Month 2019
Synthesis of Imidazo[1,2-a]pyridines and Imidazo[2,1-b]thiazoles Attached to a
Cycloalkyl or Saturated Heterocycle Containing a Tertiary Hydroxy Substitution
2-(1-Hydroxycyclohexyl)imidazo[1,2-a]pyridine-6-
2H), 1.87–1.78 (m, 2H), 1.67–1.57 (m, 3H), 1.46–1.36
(m, 1H); 13C NMR (100 MHz, CDCl3): δ 153.40,
143.27, 132.70, 129.11, 128.74, 126.06, 124.54, 123.27,
116.94, 115.04, 105.98, 70.69, 38.12, 25.58, 22.18;
HRMS (ESI) m/z calcd for C17H18N2O [M + Na]+,
289.1317; found 289.1315.
carbonitrile (8d). Off white solid (95 mg, 94% yield); m.
1
p.: 200.2–201.4 °C; H NMR (400 MHz, DMSO-d6): δ
9.27 (s, 1H), 7.83 (s, 1H), 7.62 (d, J = 9.6 Hz, 1H), 7.40
(d, J = 9.2 Hz, 1H), 4.86 (s, 1H), 1.93–1.86 (m, 2H),
1.72–1.56 (m, 5H), 1.47–1.44 (m, 2H), 1.29–1.21 (m,
1H); 13C NMR (100 MHz, DMSO-d6): δ 158.50, 143.60,
134.50, 124.24, 117.77, 117.72, 110.24, 96.72, 70.12,
37.82, 25.72, 21.92; HRMS (ESI) m/z calcd for
C14H15N3O [M + Na]+, 264.1113; found 264.1114.
1-(Imidazo[2,1-a]isoquinolin-2-yl)cyclohexanol (8j).
Off
white solid (84 mg, 92% yield); m.p.: 149.5–150.3 °C;
1H NMR (400 MHz, CDCl3): δ 8.61 (d, J = 8.0 Hz, 1H),
7.85 (d, J = 7.6 Hz, 1H), 7.68 (d, J = 8.0 Hz, 1H), 7.68
(d, J = 8.0 Hz, 1H), 7.60 (t, J = 7.6 Hz, 1H), 7.54 (t,
J = 7.4 Hz, 1H), 7.42 (s, 1H), 7.01 (d, J = 7.2 Hz, 1H),
2.96 (bs, 1H), 2.04–1.97 (m, 5H), 1.88–1.79 (m, 2H),
1.65–1.60 (m, 2H), 1.43–1.33 (m, 1H); 13C NMR
(100 MHz, CDCl3): δ 152.34, 142.22, 129.38, 127.98,
126.81, 123.78, 123.42, 123.05, 112.85, 108.76, 70.33,
38.36, 25.65, 22.25; HRMS (ESI) m/z calcd for
C17H18N2O [M + H]+, 267.1497; found 267.1495.
Methyl
2-(1-hydroxycyclohexyl)imidazo[1,2-a]pyridine-6-
carboxylate (8e). Pale yellow solid (79 mg, 88% yield);
1
m.p.: 203.5–203.9 °C; H NMR (400 MHz, CDCl3): δ
8.86 (s, 1H), 7.77 (d, J = 8.8 Hz, 1H), 7.57–7.51 (m,
2H), 3.94 (s, 3H), 2.49 (s, 1H), 2.00–1.96 (m, 2H), 1.92–
1.88 (m, 2H), 1.64–1.59 (m, 2H), 1.42–1.36 (m, 1H); 13C
NMR (100 MHz, CDCl3): δ 165.33, 156.56, 145.32,
129.99, 124.06, 116.62, 116.29, 108.43, 70.68, 52.37,
37.92, 25.46, 21.99; HRMS (ESI) m/z calcd for
C15H18N2O3 [M + Na]+, 297.1215; found 297.1207.
1-(6-Nitroimidazo[1,2-a]pyridin-2-yl)cyclohexanol (8f).
Pale yellow solid (73 mg, 78% yield); m.p.: 238.2–239.5
1-(Imidazo[1,2-a]pyridin-2-yl)cyclopentanol (8k).
Pale
yellow solid (90 mg, 84% yield); m.p.: 150.1–151.4 °C;
1H NMR (400 MHz, CDCl3): δ 8.06 (d, J = 6.8 Hz, 1H),
7.55 (d, J = 8.8 Hz, 1H), 7.51 (s, 1H), 7.15 (t,
J = 8.0 Hz, 1H), 6.75 (t, J = 7.0 Hz, 1H), 2.60 (bs, 1H),
2.20–2.15 (m, 2H), 2.04–1.97 (m, 4H), 1.89–1.82 (m,
2H); 13C NMR (100 MHz, CDCl3): δ 152.99, 144.96,
125.65, 124.53, 117.25, 112.20, 107.41, 80.39, 41.31,
23.93; LCMS (ESI) m/z calcd for C12H14N2O [M + Na]+,
1
°C; H NMR (400 MHz, DMSO-d6): δ 9.84 (s, 1H), 8.01
(s, 1H), 7.86 (d, J = 9.6 Hz, 1H), 7.61 (d, J = 9.6 Hz,
1H), 4.96 (s, 1H), 1.98–1.86 (m, 2H), 1.69–1.57 (m, 5H),
1.48–1.45 (m, 2H), 1.26–1.21 (m, 1H); 13C NMR
(100 MHz, DMSO-d6): δ 159.80, 144.43, 136.53, 128.48,
118.46, 116.26, 111.75, 70.21, 37.74, 25.70, 21.87;
HRMS (ESI) m/z calcd for C13H15N3O3 [M + Na]+,
225.1004; found 225.1008.
1-(6-Methylimidazo[1,2-a]pyridin-2-yl)cyclopentanol (8l).
Pale yellow solid (85 mg, 85% yield); m.p.: 147.8–
284.1011; found 284.1012.
1
1-(6-Methoxyimidazo[1,2-a]pyridin-2-yl)cyclohexanol
(8g). Pale brown solid (90 mg, 91% yield); m.p.: 150.3–
148.5 °C; H NMR (400 MHz, CDCl3): δ 7.84 (s, 1H),
7.44 (d, J = 9.2 Hz, 1H), 7.41 (s, 1H), 6.99 (d,
J = 9.2 Hz, 1H), 2.29 (s, 1H), 2.19–2.09 (m, 2H),
2.05–1.99 (m, 4H), 1.84–1.79 (m, 2H); 13C NMR
(100 MHz, CDCl3): δ 152.71, 144.00, 127.62, 123.73,
121.71, 116.50, 107.11, 80.34, 41.23, 23.91, 18.00;
HRMS (ESI) m/z calcd for C13H16N2O [M + Na]+,
239.1160; found 239.1162.
1
151.8 °C; H NMR (400 MHz, CDCl3): δ 7.60 (s, 1H),
7.44 (d, J = 7.6 Hz, 2H), 6.94 (d, J = 9.6 Hz, 1H), 3.81
(s, 3H), 2.57 (bs, 1H), 1.97–1.92 (m, 4H), 1.87–1.78 (m,
3H), 1.38–1.35 (m, 3H); 13C NMR (100 MHz, CDCl3): δ
154.20, 149.18, 141.71, 119.70, 117.41, 108.45, 107.66,
70.53, 56.19, 38.12, 25.56, 22.15; HRMS (ESI) m/z calcd
for C14H18N2O2 [M + Na]+, 269.1266; found 269.1263.
1-(Imidazo[1,2-a]pyridin-2-yl)cycloheptanol (8m).
Pale
1-(6-Bromoimidazo[1,2-a]pyridin-2-yl)cyclohexanol (8h).
yellow solid (110 mg, 90% yield); m.p.: 141.3–142.6 °C;
1H NMR (400 MHz, CDCl3): δ 8.06 (d, J = 6.8 Hz, 1H),
7.55 (d, J = 9.2 Hz, 1H), 7.47 (s, 1H), 7.14 (t,
J = 8.0 Hz, 1H), 6.75 (t, J = 6.4 Hz, 1H), 2.82 (bs, 1H),
2.19–2.13 (m, 2H), 2.10–2.04 (m, 2H), 1.85–1.77 (m,
2H), 1.73–1.68 (m, 2H), 1.67–1.58 (m, 4H); 13C NMR
(100 MHz, CDCl3): δ 155.50, 144.73, 125.68, 124.37,
117.38, 112.11, 106.99, 74.23, 41.94, 29.48, 22.26;
HRMS (ESI) m/z calcd for C14H18N2O [M + Na]+,
253.1317; found 253.1317.
Pale brown solid (75 mg, 83% yield); m.p.: 195.7–196.3
1
°C; H NMR (400 MHz, CDCl3): δ 8.22 (s, 1H), 7.47 (s,
1H), 7.45 (d, J = 10.4 Hz, 1H), 7.21 (dd, J = 1.6 Hz,
J = 1.6 Hz, 1H), 2.51 (s, 1H), 2.01–1.73 (m, 7H), 1.70–
1.58 (m, 2H), 1.41–1.28 (m, 1H); 13C NMR (100 MHz,
CDCl3): δ 155.41, 143.17, 127.93, 125.75, 117.97,
107.71, 106.76, 70.61, 38.03, 25.47, 22.02; HRMS (ESI)
m/z calcd for C13H15BrN2O [M + Na]+, 317.0265,
319.0245; found 317.0264, 318.9096.
1-(Imidazo[1,2-a]quinolin-2-yl)cyclohexanol (8i).
Pale
1-(Imidazo[1,2-a]pyrimidin-2-yl)cycloheptanol (8n).
Pale
brown solid (85 mg, 93% yield); m.p.: 182.1–183.3 °C;
1H NMR (400 MHz, CDCl3): δ 7.96 (s, 1H), 7.47 (s,
1H), 7.89 (d, J = 8.4 Hz, 1H), 7.80 (d, J = 8.0 Hz, 1H),
7.63 (t, J = 7.8 Hz, 1H), 7.54–7.48 (m, 2H), 7.46–7.43
(m, 1H), 2.57 (bs, 1H), 2.10–2.04 (m, 2H), 1.98–1.94 (m,
yellow solid (54 mg, 45% yield); m.p.: 151.5–152.4 °C;
1H NMR (400 MHz, CDCl3): δ 8.51 (d, J = 1.6 Hz, 1H),
8.38 (d, J = 6.0 Hz, 1H), 7.44 (s, 1H), 6.86–6.83 (m,
1H), 3.64 (bs, 1H), 2.20–2.14 (m, 2H), 2.09–2.04 (m,
2H), 1.79–1.61 (m, 8H); 13C NMR (100 MHz, CDCl3): δ
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet