Synthesis of some C-3,4,5-substituted 2,6-dimethyl-1,4-dihydropyridines (4-DHPs)

Article abstract of DOI:10.1080/00397910701357007

A series of C-3,4,5-substituted 2,6-dimethyl-1,4-dihydropyridines (1,4-DHPs) with pharmacological properties were prepared by a variation from the classical Hantzsch synthesis. The procedure involves treatment of the respective aldehyde with either ethyl-3-aminocrotonate or 3-aminocrotonitrile in anhydrous acetic acid at temperatures not exceeding 60°C, thus minimizing by-product formation. The structures of title compounds were elucidated by 1H NMR, 13C NMR, FTIR, and elemental analysis. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910701357007

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Synthesis of Some C‐3,4,5‐Substituted
2
,6‐Dimethyl‐1,4‐dihydropyridines (4‐DHPs)
a b c c
Patricio A. Navarrete‐Encina , Juan A. Squella , J. Carbajo , B. Conde
b
&
Luis J. Núñez‐Vergara
a
University of Chile, Faculty of Chemical and Pharmaceutical Sciences,
Advanced Organic Synthesis Laboratory , Santiago R.M., Chile
b
Faculty of Chemical and Pharmaceutical Sciences, Bioelectrochemistry
Laboratory , University of Chile , Santiago, Chile
c
Faculty of Experimental Sciences , Huelva, Spain
Published online: 22 Jun 2007.
To cite this article: Patricio A. Navarrete‐Encina , Juan A. Squella , J. Carbajo , B. Conde & Luis J.
Núñez‐Vergara (2007) Synthesis of Some C‐3,4,5‐Substituted 2,6‐Dimethyl‐1,4‐dihydropyridines (4‐DHPs),
Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry,
7:12, 2051-2060
3
To link to this article: http://dx.doi.org/10.1080/00397910701357007
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Synthetic Communications , 37: 2051–2060, 2007
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910701357007
Synthesis of Some C-3,4,5-Substituted
2
,6-Dimethyl-1,4-dihydropyridines
4-DHPs)
(
Patricio A. Navarrete-Encina
Faculty of Chemical and Pharmaceutical Sciences, Advanced Organic
Synthesis Laboratory, University of Chile, Santiago, Chile
Juan A. Squella
Faculty of Chemical and Pharmaceutical Sciences, Bioelectrochemistry
Laboratory, University of Chile, Santiago, Chile
J. Carbajo and B. Conde
Faculty of Experimental Sciences, Huelva, Spain
Luis J. N u´ n˜ ez-Vergara
Faculty of Chemical and Pharmaceutical Sciences, Bioelectrochemistry
Laboratory, University of Chile, Santiago, Chile
Abstract: A series of C-3,4,5-substituted 2,6-dimethyl-1,4-dihydropyridines (1,4-
DHPs) with pharmacological properties were prepared by a variation from the
classical Hantzsch synthesis. The procedure involves treatment of the respective
aldehyde with either ethyl-3-aminocrotonate or 3-aminocrotonitrile in anhydrous
acetic acid at temperatures not exceeding 608C, thus minimizing by-product
1
13
formation. The structures of title compounds were elucidated by H NMR,
NMR, FTIR, and elemental analysis.
C
Keywords: cyclization, 1,4-dihydropyridines, nitrogen heterocycles
Received in the USA November 9, 2006
Address correspondence to Patricio A. Navarrete-Encina, Faculty of Chemical and
Pharmaceutical Sciences, Advanced Organic Synthesis Laboratory, University of
Chile, Casilla 233, Santiago R.M., Chile. E-mail: pnavarre@uchile.cl
2
051

2
052
P. A. Navarrete-Encina et al.
INTRODUCTION
Dihydropyridine (DHP) calcium antagonists decrease vascular contractility
and arterial tone by modulating the activity of the L class of voltage-gated
[1]
calcium channels in a variety of tissues. Other additional effects such anti-
In
[2a,b]
oxidant activity in various experimental models have been reported.
line with this, our laboratory has recently reported the direct reactivity
between some commercial and newly synthesized 1,4-DHP derivatives with
[
3a–c]
free radicals.
,4-Dihydropyridines were first synthesized by Hantzsch
[4a,b]
1
and over
the years a great variety of 1,4-DHPs have been synthesized that have
different substitutions on C , C , C , C , and C positions of the DHP
2
3
4
5
6
[
5a,b,c]
ring.
. Because the pharmacological prototype of 1,4-dihydropyridine,
nifedipine, does not have optimum pharmacokinetic and pharmacodynamic
characteristics, several attempts have been made to synthesize other
[6]
drugs of this class with additional properties, such as antioxidants and
[
7a,b]
releasers of nitric oxide.
The structure–activity relationship of the
dihydropyridines indicated that most of the desired properties rely on
the structural characteristics of the substituent at 4-position of the
dihydropyridine nucleus, especially if that substituent is an aromatic
phenyl ring. Introduction of electron-donating substituents and electron-
withdrawing substituents produced relevant changes in pharmacological
[
8a]
effects.
Particularly for optimal activity of 1,4-dihydropyridines as antagonists,
some moieties are essential and can be summarized as (a) the presence
of the intact 1,4-dihydropyridine ring, (b) the secondary nitrogen in the
heterocycle, and (c) a space-filling substituent in para-position of the
dihydropyridine ring; also (d) the presence of ester groups at 3-
and 5-positions and methyl groups in 2- and 6-positions on the dihydro-
pyridine ring are relevant to conserve the antagonistic effects of the
[
9]
derivatives.
In this article, the synthesis of some 5-nitrofuryl DHPs derivatives was
also included. The idea behind this structural variation was based on a
previous knowledge that some commercial calcium channel blockers and
other 1,4-dihydropyridines having a 5-nitrofuryl substituent displayed signifi-
[10a–d]
cant inhibitory effects on epimastigotes cultures of Trypanosoma cruzi.
Considering that there is a need for new 1,4-DHPs, we have synthesized some
C-3,4,5-substituted 2,6-dimethyl-1,4-DHPs that have the presence of at least
one hydroxyl group in the aromatic ring at 4-position as a common structural
characteristic, maintaining ethoxycarbonyl groups at positions 3 and 5, and
others having a 5-nitrofuryl substituent at 4-position but different substituents
at positions 3 and 5 of the DHP.
We failed in our attempts to synthesize the compounds using the conven-
tional classical Hantszch’s dihydropyridine synthesis (with the exception of
compound IX) or obtained poor yields.

C-3,4,5-Substituted 2,6-Dimethyl-1,4-dihydropyridines
RESULTS AND DISCUSSION
2053
Synthesis of the Derivatives
The 1,4-dihydropyridine compounds described in this work were
synthesized by a procedure involving mixing ethylaminocrotonate or amino-
crotonitrile and the respective aldehyde in anhydrous acetic acid. Although
the Hantzsch synthesis was first published well more then a century ago, the
dihydropyridines we synthesized cannot be directly obtained by
the Hantzsch method, and all of them are new compounds (with the
exception of compound IX, which was previously obtained using
[
11]
the classical Hantzsch synthesis).
listed in Table 1 in accordance with Fig. 1. These dihydropyridines deriva-
The synthesized compounds are
1
13
tives were identified and characterized by H NMR and C NMR spec-
troscopy using a 300-MHz spectrometer (Bruker, WM 300), infrared
spectroscopy (FT-IR Paragon spectrometer, 100PC), and elemental
analysis (Perkin Elmer, 240 B).
It was not possible to synthesize the 2-hydroxyphenyl derivative because
of poor yields and by-product formation using either the classical Hantszch
method or the variation just described. We are attempting an indirect
synthetic route leading to the compound. Yields of 2,4-dihydroxyphenyl
and 2,5-dihydroxyphenyl derivatives were also relatively poor (25% and
2
4% respectively). These results may be attributed to adduct formation in
the case of the reaction of 2-hydroxyaldehydes and 3-aminocrotonitrile, as
was previously reported for the reaction of 3-aminocrotononitrile with salicy-
[
12]
laldehyde. In that work, Hafiz describes the formation of a 2:2 adduct as the
main reaction product, instead of the DHP derivative, as a result of a further
reaction of the aldehyde with the DHP formed. Attempts to isolate the adduct
failed.
Table 1. Synthesized compounds
1
R
2
R
Compound
R
I
3-Hydroxyphenyl
4-Hydroxyphenyl
-CO
-CO
-CO
2
2
2
Et
Et
Et
-CO
-CO
-CO
2
2
2
Et
Et
Et
II
III
IV
V
2,4-Dihydroxyphenyl
3,4-Dihydroxyphenyl
2,5-Dihydroxyphenyl
3,5-Dihydroxyphenyl
4-Hydroxy-3-Methoxyphenyl
3-Hydroxy-4-Methoxyphenyl
2-Nitrofuro-5-yl
-CO Et
2
-CO Et
2
-CO
-CO
2
Et
Et
-CO
-CO
2
Et
Et
VI
VII
VIII
IX
X
2
2
-CO Et
2
-CO Et
2
-CO
-CO
-CN
-CN
2
Et
Et
-CO
-CO
-CN
2
Et
Et
2
2
2-Nitrofuro-5-yl
XI
2-Nitrofuro-5-yl
-CO Et
2

2
054
P. A. Navarrete-Encina et al.
Figure 1. General chemical structure of the synthesized compounds.
A proposal for a general mechanism in the case of the 5-nitrofuryl-
DHPs is described in Scheme 1; however, we did not isolate any of the
intermediates. In this mechanism, the formation of compound 6 is
assumed to be formed via initial condensation of the aldehyde 1 with
one molecule of enamine 2a to yield the unstable ylidene derivative
[
13]
3
.
Reaction of the ylidene with another molecule of enamine 2b
yields the diamine 4, which cyclizes into 5. Loss of NH from 5 yields
3
the final product 6.
We have also concluded that the acid-catalyzed condensation reaction of
one molecule of aldehyde and two molecules of enamines is a facile and
efficient synthetic route to prepare these kinds, of 2,6-dimethyl-1,4-dihydro-
pyridine derivatives.
Scheme 1. Proposed reaction pathway for the synthesis of the C-3,4,5-1,4-DHP
1
derivatives. R, R , and R are in accordance with Table 1.
2

C-3,4,5-Substituted 2,6-Dimethyl-1,4-dihydropyridines
EXPERIMENTAL
2055
General Synthetic Procedure for Compounds I–X
A mixture of the respective aldehyde (0.016 mol) and ethylaminocrotonate
4.2 mL, 0.033 mol) is heated in an Erlenmeyer flask in a water bath until
complete dissolution of the aldehyde. After addition of anhydrous acetic acid
15 mL), the mixture is further heated for 1 h. It is important not to exceed
08C, thus minimizing by-product formation. The orange, viscous solution is
filtered off and left until room temperature is attained. Water is carefully added
one drop at a time) until cloudiness is obtained; this is necessary to further pre-
(
(
6
(
cipitate the DHP. The solution is warmed again to obtain a clear solution and left
overnight, thus permitting the slow crystallization of the derivative.
0 0
-Cyano-5-ethoxycarbonyl-4-(2 -furyl-5 -nitro)-2,6-dimethyl-1,4-
dihydropyridine (XI)
3
Ethyl 3-aminocrotonate (A) (0.65 g, 5 mmol), 3-aminocrotononitrile (B)
(0.41 g, 5 mmol), and 5-nitro-2-furaldehyde (C) (0.63 g, 5 mmol) were separ-
ately dissolved in glacial acetic (10 mL). Solutions A and B were slowly
added to solution C at 458C, with vigorous stirring. The resulting mixture
was gently heated for 15 min. The product was precipitated from the
reaction mixture by careful addition of water. The precipitate was filtered
off and washed with ethyl ether. The crude product was purified twice by
column chromatography (adsorbent: silica gel; eluting solvents: EtOAc–
petroleum ether 1:3; dichloromethane).
Physical Characterization
2,6-Dimethyl-3,5-dietoxycarbonyl-4-(3-dihydroxyphenyl)-1,4-
dihydropyridine (I)
Yield: 85%. Mp: 188–1918C. IR (KBr): nmax 3351.1, 1649.8, 1594.5, 1473.3,
1
367.6, 1216.8, 1127.6, 1018.4. H NMR (300 MHz, acetone-d6): 1.2
1
(
t, J ¼ 7.0, 6H, -CH ); 2.3 (s, 6H, -CH ); 2.9 (s, 1H, C-H); 4.1 (q, J ¼ 7.0,
3
3
1
3
4
H, -CH ); 5.0 (s, 1H, -OH); 6.9 (m, 4H, aromatic); 7.8 (s, 1H, N-H).
2
C
NMR (75 MHz, acetone-d6): ppm 13.8(2); 17.9(2); 29.0; 38.6; 58.9(2);
03.3(2); 114.4(2); 115.0; 119.1; 130.5; 144.3; 165.3; 205.5(2). Anal. calcd.
for C H NO : C, 66.07; H, 6.71; N, 4.06. Found: C, 65.87; H, 6.69; N, 4.06.
1
1
9
23
5
2,6-Dimethyl-3,5-dietoxycarbonyl-4-(4-hydroxyphenyl)-1,4-
dihydropyridine (II)
Yield: 70%. Mp: 232–2358C. IR (KBr): n
1
3354.1, 1655.8, 1591.7, 1478.5,
367.1, 1220.3, 1122.4, 1019.7. H NMR (300 MHz, acetone-d6): 1.2
max
1

2
056
P. A. Navarrete-Encina et al.
(
t, J ¼ 7.0, 6H, -CH ); 2.3 (s, 6H, -CH ); 2.9 (s, 1H, C-H); 4.1 (q, J ¼ 7.0, 4H,
3
3
-
aromatic); 7.8 (s, 1H, N-H). C NMR (75 MHz, acetone-d6): ppm 13.6(2);
CH ); 5.0 (s, 1H, -OH); 6.6 (d, J ¼ 8.0, 2H, aromatic); 6.8 (d, J ¼ 8.0, 2H,
2
1
3
18.3(2); 30.0; 37.9; 59.3(2); 107.5(2); 113.2(2); 118.0; 119.3; 132.7; 141.2;
161.4(2); 207.3. Anal. calcd. for C H NO : C, 66.07; H, 6.71; N, 4.06.
Found: C, 66.16; H, 6.68; N, 4.08.
1
9
23
5
2,6-Dimethyl-3,5-dietoxycarbonyl-4-(2,4-dihydroxyphenyl)-1,4-
dihydropyridine (III)
Yield: 25%. Mp: 190.0–193.08C. IR (KBr): nmax 3334.3, 1724.6, 1699.4,
1
627.1, 1627.1, 1560.1, 1442.4, 1384.6, 1241.0, 1096.6, 1030.7, 839.1,
1
8
00.3. H NMR (300 MHz, acetone-d6): d 1.4 (t, J ¼ 7.0, 6H, -CH ); 2.6
3
(
s, 6H, -CH ); 2.7 (s, 1H, C-H); 4.9 (q, J ¼ 7.0, 4H, -CH ); 6.7 (s, 1H,
3
2
3
6
1
1
3
-aromatic); 6.8 (d, J ¼ 6.4, 1H, 5-aromatic); 8.4 (d, J ¼ 6.4, 1H,
1
3
-aromatic); 9.4 (s, 1H, N-H). C NMR (75 MHz, acetone-d6): ppm
3.9(2); 18.8(2), 23.3; 29.4; 61.5(2); 96.0(2); 102.2; 112.2; 113.3; 126.6(2);
61.7; 197.5; 204.8(2). Anal. calcd. for C O NH : C, 63.15; H, 6.41; N,
1
9
6
23
.87. Found: C, 63.39; H, 6.38; N, 3.89.
2,6-Dimethyl-3,5-dietoxycarbonyl-4-(3,4-dihydroxyphenyl)-1,4-
dihydropyridine (IV)
Yield: 62%. Mp: 195.0–197.08C. IR (KBr): nmax 3411.3, 1666.4, 1470.9,
1
370.8, 1274.6, 1218.8, 1123.0, 1020.7, 781.0. H NMR (300 MHz,
1
acetone-d6): d 1.2 (t, J ¼ 7.0, 6H, -CH ); 2.3 (s, 6H, -CH ); 3.0 (s, 1H,
3
3
C-H); 4.0 (q, J ¼ 7.0, 4H, -CH ); 4.9 (s, 2H, -OH); 6.6 (s, 1H, 2-aromatic);
2
6
.8 (d, J ¼ 7.0, 1H, 6-aromatic); 7.6 (d, J ¼ 7.0, 1H, 5-aromatic); 7.8
1
s, 1H, N-H). C NMR (75 MHz, acetone d6): ppm 13.8(2); 17.9(2); 29.0;
3
(
3
2
6
8.6; 58.9(2); 103.3(2); 114.4; 115.1; 119.1; 140.5; 144.3(2); 165.3;
05.5(2). Anal. calcd. for C O NH : C, 63.15, H, 6.41; N, 3.87. Found: C,
1
9
6
23
2.95; H, 6.40; N, 3.89.
2,6-Dimethyl-3,5-dietoxycarbonyl-4-(2,5-dihydroxyphenyl)-1,4-
dihydropyridine (V)
Yield: 24%. Mp: 2458C. IR (KBr): nmax 3256.7, 1726.7, 1687.1, 1555.1,
1
464.1, 1399.7, 1231.3, 1102.2, 1028, 819.5. H NMR (300 MHz, acetone-
1
d6): d 1.3 (t, J ¼ 7.0, 6H, -CH ); 2.5 (s, 6H, -CH ); 2.6 (s, 1H, C-H); 4.3
3
3
(
q, J ¼ 7.0, 4H, -CH ); 7.0 (d, J ¼ 5.8, 1H, 4-aromatic); 7.1 (s, 2H, -OH);
2
7
1
.1 (s, 1H, 6-aromatic); 7.8 (d, J ¼ 5.8, 1H, 3-aromatic); 8.7 (s, 1H, N-H).
C NMR (75 MHz, acetone-d6): ppm 13.6(2); 18.7(2); 23.1; 29.1; 61.7(2);
5.7(2); 109.7; 117.4; 120.5; 149.2(2); 154.1; 159.9; 205.2(2). Anal. calcd.
3
9
for C O NH : C, 63.15; H, 6.41; N, 3.87. Found: C, 63.39; H, 6.40; N, 3.86.
9
1
6
23

C-3,4,5-Substituted 2,6-Dimethyl-1,4-dihydropyridines
2057
2,6-Dimethyl-3,5-dietoxycarbonyl-4-(3,5-dihydroxyphenyl)-1,4-
dihydropyridine (VI)
Yield: 60%. Mp: 245–2478C. IR (KBr): nmax 3403.7, 2979.6, 1672.2, 1599.0,
1
473.1, 1373.3, 1221.2, 1156.5, 1004.2, 844.6, 800.3, 619.5. H NMR (300
1
MHz, acetone-d6): d 1.1 (t, J ¼ 7.0, 6H, -CH ); 2.2 (s, 6H, -CH ); 2.9
3
3
(
s, 1H, C-H); 3.9 (m, 4H, -CH ); 4.8 (s, 2H, -OH); 6.2 (s, 1H, 4-aromatic);
2
1
.7 (s, 2H, 2,6-aromatic); 7.8 (s, 1H, N-H). C NMR (75 MHz, acetone-
3
7
d6): ppm 13.8(2); 17.9(2); 29.0; 39.1; 59.0(2); 100.2(2); 102.8; 106.2;
1
44.6; 150.4(2); 158.0, 167.2; 205.4(2). Anal. calcd. for C O NH : C,
19 6 23
6
3.15; H, 6.41; N, 3.87. Found: C, 62.90; H, 6.43; N, 3.89.
2
1
,6-Dimethyl-3,5-dietoxycarbonyl-4-(4-hydroxy-3-methoxyphenyl)-
,4-dihydropyridine (VII)
Yield: 80%. Mp: 161–1638C. IR (KBr): n
1
3350.5, 2982.8, 1680.9, 1653.2,
514.4, 1490.1, 1217.8, 1122.5. H NMR (300 MHz, acetone-d6): d 1.2
max
1
(
t, J ¼ 7.0, 6H, -CH ); 2.3 (s, 6H, -CH ); 3.7 (s, 3H, -OCH ); 4.1
3
3
3
(
q, J ¼ 7.0, 4H, -CH ); 5.0 (s, 1H, -CH); 7.0 (m, 4H, aromatic); 6.9 (s, 1H,
2
1
N-H); 7.8 (s, 1H, -OH); C NMR (75 MHz, acetone-d6): ppm 14.2(2);
3
1
9.6(2); 41.5; 55.9; 60.1(2); 96.8(2); 111.8; 117.6; 121.5; 133.2; 144.9;
48.86(2); 149.1; 166.1(2). Anal. calcd. for C H NO : C; 66.83; H; 7.01;
N; 3.89. Found: C, 66.78; H, 6.98; N, 3.88.
1
2
0
25
5
2
1
,6-Dimethyl-3,5-dietoxycarbonyl-4-(3-hydroxy-4-methoxyphenyl)-
,4-dihydropyridine (VIII)
Yield: 62%. Mp: 166–1688C. IR (KBr): n
1
3316.2, 1669.1, 1483.3, 1372.0,
270.6, 1114.9, 1016.4, 765.4. H NMR (300 MHz, acetone-d6): d 1.2
max
1
(
t, J ¼ 7.0, 6H, -CH ); 2.7 (s, 6H, -CH ); 3.7 (s, 3H, -OCH ); 4.1
3
3
3
(
q, J ¼ 7.0, 4H, -CH ); 4.9 (s, 1H, -CH); 6.3 (s, 1H, N-H); 7.1 (m, 3H,
2
1
aromatic); 8.1 (s, 1H, -OH). C NMR (75 MHz, acetone-d6): ppm
3
1
1
4.23(2); 19.60(2); 41.05; 58.05; 60.13(2); 98.82(2); 114.03; 115.32;
19.25; 133.52; 146.17; 149.10(2); 150.36; 166.13(2). Anal. calcd. for
C H NO : C, 66.83; H, 7.01; N, 3.89. Found: C, 66.95; H, 7.03; N, 3.90.
2
0
25
5
0 0
,6-Dimethyl-3,5- diethoxycarbonyl-4-(5 -nitro-2 -furyl)-1,4-
dihydropyridine (IX)
2
Yield: 60%. Mp: 184.28C. IR (KBr): n
3346.7, 1704.3, 1656.0, 1517,
487.9, 1400.0, 1355.0, 1211.9, 1114.4. H NMR (300 MHz, CDCl ): d
max
1
1
1
5
7
1
3
.28 (t, J ¼ 7.1, 6H, -CH ); 2.36 (s, 6H, -CH ); 4.15 (q, J ¼ 7.1, 2H, -CH );
3
3
2
.27 (s, 1H, -CH); 6.19 (s, 1H, N-H); 6.26 [d, J ¼ 3.4, 1H, -CH (3-furyl)],
1
3
.21 [d, J ¼ 3.4, 1H, -CH (4-furyl)]. C NMR (75 MHz, CDCl ): ppm
3
66.8 (2); 162.7 (2); 146.4 (2); 113.2; 108.9, 99.0 (2); 60.2 (2); 34.6; 19.6

2
058
P. A. Navarrete-Encina et al.
(
C, 55.85; H, 5.54; N, 7.72.
2); 14.3 (2). Anal. calcd. for C H N O : C, 56.04; H, 5.53; N, 7.69. Found:
1
7
20
2
7
0
0
3
,5-Dicyano-2,6-dimethyl-4-(5 -nitro2 -furyl)-1,4-dihydropyridine (X)
Yield: 63%. Mp: 2258C. IR (KBr): n
1
3369.2, 2205.9, 1665.8, 1536.3,
505.1, 1393.1, 1358.8. H NMR (300 MHz, DMSO-d ): d 2.07 (s, 6 H,
max
1
6
-
CH ); 4.92 (s, 1H, -CH); 6.82 [d, J ¼ 3.8, 1H, -CH (3-furyl)], 7.70 [d,
3
1
3
J ¼ 3.8, 1H, -CH (4-furyl)]; 9.81 (s, 1H, N-H). C NMR (75 MHz,
DMSO-d ): ppm 159.7 (2); 158.0 (2); 121.8 (2); 114.9; 111.9; 73.8 (2);
6
33.9; 20.8 (2). Anal. calcd. for C H N O : C; 57.78; H; 3.73; N; 20.73.
13 10 4 3
Found: C; 57.75; H; 3.73; N; 20.65.
-Cyano-5-ethoxycarbonyl-2,6-dimethyl-4-(5 -nitro-2 -furyl)-1,4-
dihydropyridine (XI)
0
0
3
Yield: 80%. Mp: 161.98C. IR (KBr): nmax 3317.9, 2199.4, 1664.3, 1638.5,
1
527.1, 1493.1, 1383.0, 1355.5, 1257.0, 1115.7. H NMR (300 MHz,
1
CDCl ): d 1.29 (t, J ¼ 7.1, 3H, -CH ); 2.18 [s, 3H, -CH (2)]; 2.38 [s, 3H,
3
3
3
-
CH (6)]; 4.12 (q, J ¼ 7.1, 2H, -CH ); 4.90 (s, 1H, -CH); 6.04 (s, 1H,
3
2
N-H); 6.38 [d, J ¼ 3.7, 1H, -CH (3-furyl)], 7.24 [d, J ¼ 3.7, 1H, -CH (4-
1
furyl)]. C NMR (75 MHz, CDCl ): ppm 166.2; 160.0 (2); 147.6; 146.3;
3
3
118.6; 113.0; 109.5; 97.6; 81.8; 60.5; 35.9; 19.7; 18.5; 14.2. Anal. calcd. for
C H N O : C, 56.78; H, 4.76; N, 13.24. Found: C, 56.56; H, 4.77; N; 13.19.
1
5 15 3 5
ACKNOWLEDGEMENTS
This article was supported by a grant from FONDECYT Project No. 1050761.
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