Chemistry & Biodiversity
10.1002/cbdv.201900097
Chem. Biodiversity
1
ethyl -2-amino-6-(1,2,3,4-tetrahydronaphthalen-1-yl)-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxylate 4g,h: 61% yield. H
NMR (400 MHz, CDCl
3
) δ (ppm): 7.75 – 7.69 (m, 1H, Ar H), 7.17 – 7.11 (m, 2H, Ar H), 7.09 – 7.04 (m, 1H, Ar H), 5.92 (s, 2H, NH
), 4.00 (dd, J = 9.3, 4.4, 1H, CH), 3.63 (d, J = 14.1, 1H, CH ), 3.49 (d, J = 14.1, 1H, CH ), 2.92 – 2.59 (m, 6H, CH
), 1.79 – 1.68 (m, 2H, CH ), 1.32 (t, J = 7.1, 3H, -OCH CH
). 13C NMR (101 MHz, CDCl3) δ (ppm): 166.0 (C=O), 161.9 (C2),
38.3 (Ar) , 138.1 (Ar), 131.4 (C 3a), 128.8 (Ar), 128.2 (Ar), 126.4 (Ar), 125.8 (Ar), 116.1 (C 7a), 105.6 (C3), 62.6 (CH), 59.5 (CH ), 47.1 (C7), 46.0
), 28.7 (C4), 21.8 (CH ), 21.7 (CH ), 14.5 (CH ). Elemental Analysis calculated for C20 S: C, 67.39; H, 6.79; N, 7.86; found:
C, 67.44; H, 6.75; N, 7.81. [α] 20
(c=1.00, CHCl ): + 54.8 (S enantiomer)
General procedure for the synthesis of compounds 2a-h
2
), 4.26 (q, J =
7
1
1
.1, 2H, -OCH
2
CH
3
2
2
2
), 2.02 (dd, J =
0.5, 4.0, 2H, CH
2
2
2
3
2
(C5), 29.7 (CH
2
2
2
3
H
24
N
2
O
2
D
3
To a stirred solution of amino thiophene (1eq) dissolved in Dichloromethane (DCM-10 ml) Triethylamine (TEA-2 eq) and 4-Nitrobenzoyl
chloride (3 eq) were added. The resulting mixture was stirred at room temperature for 72 hours and the reaction was monitored by TLC.
To completion the reaction was extracted three times with Sodium bicarbonate (NaHCO3). The organic layer was then dried over by
NaSO4, filtered and concentrated in vacuo. A crude compound was obtained that was purified by silica gel column chromatography
(
eluent: Hexane/EtOAc 4:1).
ethyl 6-benzyl-2-(4-nitrobenzamido)-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxylate 2a: 84% yield. H NMR (400 MHz,
CDCl ) δ (ppm): 12.48 (s, 1H, NH), 8.37 (d, J = 8.7, 2H, Ar H), 8.18 (d, J = 8.7, 2H, Ar H), 7.44 – 7.29 (m, 5H, Ar H), 4.39 (q, J = 7.1, 2H, -
OCH CH ), 3.73 (s, 2H, CH ), 3.63 (s, 2H, CH ), 2.93 (d, J = 6.0, 2H, CH ), 2.81 (t, J = 5.8, 2H, CH ), 1.40 (t, J = 7.1, 3H, -OCH CH
). 13C NMR (101
MHz, CDCl ) δ (ppm): 167.0 (C3), 163.1 (C=O), 153.3 (C=O), 151.9 (Ar), 149.0 (Ar), 144.1 (Ar), 138.3 (Ar), 137.9 (Ar), 129.2 (2C, Ar), 128.7 (2C,
Ar), 128.4 (2C, Ar), 127.4 (2C, Ar, C 3a), 124.2 (C 7a), 118.1 (C3), 62.1 (CH
Analysis calculated for C24 S: C, 61.92; H, 4.98; N, 9.03; found: C, 61.86; H, 5.02; N, 9.00
1
3
2
3
2
2
2
2
2
3
3
2
), 61.0 (CH
2
), 51.4 (C7), 50.1 (C5), 26.9 (C4), 14.3 (CH
3
). Elemental
H
23
N
3
O
5
1
ethyl 6-(4-fluorobenzyl)-2-(4-nitrobenzamido)-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxylate 2b: 88% yield. H NMR (400
MHz, CDCl
H), 4.39 (q, J = 7.1, 2H, -OCH
OCH CH
). 13C NMR (101 MHz, CDCl
Ar), 137.8 (Ar), 130.6 (d, J = 8.1, 2C, Ar), 129.7 (C 3a), 128.7 (2C, Ar), 125.3 (C 7a), 124.2 (2C), 115.3(d, J = 20.9, 2C, Ar), 113.2 (C3), 61.2 (CH
3
) δ (ppm): 12.48 (s, 1H, NH), 8.37 (d, J = 8.6, 2H, Ar H), 8.18 (d, J = 8.6, 2H, Ar H), 7.38 – 7.30 (m, 2H, Ar H), 7.03 (t, J = 8.6, 2H, Ar
CH ), 3.68 (s, 2H, CH ), 3.61 (s, 2H, CH ), 2.92 (s, 2H, CH ), 2.78 (t, J = 5.8, 2H, CH ), 1.40 (t, J = 7.1, 3H, -
) δ(ppm): 169.9 (C2), 167.6 (C=O), 163.1-161.5 (d, J = 240, Ar), 162.2 (C=O), 160.4 (Ar), 148.3 (Ar), 143.2
),
2
3
2
2
2
2
2
3
3
(
2
61.1 (CH
2
), 51.4 (C7), 50.0 (C5), 26.9 (C4), 14.3 (CH
3
). Elemental Analysis calculated for C24
H
22FN
3
O
5
S: C, 59.62; H, 4.59; N, 8.69; found: C,
59.71; H, 5.02; N, 8.60
1
ethyl 2-(4-nitrobenzamido)-6-(pyridin-3-ylmethyl)-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxylate 2c: 81% yield. H NMR
(
400 MHz, CDCl
.8, 2H, Ar H), 7.74 (d, J = 8.1, 1H, Ar H), 7.32 – 7.27 (m, 1H, Ar H), 4.39 (q, J = 7.2, 2H, -OCH
5.9, 2H, CH ), 2.80 (t, J = 5.8, 2H, CH ), 1.40 (t, J = 7.1, 3H, -OCH CH
). 13C NMR (101 MHz, CDCl
C=O), 152.2 (Ar), 150.3 (Ar), 148.7 (Ar), 144.0 (Ar), 139.9 (Ar), 136.8 (Ar), 133.8 (Ar), 130.7 (C 3a), 128.7 (2C, Ar), 124.2 (2C, Ar), 123.1 (C 7a),
3
) δ (ppm): 12.49 (s, 1H, NH), 8.61 (d, J = 2.1, 1H, Ar H), 8.55 (dd, J = 4.7, 1.7, 1H, Ar H), 8.40 – 8.36 (m, 2H, Ar H), 8.18 (d, J =
CH ), 3.74 (s, 2H, CH ), 3.65 (s, 2H, CH ), 2.93 (d, J
) δ (ppm): 168.2 (C2), 165.5 (C=O), 162.1
8
2
3
2
2
=
2
2
2
3
3
(
113.7 (C3), 61.1 (CH
2
), 59.2 (CH
2
), 51.5 (C7), 49.9 (C5), 26.8 (C4), 14.8 (CH
3
). Elemental Analysis calculated for C23
H
22
N
4
O
5
S: C, 59.22; H, 4.75;
N, 12.01; found: C, 59.30; H, 4.79; N, 12.10
1
ethyl- 2-(4-nitrobenzamido)-6-(1-phenylethyl)-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxylate 2d: 79% yield. H NMR (400
MHz, CDCl
OCH CH ), 3.91 (d, J = 14.8, 1H, CH
.40 (t, J = 7.1, 3H, -OCH CH
). 13C NMR (101 MHz, CDCl
30.2 (C 3a), 128.7 (2C. Ar), 128.5 (2C, Ar), 127.5 (2C, Ar), 124.2 (2C, Ar), 123.4 (C 7a), 121.1 (Ar), 112.4 (C3), 64.0 (CH
3
) δ(ppm): 12.46 (s, 1H,NH), 8.37 (d, J = 8.9, 2H, Ar H), 8.17 (d, J = 8.8, 2H, Ar H), 7.51 – 7.30 (m, 5H, Ar H), 4.38 (q, J = 7.1, 2H, -
), 3.85 (q, J = 6.8, 1H, CH), 3.75 (d, J = 14.9, 1H, CH ), 3.11 – 2.71 (m, 4H, CH ), 1.59 (d, J = 6.7, 3H, CH
) δ (ppm): 167.0 (C2), 161.2 (C=O), 158.2 (C=O), 150.2 (Ar), 147.6 (Ar), 143.9 (Ar),
), 61.0 (CH), 49.1 (C7),
2
3
2
2
2
2
),
1
1
4
2
3
3
2
7.7 (C5), 27.1 (C4), 20.4 (CH
3
),14.3 (CH
3
). Elemental Analysis calculated for C25
H
25
N
3
O
5
S: C, 62.62; H, 5.25; N, 8.76; found: C, 62.55; H, 5.21;
N, 8.80
1
ethy-6-(1-cyclohexylethyl)-2-(4-nitrobenzamido)-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxylate 2e,f: 88% yield. H NMR
(
400 MHz, Chloroform-d) δ (ppm): 12.48 (s, 1H, NH), 8.37 (d, J = 8.8, 2H, Ar), 8.18 (d, J = 8.8, 2H, Ar), 4.39 (q, J = 7.1, 2H, -OCH
14.3, 1H, CH ), 3.56 (d, J = 14.5, 1H, CH ), 2.99 – 2.76 (m, 4H, CH ), 2.67 – 2.54 (m, 1H, Cy), 2.50 – 2.39 (m, 1H, Cy), 1.88 – 1.59 (m, 2H, Cy),
.42 (t, J = 7.1, 3H, -OCH CH ), 1.33 – 1.11 (m, 4H, Cy), 1.01 (d, J = 6.6, 3H, CH ), 0.96 – 0.75 (m, 2H, CH ) δ (ppm):
). 13C NMR (101 MHz, CDCl
67.0 (C2), 161.2 (C=O), 150.1 (C=O), 147.4 (Ar), 137.9 (Ar), 130.3 (C 3a), 128.6 (2C, Ar), 124.1 (2C, Ar), 123.2 (C 7a), 112.5 (C3), 65.8 (CH),
3.7 (CH ), 60.9 (CH ), 47.5 (C7), 45.6 (C5), 41.1 (CH ), 31.1 (CH ), 30.1 (CH ), 27.8 (CH ), 26.7 (C4), 26.5 (CH ), 14.3 (CH ), 10.3 (CH ).
S: C, 61.84; H, 6.43; N, 8.65; found: C, 61.93; H, 6.47; N, 8.60. [α] (c=1.00, CHCl ): + 16.1 (S
2
CH ), 3.74 (d, J
3
=
2
2
2
1
1
6
2
3
3
2
3
2
2
2
2
2
2
2
3
3
2
0
Elemental Analysis calculated for C25
enantiomer)
H
31
N
3
O
5
D
3
7
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