32
B. Sauer et al. / European Journal of Medicinal Chemistry 127 (2017) 22e40
2.27e2.21 (m, 2H, CH2). 13C NMR (101 MHz, CDCl3)
d
168.90, 152.15,
4H, piperidineeH), 1.61e1.52 (m, 4H, piperidineeH), 1.45e1.35 (m,
2H, piperidineeH). 13C NMR (101 MHz, CDCl3)
169.46, 151.85,
149.48, 134.21, 133.75, 132.81, 132.76, 126.18, 124.32, 120.36, 118.82,
118.79, 113.43, 111.27, 111.23, 57.04, 54.20, 35.56, 34.31, 24.97, 23.58.
ESI-MS: m/z: 439.18 [MþH]þ.
149.49, 144.06, 133.98, 133.54, 132.93, 132.89, 128.79, 127.78,
126.68, 126.04, 124.43, 119.83, 118.75, 118.65, 112.99, 111.58, 111.57,
49.41, 39.10, 35.23, 34.55. ESI-MS: m/z: 520.16 [MꢃH]-.
d
5.1.14.8. N-(2-(Methylthio)ethyl)-2-[2,5-bis(4-cyanophenyl)furan-3-
yl]acetamide (13h). Off-white solid (52% yield). 1H NMR (400 MHz,
5.1.14.14. N-[2-(Morpholin-4-yl)ethyl]-2-[2,5-bis(4-cyanophenyl)
DMSO)
d
8.31 (t, J ¼ 5.4 Hz, 1H, CONH), 8.00 (d, J ¼ 8.4 Hz, 4H, Ar-H),
furan-3-yl]acetamide (13n). Off-white solid (47% yield). 1H NMR
7.96e7.87 (m, 4H, Ar-H), 7.31 (s, 1H, furan-H), 3.61 (s, 2H, furan-
CH2), 3.30e3.25 (m, 2H, CH2CH2S), 2.58e2.52 (m, 2H, CH2CH2S),
(400 MHz, CDCl3)
d
7.97 (d, J ¼ 8.3 Hz, 2H, Ar-H), 7.82 (d, J ¼ 8.4 Hz,
2H, Ar-H), 7.74 (d, J ¼ 8.5 Hz, 2H, Ar-H), 7.68 (d, J ¼ 8.4 Hz, 2H, Ar-H),
7.26 (m, 1H, furan-H, CHCl3), 4.40e3.82 (m, 6H), 3.81e3.64 (m, 4H,
furan-CH2), 3.59e3.32 (m, 2H), 3.01e2.74 (m, 2H), 1.72e1.52 (m,
2H). ESI-MS: m/z: 441.13 [MþH]þ.
2.06 (s, 3H, CH3). 13C NMR (101 MHz, DMSO)
d 168.78, 150.63,
148.40, 133.91, 133.34, 132.96, 132.74, 125.92, 124.25, 121.64, 118.77,
118.76, 114.41, 109.86, 109.81, 38.13, 32.94, 32.69, 14.50. ESI-MS: m/
z: 400.08 [MꢃH]-.
5.1.14.15. N-[2-(4-Methylpiperazin-1-yl)ethyl]-2-[2,5-bis(4-
cyanophenyl)furan-3-yl]acetamide (13o). The compound was used
for the next step without purification. ESI-MS: m/z: 454.19 [MþH]þ.
5.1.14.9. N-(3-(Methylthio)propyl)-2-[2,5-bis(4-cyanophenyl)furan-
3-yl]acetamide (13i). Light yellow solid (61% yield). 1H NMR
(400 MHz, CDCl3)
d
7.81 (d, J ¼ 8.4 Hz, 4H, Ar-H), 7.77e7.68 (m, 4H,
Ar-H), 6.92 (s, 1H, furan-H), 3.66 (s, 2H, furan-CH2), 3.40 (dd,
J ¼ 12.1, 6.3 Hz, 2H, CH2CH2CH2S), 2.46 (t, J ¼ 6.9 Hz, 2H,
5.1.14.16. N-[3-(Dimethylamino)propyl]-2-[2,5-bis(4-cyanophenyl)
furan-3-yl]acetamide (13p). Light yellow solid (63% yield). 1H NMR
CH2CH2CH2S), 2.01 (s, 3H, CH3), 1.78 (p,
J
¼
6.8 Hz, 2H,
(400 MHz, CDCl3)
d
7.97 (s,1H, CONH), 7.86 (d, J ¼ 8.4 Hz, 2H, AreH),
CH2CH2CH2S). 13C NMR (101 MHz, CDCl3)
d
168.94, 152.00, 149.36,
7.82 (d, J ¼ 8.4 Hz, 2H, Ar-H), 7.76e7.72 (m, 2H, Ar-H), 7.70 (d,
J ¼ 8.4 Hz, 2H, AreH), 7.01 (s, 1H, furaneH), 3.64 (s, 2H, furaneCH2),
3.42e3.38 (m, 2H, CONHCH2), 2.47 (t, J ¼ 5.9 Hz, 2H, CH2N(CH3)2),
2.13 (s, 6H, CH2N(CH3)2), 1.75e1.66 (m, 2H, CH2CH2CH2). 13C NMR
133.85, 133.38, 132.74, 132.71, 125.91, 124.26, 119.64, 118.58, 118.49,
112.87, 111.41, 111.37, 39.26, 34.41, 31.90, 28.11, 15.46. ESI-MS: m/z:
414.10 [MꢃH]-.
(101 MHz, CDCl3)
d 169.51, 151.86, 149.57, 134.14, 133.66, 132.95,
5.1.14.10. N-(3-Hydroxypropyl)-2-(2,5-bis(4-cyanophenyl)furan-3-
132.85, 126.03, 124.32, 120.37, 118.78, 118.75, 113.56, 111.41, 111.38,
yl)acetamide (13j). White solid (76% yield). 1H NMR (400 MHz,
58.40, 44.69, 39.73, 34.63, 24.65. ESI-MS: m/z: 413.13 [MþH]þ.
DMSO)
d
8.14 (t, J ¼ 5.4 Hz, 1H, CONH), 8.04e7.97 (m, 4H, AreH),
7.96e7.88 (m, 4H, AreH), 7.30 (s, 1H, furaneH), 3.59 (s, 2H, fur-
aneCH2), 3.41 (t, J ¼ 6.3 Hz, 2H, CH2OH), 3.17e3.12 (m, 2H, CH2,
CONHCH2), 1.60e1.54 (m, 2H, CH2). 13C NMR (101 MHz, DMSO)
5.1.14.17. N-[4-(Dimethylamino)butyl]-2-[2,5-bis(4-cyanophenyl)
furan-3-yl]acetamide (13q). Light yellow solid (82% yield). 1H NMR
(400 MHz, DMSO)
d
8.25 (t, J ¼ 5.7 Hz,1H, CONH), 8.05e7.98 (m, 4H,
d
168.68, 150.63, 148.39, 133.95, 133.36, 132.96, 132.73, 125.91,
AreH), 7.97e7.89 (m, 4H, AreH), 7.32 (s, 1H, furaneH), 3.61 (s, 2H,
furaneCH2), 3.13e3.10 (m, 2H, CH2), 3.05e2.97 (m, 2H, CH2), 2.71 (s,
6H, CH3), 1.65e1.54 (m, 2H, CH2), 1.49e1.39 (m, 2H, CH2). 13C NMR
124.27, 121.84, 118.77, 114.36, 109.86, 109.80, 58.35, 36.06, 32.93,
32.27. ESI-MS: m/z: 384.16 [MꢃH]-.
(101 MHz, DMSO)
d 168.72, 150.67, 148.43, 133.94, 133.32, 132.98,
5.1.14.11. N-[2-(Dimethylamino)ethyl]-2-[2,5-bis(4-cyanophenyl)
132.75, 125.93, 124.27, 121.74, 121.73, 118.76, 114.30, 109.92, 109.85,
furan-3-yl]acetamide (13k). Light yellow solid (61% yield). 1H NMR
56.24, 42.07, 37.93, 32.97, 26.03, 21.16. ESI-MS: m/z: 427.18 [MþH]þ.
(400 MHz, CDCl3)
d 7.89e7.82 (m, 2H, AreH), 7.82e7.77 (m, 2H,
AreH), 7.75e7.71 (m, 2H, AreH), 7.71e7.66 (m, 2H, AreH), 6.99 (s,
1H, furaneH), 6.56 (s, 1H, CONH), 3.64 (s, 2H, furaneCH2),
3.40e3.36 (m, 2H, CONHCH2), 2.46 (t, J ¼ 5.7 Hz, 2H, CH2N(CH3)2),
5.1.14.18. 1-{[2,5-Bis(4-cyanophenyl)furan-3-yl]acetyl}piperidine
(13r). Off-white solid (71% yield). 1H NMR (400 MHz, CDCl3)
d
7.82e7.76 (m, 4H, AreH), 7.73 (d, J ¼ 8.5 Hz, 2H, AreH), 7.68 (d,
2.24 (s, 6H, CH2N(CH3)2). 13C NMR (101 MHz, CDCl3)
d
169.27,151.91,
J ¼ 8.5 Hz, 2H, AreH), 6.91 (s, 1H, furaneH), 3.77 (s, 2H, furaneCH2),
3.52 (s, 4H, piperidineeH), 1.71e1.62 (m, 2H, piperidineeH),
1.61e1.49 (m, 4H, piperidineeH). ESI-MS: m/z: 394.24 [MꢃH]-.
149.50, 134.26, 133.77, 132.84, 132.76, 126.27, 124.37, 120.19, 118.83,
118.79, 113.15, 111.33, 111.27, 57.81, 45.04, 36.92, 34.30. ESI-MS: m/z:
399.23 [MþH]þ.
5.1.14.19. 4-{[2,5-Bis(4-cyanophenyl)furan-3-yl]acetyl}morpholine
5.1.14.12. N-[2-(Diethylamino)ethyl]-2-[2,5-bis(4-cyanophenyl)
(13s). Light yellow solid (45% yield). 1H NMR (400 MHz, CDCl3)
furan-3-yl]acetamide (13l). Light yellow solid (70% yield). 1H NMR
d
7.79e7.74 (m, 4H, AreH), 7.74e7.70 (m, 2H, AreH), 7.69e7.64 (m,
2H, AreH), 6.88 (s, 1H, furaneH), 3.75 (s, 2H, furaneCH2),
3.72e3.59 (m, 6H, morpholineeH), 3.46 (s, 2H, morpholineeH). 13
NMR (101 MHz, CDCl3) 168.13, 152.01, 149.16, 134.35, 133.74,
(400 MHz, CDCl3)
d
7.86 (d, J ¼ 8.5 Hz, 2H, AreH), 7.79 (d, J ¼ 8.4 Hz,
2H, AreH), 7.72 (d, J ¼ 8.5 Hz, 2H, AreH), 7.68 (d, J ¼ 8.4 Hz, 2H,
AreH), 7.01e6.89 (m, 2H, furaneH, CONH), 3.64 (s, 2H, furaneC2),
3.41e3.37 (m, 2H, CONHCH2), 2.71e2.69 (m, 2H, CH2N(CH2CH3)2),
2.63e2.58 (m, 4H, CH2N(CH2CH3)2)), 0.97 (t, J ¼ 7.1 Hz, 6H,
C
d
132.84, 132.81, 126.34, 124.38, 119.99, 118.82, 118.70, 112.65, 111.44,
111.31, 66.99, 66.67, 46.58, 42.56, 31.23. ESI-MS: m/z: 396.21
[MꢃH]-.
CH2N(CH2CH3)2)). 13C NMR (101 MHz, CDCl3)
d 170.21, 151.97,
149.49, 134.20, 133.72, 132.84, 132.78, 126.17, 124.36, 120.17, 118.84,
118.79, 113.27, 111.32, 111.28, 51.31, 47.07, 36.50, 34.24, 11.09. ESI-
MS: m/z: 427.21 [MþH]þ.
5.1.14.20. 1-{[2,5-Bis(4-cyanophenyl)furan-3-yl]acetyl}-4-
methylpiperazine (13t). Light yellow solid (53% yield). 1H NMR
(400 MHz, DMSO)
d 8.05e7.99 (m, 2H, AreH), 7.96e7.87 (m, 6H,
5.1.14.13. N-(2-Piperidin-1-ylethyl)-2-[2,5-bis(4-cyanophenyl)furan-
AreH), 7.27 (s,1H, furaneH), 3.88 (s, 2H, furaneCH2), 3.60e3.53 (m,
2H, piperazineeH), 3.53e3.46 (m, 2H, piperazineeH), 2.35e2.32
(m, 2H, piperazineeH), 2.31e2.25 (m, 2H, piperazineeH), 2.20 (s,
3-yl]acetamide (13m). Light yellow solid (49% yield). 1H NMR
(400 MHz, CDCl3)
d 7.90e7.85 (m, 2H, AreH), 7.82e7.77 (m, 2H,
AreH), 7.75e7.70 (m, 2H, AreH), 7.68 (d, J ¼ 8.4 Hz, 2H, AreH), 7.05
(s, 1H, furaneH), 3.67 (s, 2H, furaneCH2), 3.45e3.40 (m, 2H,
CONHCH2CH2), 2.60e2.58 (m, 2H, CONHCH2CH2), 2.55e2.41 (m,
3H, CH3). 13C NMR (101 MHz, DMSO)
d 167.39, 150.59, 148.40,
133.98, 133.36, 132.94, 132.75, 125.83, 124.26, 121.74, 118.78, 118.75,
114.60, 109.84, 109.74, 54.80, 54.32, 45.61, 45.22, 41.37, 30.48. ESI-