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Original article
9 (
2_suppl
); S1740-S1746
doi:
10.1016/j.arabjc.2012.04.046

Solvent free synthesis of 3,4-dihydropyrimidine-2-(1H)-ones/thiones catalyzed by N,O-bis(trimethylsilyl)acetamide and dicyclohexyl carbodimide

, ,
a Department of Organic Chemistry, Foods, Drugs & Water, Andhra University, Visakhapatnam 530003, India
b Department of Science and Humanities, MVGR College of Engineering, Vijayanagaram 535005, India

⁎Corresponding authors: Tel.: +91 9032837383; fax: +91 891 2713813 (Y.L.N. Murthy). abdulrazzack1@gmail.com (Abdul Rajack)

Received: , Accepted: ,
© The Author(s) 2012
Disclaimer:
This article was originally published by Elsevier and was migrated to Scientific Scholar after the change of Publisher.

Peer review under responsibility of King Saud University.

Abstract

We report herein, the usage of N,O-bis(trimethylsilyl)acetamide (BSA) and dicyclohexyl carbodimide (DCC) as two new catalysts for three component condensation of an aldehyde, ethyl acetoacetate and urea/thiourea under solvent free conditions at 100 °C to afford the corresponding 3,4-dihydropyrimidine-2-(1H)-ones/thiones (DHPMs) in good to excellent yields. A comparative study of these two catalysts was made and presented.

Keywords

N,O-Bis(trimethylsilyl)acetamide
Dicyclohexyl carbodimide
Solvent free
3,4-Dihydropyrimidinones
3,4-Dihydropyrimidithiones
1

1 Introduction

In the recent decades, the developments of multi component condensations (Ugi et al., 1994; Domling, 2006) (MCCs) are of increasing importance in organic and medicinal chemistry for modern drug discovery. It was soon established that DHPMs exhibit similar therapeutic and pharmacological profile to 1,4 dihydropyridines (DHPs) calcium channel modulator of the nefidine (Domling, 1998; Plunlett and Ellman, 1997; Schreiber, 2000). From the past two decades synthesis of DHPMs and their derivatives being a hot area of research due to their wide spectrum of biological activities (Bryzgalov et al., 2006; Holla et al., 2004; Zorkun et al., 2006; Kappe, 1993, 1998, 2000a,b; Chitra et al., 2010; Atwal et al., 1991; Rovnyak et al., 1992), including antibacterial, antiviral, antitumor, anti-inflammatory, antiarrhythmic activity, antifungal activities, and antihypertensive as well as the most potent Ca2+ channel blockers (Rovnyak et al., 1995; Aswal et al., 1990). Recently, inhibitors of the fatty acid transporter FATP4 (Christopher et al., 2006), one of the DHPMs derivative monastrol has emerged as a new chemical tool for investigating human mitotic kinesin Eg5 (Emmanuel et al., 2007) motor protein inhibitor for the development of anticancer drugs. Furthermore, the marine alkaloids attributed to the dihydro pyrimidinones moiety in the structure isolated from natural marine sources such as crambine, batzelladine B (potent HIVgp-120CD4 inhibitors) (Rama Rao et al., 1995).

The classical Biginelli reaction (Biginelli et al., 1888); Kolosov et al., 2009) is the MCCs of aldehyde, ethyl acetoacetate and urea/thiourea refluxed at100 °C in ethanol, in the presence of acetic acid for 8 h. Several synthetic methodologies such as solvent free (Weike, 2005; Bahrami et al., 2009; Besoluk et al., 2008; Jing et al., 2009), ultrasounds (Yadav et al., 2001), ionic liquids (Sushilkumar et al., 2004; Jiajian, 2001), microwave synthesis (Kalyan Kumar, 2011; Kidwai et al., 2002; Khabazzadeh et al., 2008), Green approach synthesis (Ranu et al., 2002; Subhas et al., 2003; Rafiee and Jafari, 2006; Zheng-Jun et al., 2009; Mridula et al., 2010), phase-transfer catalysis (Bahar, 2009), baker's yeast (Atu and Ram, 2007), Brønsted acids (Yang et al., 2007; Shutalev and Sivova, 1998; Renwei, 2006), Brønsted bases (Zhi-Liang et al., 2010), Lewis acids (Ramalingan et al., 2008; Paraskar et al., 2003; Kumar et al., 2001; Anil et al., 2007; Ma et al., 2000; Brindaban et al., 2000; Zhua, 2004; Surya et al., 2005; Hamid Reza et al., 2009), were developed to synthesize the 3,4 dihydro pyrimidinones/thiones. Out of all these methodologies to the best of our knowledge, there are two reports employing (PPh3) as a Lewis base (Debache et al., 2008). Herein, we report two new catalysts viz. (a) BSA (N,O-bis-(trimethylsilyl)acetamide) (b) DCC (dicyclohexyl carbodimide) for the synthesis of DHPMs under solvent free conditions at 100 °C, in an efficient way, good to excellent yields are obtained (Scheme 1).

Synthesis of 3,4-dihydropyrimidinones/thiones catalyzed by BSA or DCC under solvent free conditions.
Scheme 1
Synthesis of 3,4-dihydropyrimidinones/thiones catalyzed by BSA or DCC under solvent free conditions.

2

2 Results and discussions

BSA and DCC are the two good moisture absorbents. These two reagents were employed individually as a catalyst in the Biginelli reaction to produce DHPMs from aromatic aldehyde, ethyl acetoacetate and urea (4a-1 to 4j-1 and 4a-3 to 4j-3) or thiourea (4a-2 to 4j-2 and 4a-4 to 4j-4). In an initial endower the reaction was performed with 10 mole % of catalyst at RT in different solvents viz. ethanol, methanol, tetrahydrofuran, t-butanol, dioxan, acetonitrile and under solvent free conditions. Even after 24 h the reaction was not moved at RT, when the reaction temperature was raised to 100 °C after 24 h only 20–30% of the product was obtained under solvent free and catalyst free conditions. In the presence of BSA or DCC catalyst yielded better results with low reaction times under solvent free conditions. To optimize the amount of the catalyst we have carried out the reaction with various mole % of the catalysts. However there is no recognizable change in either % of yield or the reaction time by the increased amounts in catalysts over 10 mol % of both BSA and DCC (Table 1). To elaborate the catalysts efficiency we have examined the same reaction with other Brønsted bases, Lewis bases and Lewis acids under solvent free conditions the results are recorded in (Table 2). To define the scope and limitations, the efficiency of the catalysts (BSA and DCC) was examined with several aldehydes, ethyl acetoacetate and urea/thiourea. Between these two catalysts, the best results are produced with BSA. The final product (DHPMs) yields affected by the substitutions in the benzene ring, electron withdrawing groups like nitro groups leads relatively higher yields than electron donating groups like alkyl, alkoxy and hydroxy groups (Table 3).

Table 1 Optimization of catalysts (BSA or DCC) under solvent free conditions.
Entry Solvent Mole % of BSA/DCC Time (h) Yield (%)
X = O X = S
1 EtOH 10 20 50a 47b 46a 42b
2 MeOH 10 20 47a 45b 35a 39b
3 THF 10 18 20a 27b 13a 17b
4 Dioxan 10 24 20a 15b 16a 13b
5 CH3CN 10 24 30a 33b 32a 32b
6 Solvent free 05 3–4 30a 15b 43a 12b
7 Solvent free 10 3–4 80a 71b 57a 54b
8 Solvent free 15 3–4 82a 68b 55a 51b
9 Solvent free 20 3–4 81a 70b 56a 55b
a Isolated yields of DHPMs with BSA.
b Isolated yields of DHPMs with DCC.
Table 2 Comparison of BSA/DCC catalyzed synthesis of DHPMs with other basic and acidic catalysts.
Entry Catalyst Time (h) Yield (%)
1 t-BuOK 10–12 57a 55b
2 BSA 1.2–4 80a 57b
3 DCC 1.3–4 71a 54b
4 PPh3 10–12 30a 29b
5 BF3et2O 6–8 43a 40b
6 AlCl3 8–10 40a 40b
7 Catalyst free 15–20 30a 20b
a Isolated yields of dihydro pyrimidinones.
b Isolated yields of dihydro pyrimidithiones.
Table 3 BSA or DCC catalyzed synthesis of 3, 4-dihydropyrimidinones/thiones under solvent free conditions.
Entry R-CHO Catalyst x Product Time (min) Yielda (%) Mp found Mp reference
1 BSA O 4a-1 200 80 182–183b
S 4a-2 260 54 180–181c 184–186 (Besoluk et al., 2008)
O 4a-3 230 71 183–184(Besoluk et al., 2008)
S 4a-4 260 57
2 BSA O 4b-1 140 85
S 4b-2 180 72 172–173b 175–177 (Bahrami et al., 2009)
DCC O 4b-3 170 83 210–212c 212–214 Bahar, 2009
S 4b-4 130 75
3 BSA O 4c-1 140 78
S 4c-2 170 66 201–202b 202–20318a
DCC O 4c-3 150 72 150–152c 152–153 (Khabazzadeh et al., 2008)
S 4c-4 180 61
4 BSA O 4d-1 170 90
S 4d-2 200 81 208–210b 210–212 (Debache et al., 2008)
DCC O 4d-3 170 81 182–183c 184–185 (Debache et al., 2008)
S 4d-4 200 80
5 BSA O 4e-1 100 87
S 4e-2 80 85 210–212b 214–215 (Besoluk et al., 2008)
DCC O 4e-3 130 86 218–220c 219–221 (Besoluk et al., 2008)
S 4e-4 120 74
6 BSA O 4f-1 180 88
S 4f-2 220 79 200–202b 204–205 (Besoluk et al., 2008)
DCC O 4f-3 190 89 161–162c 163–164 (Besoluk et al., 2008)
S 4f-4 240 75
7 BSA O 4g-1 140 90
S 4g-2 110 75 229–230b 230–232 (Besoluk et al., 2008)
DCC O 4g-3 90 85 204–205c 206–207 (Besoluk et al., 2008)
S 4g-4 110 73
8 BSA O 4h-1 260 85
S 4h-2 220 87 234–235b 237–238 (Slimi et al., 2016)
DCC O 4h-3 200 84 192–194c 193–195 (Mridula et al., 2010)
S 4h-4 150 76
9 BSA O 4i-1 240 85
S 4i-2 260 75 180–181b 180–18218b
DCC O 4i-3 290 78 200–201c 202–204 (Subhas et al., 2003)
S 4i-4 300 72
10 BSA O 4j-1 230 90
S 4j-2 260 78 200–202b 202–204 (Mridula et al., 2010)
DCC O 4j-3 230 82 200–201c 200–205 (Mridula et al., 2010)
S 4j-4 240 75
a Isolated yields,
b Melting points of 3,4-dihydropyrimidinone,
c Melting points of 3,4-dihydropyrimidithione.

The reaction may proceed via acylimine intermediate, formed by the reaction of the aldehyde and urea/thiourea. Subsequent addition of β-ketoester enolate to the acylimine, followed by cyclization and dehydration by the catalysts BSA or DCC, afforded the corresponding 3, 4-dihydropyrimidinones/thiones. Schemes 2 and 3 were the deniable mechanisms in the synthesis Biginelli 3,4-dihydropyrimidinones/thiones. More recently similar kind of mechanism was explained by Debache et al. (2008), Slimi et al. (2016), Folkers et al. (1932), Mamaev and Dubovenko (1970) and Valverde et al. (2001).

Plausible mechanism for the synthesis of 3,4-dihydropyrimidinones/thiones with DCC.
Scheme 2
Plausible mechanism for the synthesis of 3,4-dihydropyrimidinones/thiones with DCC.
Plausible mechanism for the synthesis of 3,4-dihydropyrimidinones/thiones with BSA.
Scheme 3
Plausible mechanism for the synthesis of 3,4-dihydropyrimidinones/thiones with BSA.

3

3 Conclusion

To sum up, we have developed novel methodologies for the synthesis of DHPMs carried out by BSA/DCC under solvent free conditions, excellent catalysts for one pot synthesis of dihydropyrimidinones/thiones under solvent free conditions, short reaction time, high yields of products, simple work up procedures and easy isolation making it an important supplement to the existing methods. Further, we are studying the scope of these catalysts to the other organic multicomponent reactions.

4

4 Experimental

4.1

4.1 General procedure for synthesis of 3,4-dihydropyrimidinones/thiones under solvent free conditions

Aromatic aldehyde (0.01 moles), ethyl acetoacetate (0.012 moles) and urea/thiourea (0.01 moles) were stirred at 100 °C in the presence of BSA/DCC (10 mol %) for 110–300 min, the reaction was monitored by thin layer chromatography (TLC) [6:4 hexane–ethyl acetate]. After the completion of the reaction the reaction mixture was cooled and washed with ice cooled water, the separated solid was filtered and dried in vacuum, the solid product passed over a column of silica gel (60–100 mesh), finally recrystallized from alcohol to afford the desired product in pure form. Melting points were measured on Polmon melting point apparatus Mp 96. IR spectra were recorded on a Shimadzu IR Affinity-1. 1H and 13C NMR spectra were recorded on a Bruker DRX 200 spectrometer and 50 MHz, respectively. NMR spectra were obtained on solutions in CDCl3 and DMSO-d6. Mass spectra were recorded on water XEVO QTof mass spectrometer.

4.2

4.2 4-(3-Hydroxy-phenyl)-6-methyl-2-thioxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylicacid ethyl ester (4a-2)

Mp 182–183 °C; IR (KBr): 3423, 3095, 2920, 2823, 1719, 1658, 1517 cm−1; 1H NMR (200 MHz, DMSO-d6): δ 1.16 (t, J = 7.2 Hz, 3H OCH2CH3), 2.21 (s, 3H, CH3), 4.02 (q, J = 7.2 Hz, 2H, OCH2CH3), 5.17 (d, J = 3.0 Hz, 1H, CH-Ar), 6.81 (s, 1H, Ar-H), 6.90 (d, J = 8.2 Hz, 1H, Ar-H), 7.11 (d, J = 7.2 Hz, 1H, Ar-H), 7.25–7.35 (m, 1H, Ar-H) 7.28 (d, J = 8.2 Hz), 7.24 (br s, N–H), 8.90 (br s, N–H), 9.15 (s, 1H, OH); 13C NMR (50 MHz, DMSO-d6): δ 174.5, 165.2, 157.2, 144.8, 144, 129, 117.3, 114.9, 113.6, 102.3, 59.5, 54.7, 17.5, 13.9; EIMS: m/z [M+1]+: 292.

4.3

4.3 4-(3Hydroxy-phenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylicacid ethyl ester (4a-1)

Mp 180–181 °C; IR (KBr): 3512, 3352, 3244, 3119, 2980, 1718, 1678, 1600, 1460, 1229, 1094, 872, 779 cm−1; 1H NMR (200 MHz, DMSO-d6): δ 1.12 (t, 3H, J = 7.2 Hz, CH3), 2.24 (s, 3H, CH3), 3.99 (q, 2H, J = 7.2 Hz, OCH2–CH3), 5.07 (d, 1H, J = 3.0 Hz, CH-Ar), 6.61–6.68 (m, 3H, Ar-H), 7.09 (t, 1H, J = 8.0 Hz, Ar-H), 7.68 (s, 1H, NH), 9.15 (s, 1H, OH), 9.35 (s, 1H, NH); 13C NMR (50 MHz, DMSO-d6): δ 165.8, 157.8, 152.7, 148.5, 146.7, 129.7, 117.3, 114.6, 113.5, 99.9, 59.7, 54.3, 18.2,14.6; EIMS m/z [M+1]+: 277.11.

4.4

4.4 4-(3,4-Dimethoxy-phenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylicacid ethyl ester (4b-1)

Mp 171–173 °C; IR (KBr): 3350, 3220, 3190, 2984, 1668, 1650, 1620 cm−1; 1H NMR (200 MHz, DMSO-d6): δ 1.15(t, J = 8.2 Hz, 3H OCH2CH3), 2.14(s, 3H, CH3), 3.86 (s, 6H, 2×OCH3), 4.01(q, J = 8.2 Hz, 2H, OCH2CH3), 5.20(d, J = 3.0 Hz, 1H, CH-Ar), 6.78–6.82 (m,3H, Ar-H), 7.15(br s, N–H), 8.90(br s, N–H); 13C NMR (50 MHz, DMSO-d6): δ 164.6, 152.7, 152.1, 147.6, 147.1, 136.3, 117.5, 110.2, 109.2, 98.5, 58.5, 54.9, 53.2, 24.7, 14.0; EIMS: m/z [M+1]+: 321.

4.5

4.5 4-(4-Methoxy-phenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylicacid ethyl ester (4c-1)

Mp 201–202 °C; IR (KBr): 3223, 3095, 2929, 2833, 1710, 1655, 1512 cm−1; 1H NMR (200 MHz, DMSO-d6): δ 1.15(t, J = 7.2 Hz, 3H CH3), 2.24 (s, 3H, CH3), 3.80 (s, 3H, OCH3), 4.01 (q, J = 8.2 Hz, 2H, OCH2CH3), 5.18 (d, J = 3.0 Hz, 1H, CH-Ar), 6.88 (d, J = 8.2 Hz, 2H, Ar-H), 7.28 (d, J = 8.2 Hz), 7.24 (br s, N–H), 8.90(br s, N–H); 13C NMR (50 MHz, DMSO-d6): δ 165, 158.8, 152, 147.7, 137, 127.1, 113.7, 97.8, 58.6, 54.6, 53.4, 17.6, 13.9; EIMS: m/z [M+1]+: 291.

4.6

4.6 4-(4Chloro-phenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylicacid ethyl ester (4d-1)

Mp 217–218 °C; IR (KBr): 3237, 3117, 2978, 1701, 1647, 1460, 1288, 1221, 1088, 781 cm−1; 1H NMR (200 MHz, DMSO-d6): δ 1.09 (t, 3H, J = 7.2 Hz, OCH2–CH3), 2.25 (s, 3H, CH3), 3.98 (q, 2H, J = 7.2 Hz, OCH2–CH3), 5.14 (d, 1H, J = 3.0 Hz, CH-Ar), 7.25 (d, 2H, J = 8.4 Hz, Ar-H), 7.39 (d, 2H, J = 8.4 Hz, Ar-H), 7.77 (s, 1H, NH), 9.24 (s, 1H, NH); 13C NMR (50 MHz, DMSO-d6): δ 165.7 152.4, 149, 144.3, 132.2, 128.9, 128.6, 99.3, 59.7, 53.9, 18.3, 14.5; EIMS: m/z [M+1]+ 295.08.

4.7

4.7 4-(2Chloro-phenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylicacid ethyl ester (4e-1)

Mp 223–224 °C; IR (KBr): 3354, 3223, 3107, 2978, 1694, 1639, 1450, 1368, 1230, 1098, cm−1;1H NMR (200 MHz, DMSO-d6): δ 0.97 (t, 3H, J = 7.2 Hz, CH3). 2.28 (s, 3H, CH3), 3.87 (q, 2H, J = 7.2 Hz, OCH2–CH3), 5.61 (d, 1H, J = 2.8 Hz, CH-Ar), 7.24–7.40 (m, 4H, Ar-H), 7.68 (s, 1H, NH), 9.25 (s, 1H, NH); 13C NMR (50 MHz, DMSO-d6): δ 165.4, 151.8, 149.8, 142.2, 132.1, 129.8, 129.5, 129.2, 128.2, 98.3, 59.5, 51.9, 18.1, 14.4, EIMS: m/z [M+1]+: 295.08.

4.8

4.8 4-(2,4-Dimethoxy-phenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylicacid ethyl ester (4f-1)

Mp 200–202 °C; IR (KBr): 3223, 3095, 2929, 2833, 1710, 1655, 1512 cm−1; 1H NMR (200 MHz, DMSO-d6): δ 1.15 (t, J = 7.2 Hz, 3H CH3), 2.24 (s, 3H, CH3), 3.81 (s, 3H, OCH3), 3.85 (s, 3H, OCH3), 4.01 (q, J = 8.2 Hz, 2H, OCH2CH3), 5.18 (d, J = 3.2 Hz, 1H, CH-Ar), 6.38 (d, J = 7.8 Hz, 2H, Ar-H), 7.28 (s, 1H, Ar-H), 6.80 (br s, N–H), 6.90 (d, J = 7.8 Hz, 2H, Ar-H), 9.00 (br s, N–H); 13C NMR (50 MHz, DMSO-d6); δ 164.6, 153.7, 152.1, 148.6, 147.1, 136.3, 116.5, 112.2, 105.2, 98.5, 59.5, 54.9, 53.2, 23.7, 13.0. EIMS: m/z [M+1]+: 320.

4.9

4.9 4-(3-Nitro-phenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid ethyl ester (4g-1)

Mp 229–230 °C; IR (KBr): 3238, 3123, 2986, 1730, 1705, 1645, 1522, 1348, 1219, 1096, 854, 783 cm−1; 1H NMR (200 MHz, DMSO-d6): δ 1.10 (t, 3H, J = 7.2 Hz, CH3), 2.27 (s, 3H, CH3), 3.99 (q, 2H, J = 7.2 Hz, OCH2–CH3), 5.27 (d, 1H, J = 3.0 Hz, CH-Ar), 7.50 (d, 2H, J = 8.6 Hz, Ar-H), 7.89 (s, 1H, NH), 8.22 (d, 2H, J = 8.6 Hz, Ar-H), 9.35 (s, 1H, NH); 13C NMR (50 MHz, DMSO-d6): δ 165.5, 152.5, 152.2149.9147.2 128.1, 124.3, 98.6, 59.9, 54.1, 18.3,14.5; EIMS m/z [M+1]+: 306.10.

4.10

4.10 4-(4-Hydroxy-phenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid ethyl ester (4h-1)

Mp 234–235 °C; IR (KBr): 3235, 3113, 2955, 1703, 1647, 1514, 1456, 1279, 1221, 1088, 837, 791 cm−1; 1H NMR (200 MHz, DMSO-d6): δ 1.10 (t, 3H, J = 7.2 Hz, CH3); 2.25 (s, 3H, CH3), 3.98 (q, 2H, J = 7.2 Hz, OCH2–CH3), 5.09 (d, 1H, J = 3.0 Hz, CH-Ar), 6.87 (d, 2H, J = 8.6 Hz, Ar-H), 7.15 (d, 2H, J = 8.6 Hz, Ar-H), 7.67 (s, 1H, NH), 9.13 (s, 1H, NH); 13C NMR (50 MHz, DMSO-d6): δ 166.8, 157.9, 150.6, 147.5, 136.5, 125.9, 112.2, 100.0, 56.5, 53.8, 18.2, 15.6; EIMS m/z [M+1]+: 277.12.

4.11

4.11 4-(3,4,5-Trimethoxy-phenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid ethyl ester (4i-1)

Mp 171–173 °C; IR (KBr): 3350, 3220, 3190, 2984, 1668, 1650, 1620 cm−1;1H NMR (200 MHz, DMSO-d6): δ 1.15 (t, J = 7.2 Hz, 3H OCH2CH3), 2.14 (s, 3H, CH3), 3.86 s, 9H, 3xOCH3), 4.01 (q, J = 7.2 Hz, 2H, OCH2CH3), 5.20 (d, 1H, J = 3.0 Hz, CH-Ar), 6.78–6.82 (m, 3H, Ar-H), 7.15 (br s, N–H), 8.90 (br s, N–H); 13C NMR (50 MHz, DMSO-d6): δ 164.6152.3, 152.7, 152.1, 147.6, 147.1, 136.3, 117.5, 110.2, 109.2, 98.5, 58.5, 54.9, 53.2, 24.7, 14.0; EIMS: m/z[M+1]+: 320.

4.12

4.12 4Phenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid ethyl ester (4j-1)

Mp 202–204 °C; IR (KBr): 3256, 3121, 2945, 1730, 1703, 1647, 1464, 1290, 1226, 1090, 756 cm−1; 1H NMR (200 MHz, DMSO-d6): δ 1.09 (t, 3H, J = 7.0 Hz, CH3); 2.25 (s, 3H, CH3), 3.98 (q, 2H, J = 7.0 Hz, OCH2–CH3), 5.15 (d, 1H, J = 3.2 Hz, CH-Ar), 7.21–7.35 (m, 5H, Ar-H), 7.73 (s, 1H, NH), 9.19 (s, 1H, NH); 13C NMR (50 MHz, DMSO-d6): δ 165.8, 152.6, 148.8, 145.3, 128.8, 127.7, 126.7, 99.7, 59.6, 54.4, 18.2 14.5; EIMS m/z [M+1]+: 261.12.

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