B. Shwetha et al.
Bioorganic Chemistry 108 (2021) 104586
1
LC-MS purity = 97.9%; (R
f
= 0.54 in hexanes:EtOAc 1:2 v/v); H NMR
4.2.3.7. Synthesis of N-benzyl-5-(4-chlorophenyl)furan-2-carboxamide
(SH07). Following the general procedure A, compound SH07 was ob-
tained from compound 3 (100 mg, 0.45 mmol, 1 equivalent) and ben-
zylamine (59 µl, 0.54 mmol, 1.2 equivalent) as off white solid with 75%
(
400 MHz, DMSO‑d
6
) δ 9.46 (s, 1H, –OH), 9.02–9.00 (t, J = 5.7 Hz, 1H,
–
2
CONH), 7.95–7.93 (d, J = 8.4 Hz, 2H, Ar-H), 7.53–7.51 (d, J = 8.4 Hz,
H, Ar-H), 7.18–7.11 (m, 4H, Ar-H), 6.71–6.69 (d, J = 8.2 Hz, 2H, Ar-H),
13
4
.35–4.33 (d, J = 5.9 Hz, 2H,–CH
2
). C NMR (100 MHz, DMSO‑d
6
) δ
yield (105 mg); LC-MS purity = 93.7%; (R = 0.65 in hexanes:EtOAc 1:2
f
1
1
57.84, 156.92, 153.66, 147.80, 133.35, 129.85, 129.30,
v/v); HNMR (300 MHz, DMSO‑d
6
) δ 9.12 (t, J = 6.0 Hz, 1H, –CONH),
1
29.04,128.69, 126.42, 116.02, 115.48, 108.60. Found ESI/HRMS (m/
7.97–7.94 (d, J = 8.4 Hz, 2H, Ar-H), 7.55–7.53 (d, J = 8.4 Hz, 2H, Ar-H),
+
35
+
37
z) 328.1 [M+H]
(
Cl), 330.1 [M+H]
(
Cl), Calculated for
7.34–7.33 (d, J = 3.0 Hz, 4H, Ar-H), 7.28–7.15 (m, 3H, Ar-H), 4.49–4.47
+
35
+
37
13
C
18
H
14ClNO
3
[M + H]
(
Cl): 328.07, [M + H]
(
Cl): 330.07.
(d, J = 6.0 Hz, 2H, –NH-CH
2 6
). C NMR (100 MHz, DMSO‑d ) δ 157.99,
1
53.74, 147.67, 139.87, 133.40, 129.32, 128.70, 127.68, 127.21,
+
35
4
.2.3.3. Synthesis of 5-(4-chlorophenyl)-N-(3,5-difluorophenyl)furan-2-
126.43, 116.17, 108.66. ESI/HRMS (m/z) 312.1 [M+H]
( Cl), 314.1
+
+
37
[M+H] (35Cl): 312.07,
+
carboxamide (SH03):. Following the general procedure A, compound
SH03 was obtained from compound 3 (100 mg, 0.45 mmol, 1 equiva-
lent) and 3,5-difluoroaniline (116 mg, 0.9 mmol, 2 equivalent) as off
[M+H]
[M+H]
(
Cl) Calculated for C18
H14ClNO
2
(
37Cl): 314.07.
white solid with 50% yield (75 mg); LC-MS purity = 99.4%; (R
f
= 0.73 in
) δ 10.49 (s, 1H,
CONH), 8.01–7.99 (d, J = 8.6 Hz, 2H, Ar-H), 7.60–7.54 (m, 4H, Ar-H),
4.2.3.8. Synthesis of N-(5-chloro-2-methoxypyrimidin-4-yl)-5-(4-chlor-
ophenyl)furan-2-carboxamide (SH08). Following the general procedure
A, compound SH08 was obtained from compound 3 (100 mg, 0.45
mmol, 1 equivalent) and 5-chloro-2-methoxypyrimidin-4-amine (86 mg,
1
hexanes:EtOAc 1:2 v/v); HNMR (400 MHz, DMSO‑d
6
–
7
.47–7.46 (d, J = 3.6 Hz, 1H, Ar-H), 7.28–7.27 (d, J = 3.6 Hz, 1H, Ar-H),
13
7
.02–6.97 (t, J = 9.4 Hz, 1H, Ar-H); C NMR (100 MHz, DMSO‑d
6
) δ
0.54 mmol, 1.2 equivalent) as off white solid with 70% yield (115 mg);
1
1
63.91, 161.65, 161.40, 155.98, 154.97, 146.65, 134.10, 133.89,
LC-MS purity = 94.3%;(R
(300 MHz, DMSO‑d
f
= 0.68 in hexanes:EtOAc 1:2 v/v); H NMR
1
29.47, 127.04, 126.77, 120.18, 118.38, 109.30, 103.76, 103.47.
6
) δ 11.56 (s, 1H, –CONH), 8.04–8.01 (d, J = 8.7 Hz,
+
35
+
37
Found ESI/HRMS (m/z) 334 [M + H]
(
Cl), 336 [M + H]
(
Cl),
+
2H, Ar-H), 7.90 (s, 1H, Ar-H), 7.70–7.68 (d, J = 3.9 Hz, 1H, Ar-H),
+
35
Calculated for C17
H
10ClF
2
NO
2
[M + H] : 334.04 ( Cl), [M + H]
7.58–7.55 (d, J = 9.0 Hz, 2H, Ar-H), 7.27–7.26 (d, J = 3.0 Hz, 1H, Ar-
3
7
13
(
Cl): 336.04.
H), 3.95 (s, 3H, –OCH
1
3 6
). C NMR (100 MHz, DMSO‑d ) δ 164.72,
61.71, 161.64, 157.53, 155.81, 145.98, 133.98, 129.35, 128.24,
+
+
4
.2.3.4. Synthesis of N-(2-bromophenethyl)-5-(4-chlorophenyl)furan-2-
126.93, 119.96, 109.20, 103.64, 55.57. ESI/HRMS (m/z) 364 [M+H]
3
3
5
5
+
37
carboxamide (SH04):. Following the general procedure A, compound
SH04 was obtained from compound 3 (100 mg, 0.45 mmol, 1 equiva-
lent) and 2-(2-bromophenyl)ethanamine (78 µl, 0.539 mmol, 1.2
(
(
Cl), 366 [M+H]
(
+
Cl). Calculated for C16
H11Cl
N
2 3
O
3
[M+H]
Cl): 364.02, [M+H] (37Cl): 366.02.
equivalent) as pale yellow solid with 74% yield (135 mg); LC-MS purity
4.2.3.9. Synthesis of 5-(4-chlorophenyl)-N-(2,5-dichloropyrimidin-4-yl)
furan-2-carboxamide (SH09):. Following the general procedure A,
compound SH09 was obtained from compound 3 (100 mg, 0.45 mmol, 1
equivalent) and 2,5-dichloropyrimidin-4-amine (74 mg, 0.54 mmol, 1.2
1
=
96.6%; (R
DMSO‑d
H), 7.62–7.54 (m, 3H, Ar-H), 7.35–7.31 (m, 2H, Ar-H), 7.20–7.14 (m,
f
= 0.65 in hexanes:EtOAc 1:2 v/v); H NMR (400 MHz,
6
) δ 8.70–8.69 (t, J = 5.5 Hz,1H, –CONH), 8.67–7.92 (m, 2H, Ar-
3
H, Ar-H), 3.53–3.48 (m, 2H, -N-CH ), 3.01–2.97 (t, J = 7.8 Hz 2H,
2
equivalent) as pale yellow solid with 70% yield (116 mg); LC-MS purity
1
3
1
–
CH
2
). C NMR (100 MHz, DMSO‑d ) δ 157.98, 153.60, 147.77,
6
= 95.7%; (R
DMSO‑d
7.8 Hz, 2H, Ar-H), 7.95 (s, 1H, Ar-H), 7.74–7.72 (d, J = 6.0 Hz, 2H, Ar-
f
= 0.78 in hexanes:EtOAc 1:2 v/v); H NMR (300 MHz,
1
38.83, 133.37, 132.94, 131.40, 129.32, 128.86, 128.70, 128.26,
6
) δ 12.03 (s, 1H, –CONH), 8.24, (s, 1H, Ar-H), 8.07–8.04 (d, J =
1
26.39, 124.30, 115.87, 108.60. Found ESI/HRMS (m/z) 404.0 [M +
+
+
35
+
37
13
H]
H]
(
Cl), 406 [M + H]
(
Cl), Calculated for C19
H
15BrClNO
2
[M +
H), 7.59–7.56 (d, J = 9.0 Hz, 1H, Ar-H). C NMR (100 MHz, DMSO‑d
6
) δ
35
Cl) 404.0, [M + H]+ (37Cl): 406.
(
161.85, 161.47, 158.77, 157.37, 156.20, 145.54, 134.14, 129.39,
+
1
28.14, 127.05, 120.63, 109.38, 108.71. ESI/HRMS (m/z) 368 [M+H]
3
5 37 35
+
+
4
.2.3.5. Synthesis of 5-(4-chlorophenyl)furan-2-carboxamide (SH05).
(
Cl), 370 [M+H] ( Cl). Calculated for C15
H
8
Cl
3
3
N O
2
[M+H] ( Cl):
+
37
Following the general procedure A, compound SH05 was obtained from
367.97, [M+H]
( Cl): 369.97.
compound 3 (100 mg, 0.45 mmol, 1 equivalent) and aqueous ammonia
solution (0.1 mL) as off white solid with 81% yield (81 mg); LC-MS
4.2.3.10. Synthesis of 5-(4-chlorophenyl)-N-(1-phenylethyl)furan-2-car-
boxamide (SH10). Following the general procedure A, compound SH10
was obtained from compound 3 (100 mg, 0.45 mmol, 1 equivalent) and
1-phenylethanamine (65 mg, 0.54 mmol, 1.2 equivalent) as pale brown
1
purity = 94.2%; (R
MHz, DMSO‑d
) δ 7.98 (s, 2H, –CO-NH
Ar-H), 7.54–7.51 (d, 2H, J = 8.0 Hz, Ar-H), 7.45 (s, 1H, Ar-H), 7.16–7.12
m, 2H, Ar-H). 13C NMR (100 MHz, DMSO‑d
) δ 159.60, 153.66, 147.92,
33.33, 129.32, 128.73, 126.40, 116.16, 108.61. Found ESI/HRMS (m/
f
= 0.32 in hexanes:EtOAc 1:2 v/v); H NMR (400
6
2
), 7.93–7.91 (d, J = 8.0 Hz, 1H,
(
6
solid with 75% yield (110 mg); LC-MS purity = 95.8%; (R
f
= 0.65 in
1
1
hexanes:EtOAc 1:2 v/v); H NMR (300 MHz, DMSO‑d
6
) δ 8.85–8.82 (d,
+
35
+
37
z) 222 [M+H]
(
Cl), 224 [M+H]
(
Cl). Calculated for
37Cl) : 224.02.
J = 9.0 Hz, 1H, –CONH), 7.98–7.95 (d, J = 9.0 Hz, 2H, Ar-H), 7.56–7.53
(d, J = 9.0 Hz, 2H, Ar-H), 7.42–7.31 (m, 4H, Ar-H), 7.29–7.21 (m, 2H,
Ar-H), 7.16–7.14 (d, J = 3.6 Hz, 1H, Ar-H), 5.22–5.17 (t, J = 7.2 Hz, 1H,
+
+
C
11
H
8
ClNO
2
[M + H] (35Cl) : 222.02, [M + H]
(
1
3
N-CH), 1.53–1.51 (d, J = 9.6 Hz, 3H, -N
3
C CH ). C NMR (100 MHz,
– –
4
.2.3.6. Synthesis of 5-(4-chlorophenyl)-N-(3-nitrophenyl)furan-2-car-
boxamide (SH06). Following the general procedure A, compound SH06
DMSO‑d
6
) δ 157.27, 153.84, 147.77, 144.87, 133.44, 129.37, 128.77,
was obtained from compound 3 (100 mg, 0.45 mmol, 1 equivalent) and
128.70, 127.14, 126.57, 116.32, 108.70, 48.10. Found ESI/HRMS (m/z)
+
35
+
37
3
4
1
8
7
7
-nitroaniline (125 mg, 0.9 mmol, 2 equivalent) as yellow solid with
6% Yield (32 mg); LC-MS purity = 94.9%; (R = 0.70 in hexanes:EtOAc
:2 v/v); 1H NMR (400 MHz, DMSO‑d
) δ 10.96 (S, 1H, –CONH),
326.09 [M+H]
(
Cl), 328.09[M+H]
(
Cl). Calculated for
+
C
19
H
16ClNO
2
[M+H] (35Cl): 326.09, [M+H]+ (37Cl):328.09. Calcu-
f
lated for M+H.
6
.10–8.08 (d, J = 8.4 Hz, 1H, Ar-H), 8.0–7.97 (t, J = 6.0 Hz, 3H, Ar-H),
.81–7.78 (t, J = 7.2 Hz, 1H, Ar-H), 7.61–7.59 (d, J = 8.4 Hz, 2H, Ar-H),
.45–7.41 (t, J = 4.0 Hz, 2H, Ar-H), 7.29–7.28 (d, J = 3.6 Hz, 1H, Ar-H).
4.2.4. General procedure ’b’ for synthesis of compounds SH11, SH13 &
SH19
1
3
C NMR (100 MHz, DMSO‑d
6
) δ 156.08,154.84, 146.48, 141.66,
To an ice-cold suspension of 5-phenylfuran-2-carboxylic acid (4)
(100 mg, 0.53 mmol, 1 equivalent) in dimethyl formamide (1.5 mL),
carbonyldiimidazole (1.5 to 2.0 equivalent) was added under nitrogen
atmosphere, then the resulting reaction mixture was warmed to room
1
1
35.04, 133.96, 131.97, 129.52, 128.26, 126.55, 125.68, 125.26,
3
5
18.63, 109.39. Found m/z (ESI–MS) 341.1 [M - H]‾ ( Cl), 342.1 [M -
3
7
35
2 4
H]‾ ( Cl), calculated for C17H11ClN O [M - H]‾ ( Cl): 341.04.
1
1