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7.03 (d, 2H, J = 8.5 Hz, aromatic H), 4.02 (t, 4H, J = 6.5 Hz, pyrroli-
dine H), 3.91 (s, 3H, OCH3), 2.06 (t, 4H, J = 6.5 Hz, pyrrolidine H).
ESI-MS (m/z): 370 [M+1]+.
H), 4.92 (s, 2H, hydroisoquinoline H), 4.12 (t, 2H, J = 6.0 Hz, hydro-
isoquinoline H), 3.24 (t, 2H, J = 6.0 Hz, hydroisoquinoline H). ESI-
MS (m/z): 482 [M+1]+.
5.1.1.4. 2-Pyrrolidinyl-3-(4-bromophenylsulfonyl)quinoxaline
(7d).
5.1.2.5. 2-(3,4-Dihydroisoquinolin-2(1H)-yl)-3-(4-fluorophenyl-
sulfonyl)quinoxaline (8e).
Yield: 76%, mp: 134–136 °C. 1H NMR (500 MHz, CDCl3):
Yield: 79%, mp: 171–175 °C. 1H
d 7.83 (d, 2H, J = 8.5 Hz, aromatic H), 7.70 (d, 2H, J = 8.5 Hz,
aromatic H), 7.66 (d, 1H, J = 8.5 Hz, aromatic H), 7.59–7.55 (m,
1H, aromatic H), 7.40 (d, 1H, J = 8.0 Hz, aromatic H), 7.25 (d, 1H,
J = 8.0 Hz, aromatic H), 4.01 (t, 4H, J = 6.5 Hz, pyrrolidine H), 2.07
(t, 4H, J = 6.5 Hz, pyrrolidine H). ESI-MS (m/z): 420 [M+1]+.
NMR (500 MHz, CDCl3): d 8.02–7.99 (m, 2H, aromatic H), 7.80 (d,
1H, J = 8.5 Hz, aromatic H), 7.68 (t, 1H, J = 7.5 Hz, aromatic H),
7.61 (d, 1H, J = 8.0 Hz, aromatic H), 7.44 (t, 1H, J = 7.5 Hz, aromatic
H), 7.71–7.16 (m, 6H, aromatic H), 4.92 (s, 2H, hydroisoquinoline
H), 4.12 (t, 2H, J = 5.5 Hz, hydroisoquinoline H), 3.25 (t, 2H,
J = 5.5 Hz, hydroisoquinoline H). ESI-MS (m/z): 420 [M+1]+.
5.1.1.5. 2-Pyrrolidinyl-3-(4-fluorophenylsulfonyl)quinoxaline
(7e).
Yield: 71%, mp: 94–97 °C. 1H NMR (500 MHz, CDCl3): d
5.1.3. General procedure for the synthesis of 2-(piperidin-3-ol)-
3-(arylsulfonyl)quinoxalines (9)
7.98–7.97 (m, 2H, aromatic H), 7.65 (d, 1H, J = 7.5 Hz, aromatic
H), 7.58 (d, 1H, J = 6.5 Hz, aromatic H), 7.38 (d, 1H, J = 7.5 Hz, aro-
matic H), 7.24–7.23 (m, 3H, aromatic H), 4.00 (m, 4H, pyrrolidine
H), 2.06 (m, 4H, pyrrolidine H). ESI-MS (m/z): 358 [M+1]+.
To a microwave vial (2–5 mL) were added 2-choloro-3-(aryl-
sulfonyl)quinoxaline
6
(0.1 mmol), piperidin-3-ol (30 mg,
0.3 mmol), and isopropyl alcohol (2 mL). The sealed vial was
heated at 80 °C for 10 min by microwave irradiation in a Biotage™
Initiator Synthesizer using a fixed hold time. The mixture was then
cooled to room temperature and the residue obtained after evapo-
rating under vacuum was subjected to purification over silica gel
chromatography eluting with PE/EtOAc (3:1, v/v) to afford target
compounds 9 as yellow solid.
5.1.2. General procedure for the synthesis of 2-(3,4-dihydro-
isoquinolin-2(1H)-yl)-3-(arylsulfonyl)quinoxalines (8)
To a microwave vial (2–5 mL) were added 2-choloro-3-(aryl-
sulfonyl)quinoxaline 6 (0.1 mmol), 1,2,3,4-tetrahydroisoquinoline
(40 mg, 0.3 mmol), and isopropyl alcohol (2 mL). The sealed vial
was heated at 80 °C for 10 min by microwave irradiation in a Bio-
tage™ Initiator Synthesizer using a fixed hold time. The mixture
was then cooled to room temperature and the residue obtained
after evaporating under vacuum was subjected to purification over
silica gel chromatography eluting with PE/EtOAc (8:1, v/v) to afford
target compounds 8 as yellow solid.
5.1.3.1. 2-(Piperidin-3-ol)-3-(phenylsulfonyl)quinoxaline (9a).
Yield: 42%, mp: 118–120 °C. 1H NMR (500 MHz, CDCl3): d 8.01
(d, 2H, J = 7.5 Hz, aromatic H), 7.79 (d, 1H, J = 7.5 Hz, aromatic H),
7.70–7.64 (m, 3H, aromatic H), 7.56–7.55 (m, 2H, aromatic H),
7.48–7.46 (m, 1H, aromatic H), 4.14 (m, 1H, piperidine H), 3.90–
3.89 (m, 2H, piperidine H), 3.68 (br s, 1H, hydroxy H), 3.61–3.58
(d, 1H, J = 13.0 Hz, piperidine H), 3.52 (t, 1H, J = 10.0 Hz,
piperidine H), 2.16–2.15 (m, 1H, piperidine H), 1.87–1.82 (m, 2H,
piperidine H), 1.73–1.71 (m, 1H, piperidine H). ESI-MS (m/z): 370
[M+1]+.
5.1.2.1.
nyl)quinoxaline (8a).
2-(3,4-Dihydroisoquinolin-2(1H)-yl)-3-(phenylsulfo-
Yield: 69%, mp: 149–150 °C. 1H NMR
(500 MHz, CDCl3): d 7.99 (d, 2H, J = 7.5 Hz, aromatic H), 7.79 (d,
1H, J = 8.5 Hz, aromatic H), 7.67 (t, 1H, J = 6.0 Hz, aromatic H),
7.62 (t, 2H, J = 8.0 Hz, aromatic H), 7.52 (t, 2H, J = 8.0 Hz, aromatic
H), 7.42 (t, 1H, J = 7.5 Hz, aromatic H), 7.23–7.21 (m, 4H, aromatic
H), 4.92 (s, 2H, hydroisoquinoline H), 4.13 (t, 2H, J = 5.5 Hz, hydro-
isoquinoline H), 3.25 (t, 2H, J = 5.5 Hz, hydroisoquinoline H). ESI-
MS (m/z): 402 [M+1]+.
5.1.3.2. 2-(Piperidin-3-ol)-3-(4-methylphenylsulfonyl)quinoxa-
line (9b).
CDCl3):
Yield: 45%, mp: 139–142 °C. 1H NMR (500 MHz,
7.90 (d, 2H, J = 8.5 Hz, aromatic H), 7.79 (d, 1H,
d
J = 8.5 Hz, aromatic H), 7.70–7.67 (m, 2H, aromatic H), 7.49 (t,
1H, J = 8.0 Hz, aromatic H), 7.34 (d, 2H, J = 8.5 Hz, aromatic H),
4.14–4.13 (m, 1H, piperidine H), 3.93–3.91 (m, 2H, piperidine H),
3.69 (br s, 1H, hydroxy H), 3.57 (d, 1H, J = 13.5 Hz, aromatic H),
3.49 (dt, 1H, J = 10.0 and 2.5 Hz, piperidine H), 2.46 (s, 3H, CH3),
2.19–2.12 (m, 1H, piperidine H), 1.91–1.87 (m, 1H, piperidine H),
1.83–1.78 (m, 1H, piperidine H), 1.72–1.69 (m, 1H, piperidine H).
ESI-MS (m/z): 384 [M+1]+.
5.1.2.2.
2-(3,4-Dihydroisoquinolin-2(1H)-yl)-3-(4-methyl-
Yield: 63%, mp: 170–
phenylsulfonyl)quinoxaline (8b).
172 °C. 1H NMR (500 MHz, CDCl3): d 7.87 (d, 2H, J = 8.0 Hz,
aromatic H), 7.79 (d, 1H, J = 8.5 Hz, aromatic H), 7.66–7.62 (m,
2H, aromatic H), 7.42 (t, 1H, J = 8.5 Hz, aromatic H), 7.29 (d, 2H,
J = 8.0 Hz, aromatic H), 7.23–7.20 (m, 4H, aromatic H), 4.91 (s,
2H, hydroisoquinoline H), 4.12 (t, 2H, J = 6.0 Hz, hydroisoquinoline
H), 3.25 (t, 2H, J = 6.0 Hz, hydroisoquinoline H), 2.43 (s, 3H, CH3).
ESI-MS (m/z): 416 [M+1]+.
5.1.3.3. 2-(Piperidin-3-ol)-3-(4-methoxyphenylsulfonyl)quinox-
aline (9c).
Yield: 50%, mp: 91–94 °C. 1H NMR (500 MHz,
CDCl3): d 7.96 (d, 2H, J = 8.5 Hz, aromatic H), 7.78 (dd, 1H, J = 9.0
and 1.5 Hz, aromatic H), 7.69–7.66 (m, 2H, aromatic H), 7.49 (dt,
1H, J = 8.5 and 1.5 Hz, aromatic H), 7.00 (d, 2H, J = 8.5 Hz, aromatic
H), 4.14–4.13 (m, 1H, piperidine H), 3.92 -3.90 (m, 2H, piperidine
H), 3.88 (s, 1H, OCH3), 3.79 (br s, 1H, hydroxy H), 3.56 (dd, 1H,
J = 13.0 and 1.5 Hz, aromatic H), 3.48 (dt, 1H, J = 10.0 and 2.5 Hz,
piperidine H), 2.17–2.11 (m, 1H, piperidine H), 1.90–1.87 (m, 1H,
piperidine H), 1.83–1.76 (m, 1H, piperidine H), 1.72–1.68 (m, 1H,
piperidine H). ESI-MS (m/z): 400 [M+1]+.
5.1.2.3.
2-(3,4-Dihydroisoquinolin-2(1H)-yl)-3-(4-methoxy-
Yield: 58%, mp: 148–
phenylsulfonyl)quinoxaline (8c).
150 °C. 1H NMR (500 MHz, CDCl3): d 7.93 (d, 2H, J = 9.0 Hz,
aromatic H), 7.79 (d, 1H, J = 9.0 Hz, aromatic H), 7.65 (d, 1H,
J = 8.0 Hz, aromatic H), 7.43 (dt, 1H, J = 8.0 and 1.5 Hz, aromatic
H), 7.28–7.18 (m, 4H, aromatic H), 6.96 (d, 2H, J = 9.0 Hz, aromatic
H), 4.91 (s, 2H, hydroisoquinoline), 4.11 (t, 2H, J = 6.0 Hz, hydroiso-
quinoline H), 3.87 (s, 3H, methoxy H), 3.25 (t, 2H, J = 6.0 Hz, hydro-
isoquinoline H). ESI-MS (m/z): 432 [M+1]+.
5.1.3.4. 2-(Piperidin-3-ol)-3-(4-bromophenylsulfonyl)quinoxa-
5.1.2.4. 2-(3,4-Dihydroisoquinolin-2(1H)-yl)-3-(4-bromophenyl-
sulfonyl)quinoxaline (8d).
line (9d).
CDCl3):
Yield: 57%, mp: 108–112 °C. 1H NMR (500 MHz,
d 7.87 (d, 2H, J = 8.5 Hz, aromatic H), 7.76 (d, 1H,
Yield: 59%, mp: 184–185 °C. 1H
NMR (500 MHz, CDCl3): d 7.85 (d, 2H, J = 8.5 Hz, aromatic H),
7.79 (d, 1H, J = 8.0 Hz, aromatic H), 7.69–7.60 (m, 4H, aromatic
H), 7.44 (t, 1H, J = 8.0 Hz, aromatic H), 7.22–7.20 (m, 4H, aromatic
J = 8.5 Hz, aromatic H), 7.69–7.66 (m, 3H, aromatic H), 7.64 (d,
1H, J = 8.5 Hz, aromatic H), 7.46 (t, 1H, J = 8.0 Hz, aromatic H),
4.11–4.08 (m, 2H, piperidine H), 4.03–4.00 (m, 1H, piperidine H),