
6709.
37. Frey, H. Synlett 1994, 1007.
Acknowledgments
38. Majumdar, K. C.; Chattopadhyay, B. Synthesis 2008, 921.
39. Majumdar, K. C.; Bhattacharyya, T. Tetrahedron Lett. 2001, 42, 4231.
40. Majumdar, K. C.; Samanta, S. K. Tetrahedron 2001, 57, 4955.
41. Majumdar, K. C.; Alam, S.; Chattopadhyay, B. Tetrahedron 2008, 64, 597.
42. Anderson, W. K.; Lai, G. Synthesis 1994, 1287.
43. Gonzalez, I.; Bellas, I.; Souto, A.; Rodriguez, R.; Cruces, J. Tetrahedron Lett. 2008,
49, 2002.
44. Litinas, K. E.; Symeonidis, T. S. Tetrahedron 2010, 66, 1289.
45. De, P. Synthesis 2004, 1835.
Part of this research (T. Symeonidis) was co-financed by the
European Union (European Social Fund—ESF) and Greek national
funds through the Operational Program ‘Education and Lifelong
Learning’ of the National Strategic Reference Framework (NSRF)—
Research Funding Program: Heracleitus II. Investing in knowledge
society through the European Social Fund.
46. Lin, S.-T.; Yang, F.-M.; Yang, H.-J.; Huang, K.-F. J. Chem. Res., (S) 1995, 372.
47. Procedures and selected data:
References and notes
(a) Synthesis of 7,8,9,10-tetrahydro-2H-benzo[h]chromen-2-one (7a). To an ice-
cold solution of compound 6 (0.296 g, 2 mmol) in TFA (2 ml) were added
Pd(OAc)2 (6 mg, 0.025 mmol) and ethyl propynoate (0.39 g, 0.41 ml, 4 mmol).
The mixture was stirred for 5 min under cooling, stirred for 22 h at room
1. Murray, D. H.; Mendez, J.; Brown, S. A. In The Natural Coumarins: Occurrence,
Chemistry and Biochemistry; J. Wiley & Sons: N. York, 1982.

T. S. Symeonidis et al. / Tetrahedron Letters 52 (2011) 5452–5455
5455
temperature and neutralized with 10% NaHCO3 solution. Extraction with
CH2Cl2 (2 ꢁ 50 ml), drying of the organic layer (MgSO4), evaporation of the
solvent and separation by column chromatography [silica gel, hexane/EtOAc
(5:1)] gave, after elution of unreacted starting material (5%), compound 7a
(80% yield), light-green crystals, mp 105–106 °C (CH2Cl2), IR (KBr): 1712,
(59% yield), white crystals, mp 92–93 °C (CH2Cl2), IR (KBr): 3379, 2125,
1705 cmꢂ1 1H NMR (300 MHz, CDCl3)
1.73–1.94 (m, 4H), 2.26 (t, 1H,
;
d
J = 2.0 Hz), 2.50 (t, 2H, J = 5.7 Hz), 2.92 (t, 2H, J = 5.7 Hz), 3.83 (br s, 1H), 4.01 (d,
2H, J = 2.0 Hz), 6.36 (d, 1H, J = 9.6 Hz), 6.56 (s, 1H), 7.67 (d, 1H, J = 9.6 Hz); 13C
NMR (75.5 MHz, CDCl3) d 21.7, 22.6, 33.8, 34.3, 41.1, 69.1, 83.2, 108.3, 117.2,
122.7, 125.9, 131.6, 137.4, 140.2, 144.9, 161.6; MS (ESI): 254 [M+H]+ꢀ, 276
[M+Na]+ꢀ; Anal. Calcd for C16H15NO2: C, 75.87; H, 5.97; N, 5.53. Found: C, 75.99;
H, 5.85; N, 5.61.
1604 cmꢂ1 1H NMR (300 MHz, CDCl3)
; d 1.75–1.94 (m, 4H), 2.98 (t, 2H,
J = 5.5 Hz), 3.04 (t, 2H, J = 5.5 Hz), 6.35 (d, 1H, J = 9.5 Hz), 7.01 (d, 1H, J = 7.7 Hz),
7.21 (d, 1H, J = 7.7 Hz), 7.66 (d, 1H, J = 9.5 Hz); 13C NMR (75.5 MHz, CDCl3) d
22.0, 22.4, 22.5, 29.9, 114.9, 124.3, 125.2, 125.5, 142.5, 143.9, 152.2, 155.0,
161.2; MS (ESI): 201 [M+H]+ꢀ, 223 [M+Na]+ꢀ; Anal. Calcd for C13H12O2: C, 77.98;
H, 6.04. Found: C, 77.72; H, 6.23.
(e) General procedure for the synthesis of pyridocoumarins from 6-
propargylaminocoumarins. To
a
solution of compound 10a (30 mg,
0.12 mmol) in DMF (1 ml), BF3ꢀEt2O (0.03 ml, 0.24 mmol) was added and the
mixture irradiated using a Biotage (Initiator 2.0) scientific microwave oven at
200 °C for 2.5 h (the mixture was monitored by TLC every 30 min). After
cooling, the mixture was poured into H2O (30 ml) and extracted with Et2O
(3 ꢁ 20 ml). The ether layer was dried (MgSO4), concentrated and separated by
column chromatography [silica gel, hexane/EtOAc (3:1)] to give unreacted
(b) Synthesis of 6-nitro-7,8,9,10-tetrahydro-2H-benzo[h]chromen-2-one (8a).
Coumarin 7a (0.3 g, 1.5 mmol) was added under stirring over 30 min to ice-
cold concentrated H2SO4 (2 ml). KNO3 (0.192 g, 1.91 mmol) was then added
and the mixture stirred for 24 h and neutralized with an ice-cold 10% NaHCO3
solution. The precipitated solid was filtered to give compound 8a (78%), brown
crystals, mp 138–140 °C (EtOAc), IR (KBr): 1743, 1613 cmꢂ1
;
1H NMR
starting
benzo[h]pyrano[3,2-f]quinolin-2-one 11 (60% yield), white crystals, mp 93–
94 °C (CH2Cl2), IR (KBr): 1702, 1645, 1612 cmꢂ1 1H NMR (300 MHz, CDCl3) d
material
(23%)
followed
by
9,10,11,12-tetrahydro-2H-
(300 MHz, CDCl3) d 1.86–1.89 (m, 4H), 2.98 (t, 2H, J = 6.5 Hz), 3.07 (t, 2H,
J = 6.5 Hz), 6.50 (d, 1H, J = 9.6 Hz), 7.71 (d, 1H, J = 9.6 Hz), 7.95 (s, 1H); 13C NMR
(75.5 MHz, CDCl3) d 20.8, 21.7, 23.2, 27.1, 115.6, 117.5, 121.4, 128.6, 136.9,
142.5, 145.9, 153.9, 159.5; MS (ESI): 268 [M+Na]+ꢀ; Anal. Calcd for C13H11NO4:
C, 63.67; H, 4.52; N, 5.71. Found: C, 63.54; H, 4.56; N, 5.73.
;
1.79–1.96 (m, 4H), 2.98–3.08 (m, 2H), 3.38–3.47 (m, 2H), 6.57 (d, 1H,
J = 9.8 Hz), 7.56 (dd, 1H, J1 = 4.2 Hz, J2 = 8.4 Hz), 8.41 (d, 1H, J = 9.8 Hz), 8.50
(d, 1H, J = 8.4 Hz), 8.97 (d, 1H, J = 4.2 Hz); 13C NMR (75.5 MHz, CDCl3) d 22.1,
22.3, 25.6, 29.8, 114.8, 121.9, 123.5, 128.6, 129.7, 138.7, 142.1, 146.2, 148.6,
152.6, 154.8, 159.5; MS (ESI): 252 [M+H]+ꢀ, 274 [M+Na]+ꢀ; Anal. Calcd for
(c) Synthesis of 6-amino-7,8,9,10-tetrahydro-2H-benzo[h]chromen-2-one (9a).
Nitrocoumarin 8a (0.245 g, 1 mmol) was added under stirring to a mixture of
Et3N (8 ml), HCOOH (1 ml) and 10% Pd/C (28 mg, 0.45 mmol). The resulting
mixture was then heated at 100 °C for 20 min, poured onto ice (10 g) and
extracted with CH2Cl2 (7 ꢁ 30 ml). The organic layer was dried over anhydrous
MgSO4, filtered and concentrated to give aminocoumarin 9a (77%), red crystals,
C16H13NO2: C, 76.48; H, 5.21; N, 5.77. Found: C, 76.46; H, 5.27; N, 5.73.
(f) 6-Methyl-3H-pyrano[3,2-f]quinoline-3-one (5b). Yield 50%, white crystals, mp
198–200 °C (lit.50 mp 200 °C); 1H NMR (300 MHz, CDCl3) d 2.07 (s, 3H), 6.56 (d,
1H, J = 9.8 Hz), 7.58 (s, 1H), 7.61 (dd, 1H, J1 = 4.2 Hz, J2 = 8.5 Hz), 8.40 (d, 1H,
J = 9.8 Hz), 8.55 (dd, 1H, J1 = 1.6 Hz, J2 = 8.5 Hz), 9.01 (dd, 1H, J1 = 1.6 Hz, J2=4.2
Hz); 13C NMR (75.5 MHz, CDCl3) d 18.8, 111.2, 115.3, 120.4, 122.4, 124.1, 129.8,
138.2, 144.0, 145.0, 148.9, 153.6, 160.7.
mp 155–157 °C (CH2Cl2), IR (KBr): 3453, 3347, 1705, 1646 cmꢂ1 1H NMR
;
(300 MHz, CDCl3) d 1.76–1.94 (m, 4H), 2.53 (t, 2H, J = 5.2 Hz), 2.89 (t, 2H,
J = 5.2 Hz), 5.01 (br s, 2H), 6.33 (d, 1H, J = 9.5 Hz), 6.59 (s, 1H) 7.57 (d, 1H,
J = 9.5 Hz), 13C NMR (75.5 MHz, CDCl3) d 18.3, 22.6, 25.1, 28.9, 109.4, 114.7,
119.1, 120.3, 135.4, 141.4, 150.2, 151.9, 160.4; MS (ESI): 216 [M+H]+ꢀ; 238
[M+Na]+ꢀ; Anal. Calcd for C13H13NO2: C, 72.57; H, 6.09; N, 6.51. Found: C, 72.48;
H, 6.14; N, 6.57.
(g) 2H-Benzo[h]pyrano[3,2-f]quinoline-2-one (16). Yield 42%, light-yellow
crystals, mp 238–241 °C (lit.50 mp 243 °C); 1H NMR (300 MHz, CDCl3) d 6.65
(d, 1H, J = 9.8 Hz), 7.63 (dd, 1H, J1 = 4.4 Hz, J2 = 8.3 Hz), 7.80–7.92 (m, 2H), 8.42
(d, 1H, J = 9.8 Hz), 8.51 (dd, 1H, J1 = 1.6 Hz, J2 = 8.3 Hz), 8.64 (dd, 1H, J1 = 1.7 Hz,
J2 = 7.5 Hz), 9.02 (dd, 1H, J1 = 1.6 Hz, J2 = 4.4 Hz), 9.33 (dd, 1H, J1 = 1.6 Hz,
J2 = 7.5 Hz); 13C NMR (75.5 MHz, CDCl3) d 116.2, 120.0, 122.8, 123.4, 125.1,
129.4, 129.7, 130.2, 133.4, 139.1, 140.8, 142.4, 148.7, 148.9, 154.0, 161.9.
48. Kitamura, T.; Yamamoto, K.; Kotani, M.; Oyadama, J.; Jia, C.; Fujiwara, Y. Bull.
Chem. Soc. Jpn. 2003, 76, 1889.
(d) General procedure for the propargylation of 6-aminocoumarins. Propargyl
bromide (2) (96 mg, 0.06 ml, 0.7 mmol) and anhydrous K2CO3 (74 mg,
0.7 mmol) were added to
a solution of 6-aminocoumarin 9a (0.15 g,
0.7 mmol) in dry acetone (15 ml) and refluxed for 5 d. The resulting mixture
was filtered, while hot and rinsed with acetone. The filtrate was evaporated
and subjected to column chromatography [silica gel, hexane/EtOAc (5:1)] to
give, from the faster moving band [before unreacted starting amine (25%)], 6-
49. Nicolaides, D. N.; Gautam, D. R.; Litinas, K. E.; Hadjipavlou-Litina, D. J.;
Fylaktakidou, K. C. Eur. J. Med. Chem. 2004, 39, 323.
(prop-2-yn-1-ylamino)-7,8,9,10-tetrahydro-2H-benzo[h]chromen-2-one
(10a)
50. Dey, B. B.; Goswami, M. N. J. Chem. Soc. 1919, 115, 531.