The Journal of Organic Chemistry
Article
General Procedure for the Synthesis of 4-Substituted-
2-(1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)quinoline.
The mixture of 7-azaindole-3-carboxaldehyde 1 (1.0 mmol), amine 2
(1.05 mmol) in acetonitrile, and stannous chloride (0.2 mmol) was
stirred at room temperature for 10 min, and then alkyne 4 (1.5 mmol)
was added to the above mixture. The stirring was then continued at
80 °C for 12 h. The reaction mixture was then quenched with
ammonium chloride solution and extracted with ethyl acetate. The
organic layer was washed with water and brine, dried over sodium
sulfate, and concentrated in vacuum. Crude product was purified by
column chromatography using ethyl acetate−hexane as the solvent to
get quinoline derivative 5.
4-Phenyl-2-(1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-
3-yl)quinoline (5a). Isolated as orange solid: mp 236−239 °C;
1H NMR (400 MHz, CDCl3) δ 7.37 (dd, J = 8.0, 4.8 Hz, 1H, Ar−H),
7.48 (t, J = 8.0 Hz, 2H, Ar−H), 7.48 (s, 1H, Ar−H), 7.53−7.61
(m, 6H, Ar−H), 7.77 (t, J = 7.6 Hz, 1H, Ar−H), 7.77 (s, 1H, Ar−H),
7.92 (d, J = 7.6 Hz, 1H, Ar−H), 8.21 (d, J = 7.2 Hz, 1H, Ar−H), 8.26
(d, J = 7.6 Hz, 2H, Ar−H), 8.37 (bs, 1H, Ar−H), 8.53 (dd, J = 4.8,
1.6 Hz, 1H, Ar−H), 9.15 (d, J = 7.2, Hz, 1H, Ar−H); 13C NMR
(100 MHz, CDCl3) δ 118.9, 119.8, 121.6, 121.9, 125.5, 125.6, 125.8,
126.4, 127.2, 128.1, 128.6, 128.7, 128.9, 129.0, 129.3, 129.5, 129.7,
132.4, 134.2, 137.9, 138.0, 145.6, 147.9, 152.1; UPLC (M + 1) 462.3.
Anal. Calcd for C28H19N3O2S: C, 72.87; H, 4.15; N, 9.10. Found: C,
72.80; H, 4.19; N, 9.18.
6-Methoxy-4-phenyl-2-(1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]-
pyridin-3-yl)quinoline (5b). Isolated as pale yellow solid: mp 222−
224 °C; 1H NMR (400 MHz, CDCl3) δ 3.81 (s, 3H, −OMe), 7.20 (d,
J = 2.8 Hz, 1H, Ar−H), 7.35 (dd, J = 8.0, 4.8 Hz, 1H, Ar−H), 7.40
(dd, J = 9.2, 2.8 Hz, 1H, Ar−H), 7.48 (t, J = 8.0 Hz, 2H, Ar−H),
7.50−7.60 (m, 6H, Ar−H), 7.69 (s, 1H, Ar−H), 8.11 (d, J = 8.8 Hz,
1H, Ar−H), 8.24 (d, J = 8.0 Hz, 2H, Ar−H), 8.30 (s, 1H, Ar−H), 8.52
(d, J = 4.4 Hz, 1H, Ar−H), 9.10 (d, J = 8.0 Hz, 1H, Ar−H); 13C NMR
(100 MHz, CDCl3) δ 55.2, 103.7, 118.69, 119.7, 120.1, 120.9, 121.5,
125.7, 126.9, 127.6, 128.6, 128.7, 129.5, 129.6, 131.1, 132.6, 134.9,
137.4, 137.5, 143.8, 145.3, 146.8, 147.2, 149.9, 157.4; UPLC (M + 1)
492.4. Anal. Calcd for C29H21N3O3S: C, 70.86; H, 4.31; N, 8.55.
Found: C, 70.73; H, 4.26; N, 8.62.
6-Methoxy-4-(2-methoxyphenyl)-2-(1-(phenylsulfonyl)-1H-
pyrrolo[2,3-b]pyridin-3-yl)quinoline (5c). Isolated as orange solid:
mp 211−213 °C; 1H NMR (400 MHz, CDCl3) δ 3.77 (s, 3H,
−OMe), 3.78 (s, 3H, −OMe), 6.88 (d, J = 2.8 Hz, 1H, Ar−H), 7.12
(d, J = 8.4 Hz, 1H, Ar−H), 7.16 (t, J = 7.6 Hz, 1H, Ar−H), 7.32−7.38
(m, 3H, Ar−H), 7.46−7.57 (m, 4H, Ar−H), 7.70 (s, 1H, Ar−H), 8.08
(d, J = 9.2 Hz, 1H, Ar−H), 8.22 (dd, J = 7.2, 1.6 Hz, 2H, Ar−H), 8.27
(s, 1H, Ar−H), 8.51 (dd, J = 4.8, 1.6 Hz, 1H, Ar−H), 9.08 (dd, J =
8.0, 1.6.Hz, 1H, Ar−H); 13C NMR (100 MHz, CDCl3) δ 55.4, 55.5,
104.4, 111.2, 119.6, 120.0, 120.2, 120.9, 121.6, 121.7, 124.7, 126.8,
127.2, 128.0, 129.0, 130.1, 131.0, 131.2, 132.3, 134.1, 138.2, 144.4,
145.1, 145.5, 147.9, 149.7, 156.7, 157.6; UPLC (M + 1) 522.4. Anal.
Calcd for C30H23N3O4S: C, 69.08; H, 4.44; N, 8.06. Found: C, 69.01;
H, 4.48; N, 8.02.
4.8 Hz, 1H, Ar−H), 7.61−7.64 (m, 4H, Ar−H), 7.72 (t, J = 7.6 Hz,
1H, Ar−H), 8.08 (d, J = 8.8 Hz, 1H, Ar−H), 8.18 (d, J = 8.0 Hz, 2H,
Ar−H), 8.20 (s, 1H, Ar−H), 8.46 (d, J = 4.8 Hz, 1H, Ar−H), 9.03
(s, 1H, Ar−H), 9.25 (dd, J = 8.0, 0.8 Hz, 1H, Ar−H), 9.73 (s, 1H,
−OH); 13C NMR (100 MHz, DMSO-d6) δ 21.4, 115.4, 116.4, 118.6,
119.1, 120.1, 120.3, 120.9, 124.1, 124.8, 127.3, 127.6, 129.3, 129.6,
129.7, 131.7, 132.6, 134.8, 136.0, 137.4, 138.7, 145.3, 146.4, 147.2,
147.7, 151.4, 157.5; UPLC (M + 1) 492.3. Anal. Calcd for
C29H21N3O3S: C, 70.86; H, 4.31; N, 8.55. Found: C, 70.75; H, 4.27;
N, 8.62.
4-(4-Ethylphenyl)-2-(1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]-
pyridin-3-yl)-6-(trifluoromethyl)quinoline (5f). Isolated as orange
1
solid: mp 212−214; °C H NMR (400 MHz, CDCl3) δ 1.38 (t, J =
7.6 Hz, 3H, −CH3), 2.83 (q, J = 7.6 Hz, 2H, −CH2), 7.38 (dd, J =
8.0, 4.8 Hz, 1H, Ar−H), 7.44−7.53 (m, 6H, Ar−H), 7.60 (t, J =
7.6 Hz, 1H, Ar−H), 7.83 (s, 1H, Ar−H), 7.91 (d, J = 8.8 Hz, 1H,
Ar−H), 8.26−8.32 (m, 4H, Ar−H), 8.43 (s, 1H, Ar−H), 8.54 (d, J =
8.4 Hz, 1H, Ar−H), 9.13 (d, J = 8.0 Hz, 1H, Ar−H); 13C NMR (100
MHz, CDCl3) δ 15.5, 28.7, 119.9, 120.9, 121.3, 123.8, 123.9, 124.8,
125.4, 125.5, 126.2, 127.8, 128.1, 128.2, 128.5, 129.1, 129.4, 130.7,
132.4, 134.2, 134.3, 137.9, 145.5, 145.8, 147.8, 149.9, 154.2; UPLC
(M + 1) 558.3. Anal. Calcd for C31H22F3N3O2S: C, 66.78; H, 3.98; N,
7.54. Found: C, 66.81; H, 4.02; N, 7.59.
4-(Biphenyl-4-yl)-2-(1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]-
pyridin-3-yl)-6-(trifluoromethyl)quinoline (5g). Isolated as pale
yellow solid: mp 195−197 °C; 1H NMR (400 MHz, CDCl3) δ 7.39−
7.56 (m, 6H, Ar−H), 7.61 (t, J = 7.6 Hz, 1H, Ar−H), 7.68 (d, J =
8.0 Hz, 2H, Ar−H), 7.75 (d, J = 9.2 Hz, 2H, Ar−H), 7.87 (dd, J = 6.4,
1.6 Hz, 2H, Ar−H),7.89 (s, 1H, Ar−H), 7.93 (dd, J = 8.8, 2.0 Hz, 1H,
Ar−H), 8.27−8.30 (m, 2H, Ar−H), 8.33 (d, J = 8.8 Hz, 1H, Ar−H),
8.46 (s, 1H, Ar−H), 8.55 (dd, J = 4.8, 1.6 Hz, 2H, Ar−H), 9.16
(dd, J = 8.0, 1.6 Hz, 1H, Ar−H); 13C NMR (100 MHz, CDCl3)
δ 118.9, 119.8, 119.9, 121.4, 122.6, 123.7, 123.8, 124.7, 125.4, 126.2,
127.2, 127.7, 127.9, 128.2, 129.0, 129.1, 129.9, 130.8, 132.4, 134.3,
135.8, 137.9, 140.2, 142.1, 145.8, 147.8, 149.6, 149.8, 154.2; UPLC
(M + 1) 606.3. Anal. Calcd for C35H22F3N3O2S: C, 69.41; H, 3.66; N,
6.94. Found: C, 69.37; H, 3.69; N, 6.87.
6-Nitro-4-phenyl-2-(1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]-
pyridin-3-yl)quinoline (5h). Isolated as orange solid: mp 228−
230 °C; 1H NMR (400 MHz, CDCl3) δ 7.40 (dd, J = 8.0, 4,8 Hz, 1H, Ar−
H), 7.52 (t, J = 8.0 Hz, 2H, Ar−H), 7.58−7.67 (m, 6H, Ar−H), 7.89
(s, 1H, Ar−H), 8.27−8.31 (m, 3H, Ar−H), 8.48 (s, 1H, Ar−H), 8.49
(dd, J = 7.6, 2.4 Hz, 1H, Ar−H), 8.55 (dd, J = 8.4, 0.8 Hz, 1H, Ar−H),
8.84 (d, J = 2.4 Hz, 1H, Ar−H), 9.15 (dd, J = 8.4, 0.8 Hz, 1H, Ar−H);
13C NMR (100 MHz, CDCl3) δ 118.6, 120.0, 120.3, 121.2, 122.9,
123.3, 124.6, 126.9, 128.3, 129.2, 129.3, 129.4, 129.6, 131.2, 132.4,
134.5, 136.5, 137.8, 145.4, 146.0, 147.8, 150.9, 151.0, 155.5; UPLC
(M + 1) 507.4. Anal. Calcd for C28H18N4O4S: C, 66.39; H, 3.58; N,
11.06. Found: C, 66.29; H, 3.52; N, 11.10.
4-(2-Methoxyphenyl)-6-nitro-2-(1-(phenylsulfonyl)-1H-
pyrrolo[2,3-b]pyridin-3-yl)quinoline (5i). Isolated as orange solid:
1
mp 237−239 °C; H NMR (400 MHz, DMSO-d6) δ 3.72 (s, 3H,
−OCH3), 7.25 (t, J = 7.6 Hz, 1H, Ar−H), 7.34 (d, J = 8.4 Hz, 1H, Ar−
H), 7.49−7.52 (m, 2H, Ar−H), 7.65 (t, J = 7.6 Hz, 3H, Ar−H), 7.75
(t, J = 7.6 Hz, 1H, Ar−H), 8.21 (d, J = 7.2 Hz, 2H, Ar−H), 8.31
(s, 1H, Ar−H), 8.35 (d, J = 9.2 Hz, 1H, Ar−H), 8.45−8.50 (m, 3H,
Ar−H), 9.20 (s, 1H, Ar−H), 9.27 (d, J = 7.6 Hz, 1H, Ar−H); 13C
NMR (100 MHz, DMSO-d6) δ 56.1, 112.3, 118.4, 120.8, 121.1, 121.5,
122.2, 123.1, 123.4, 125.0, 125.2, 128.2, 129.8, 130.2, 131.5, 131.6,
131.8, 133.2, 135.5, 137.7, 145.0, 146.1, 147.7, 148.4, 150.2, 156.5,
156.7; UPLC (M + 1) 537.4. Anal. Calcd for C29H20N4O5S: C, 64.92;
H, 3.76; N, 10.44. Found: C, 64.87; H, 3.72; N, 10.38.
4-Cyclohexenyl-6-methoxy-2-(1-(phenylsulfonyl)-1H-
pyrrolo[2,3-b]pyridin-3-yl)quinoline (5d). Isolated as orange
1
solid: mp 231−233; °C H NMR (400 MHz, CDCl3) δ 1.83−1.87
(m, 2H), 1.89−1.94 (m, 2H), 2.34−2.35 (m, 2H), 2.45−2.46 (m, 2H),
3.94 (s, 3H, −OMe), 5.93 (bs, 1H, −CH), 7.27−7.39 (m, 3H, Ar−H),
7.49 (t, J = 8.0 Hz, 2H, Ar−H),7.56−7.60 (m, 2H, Ar−H), 8.05
(bs, 1H, Ar−H), 8.25−8.31 (m, 3H, Ar−H), 8.51 (dd, J = 4.8, 1.6 Hz,
1H, Ar−H), 9.05 (bs, 1H, Ar−H); 13C NMR (100 MHz, CDCl3) δ
22.1, 23.0, 25.5, 30.1, 55.5, 104.0, 117.5, 119.7, 119.9, 121.4, 121.7,
124.7, 126.5, 128.0, 128.8, 129.0, 131.1, 132.3, 134.2, 135.8, 138.2,
144.5, 145.5, 147.9, 149.9, 150.7, 157.5; UPLC (M + 1) 496.4. Anal.
Calcd for C29H25N3O3S: C, 70.28; H, 5.08; N, 8.48. Found: C, 70.24;
H, 5.05; N, 8.52.
4-Phenyl-2-(1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-3-
yl)quinoline-6-carbonitrile (5j). Isolated as off white solid: mp
236−238 °C; 1H NMR (400 MHz, CDCl3) δ 7.38 (dd, J = 8.0, 4.8 Hz,
1H, Ar−H), 7.49−7.56 (m, 4H, Ar−H), 7.59−7.65 (m, 4H, Ar−H),
7.86−7.89 (m, 2H, Ar−H), 8.27−8.29 (m, 4H, Ar−H), 8.46 (s, 1H,
Ar−H), 8.55 (dd, J = 4.4, 1.2 Hz, 1H, Ar−H), 9.13 (dd, J = 8.0, 1.2 Hz,
1H, Ar−H); 13C NMR (100 MHz, CDCl3) δ 109.7, 118.6, 118.9,
120.0, 120.2, 121.2, 125.2, 126.7, 128.3, 129.2, 129.3, 129.4, 129.5,
3-(6-Methyl-2-(1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-
3-yl)quinolin-4-yl)phenol (5e). Isolated as orange solid: mp 214−
216 °C; 1H NMR (400 MHz, DMSO-d6) δ 2.44 (s, 3H, −CH3), 6.95
(dd, J = 8.0, 2.0 Hz, 1H, Ar−H), 6.99 (s, 1H, Ar−H), 7.03 (d, J =
7.6 Hz, 1H, Ar−H), 7.40 (t, J = 8.0 Hz, 1H, Ar−H), 7.47 (dd, J = 8.0,
1473
dx.doi.org/10.1021/jo202256z | J. Org. Chem. 2012, 77, 1468−1476