R. Pingaew et al. / Bioorg. Med. Chem. xxx (2015) xxx–xxx
7
CH2Cl2 (2 ꢂ 30 mL). Combined extracts were washed with satu-
rated aqueous NaHCO3, dried (anhyd Na2SO4) and evaporated to
dryness under reduced pressure. The crude product was recrystal-
lized from methanol.
J = 6.0 Hz, 2H, C4-H), 3.42 (t, J = 6.0 Hz, 2H, C3-H), 4.31 (s, 2H, C1-
H), 7.02-7.18 (m, 4H, ArH), 7.22 (d, J = 7.9 Hz, 1H, ArH), 7.47 (s,
1H, ArH), 7.51 (t, J = 7.9 Hz, 1H, ArH), 7.60 (d, J = 7.8 Hz, 1H, ArH).
13C NMR (75 MHz, CDCl3) d 28.7, 43.7, 47.5, 118.0, 123.1, 123.7,
126.3, 126.5, 126.9, 128.8, 130.5, 131.4, 133.0, 138.8, 141.6.
HRMS-TOF: m/z [M+Na]+ 337.0737 (Calcd for C15H14N4NaO2S:
337.0730).
1H NMR of 2-((3-nitrophenyl)sulfonyl)-1,2,3,4-tetrahydroiso-
quinoline (10c) was consistent with that reported in the
literature.19
4.3.1. 6,7-Dimethoxy-2-((3-nitrophenyl)sulfonyl)-1,2,3,4-
tetrahydroisoquinoline (10d)
4.5.2. 2-((3-Azidophenyl)sulfonyl)-6,7-dimethoxy-1,2,3,
4-tetrahydroisoquinoline (12d)
Pale yellow solid. 80%. Mp 133–134 °C. IR (UATR) cmꢁ1: 1611,
1532, 1519, 1351, 1175, 1117. 1H NMR (300 MHz, CDCl3) d 2.86
(t, J = 5.8 Hz, 2H, C4-H), 3.47 (t, J = 5.8 Hz, 2H, C3-H), 3.84 (s, 6H,
2ꢂ OCH3), 4.30 (s, 2H, C1-H), 6.54, 6.55 (2s, 2H, C-5, C-8), 7.76 (t,
J = 8.1 Hz, 1H, ArH), 8.16 (d, J = 7.7 Hz, 1H, ArH), 8.44 (d,
J = 8.0 Hz, 1H, ArH), 8.68 (s, 1H, ArH). 13C NMR (75 MHz, CDCl3) d
28.1, 43.8, 47.2, 55.9, 56.0, 108.9, 111.4, 122.7, 124.6, 127.2,
130.5, 132.9, 139.4, 147.9, 148.1, 148.3. HRMS-TOF: m/z [M+Na]+
401.0768 (Calcd for C17H18N2NaO6S: 401.0778).
Pale yellow solid. 85%. Mp 86–87 °C. IR (UATR) cmꢁ1: 2155,
2106, 1592, 1518, 1465, 1346, 1167, 1116. 1H NMR (300 MHz,
CDCl3) d 2.81 (t, J = 5.8 Hz, 2H, C4-H), 3.37 (t, J = 5.8 Hz, 2H, C3-
H), 3.80 (s, 6H, 2ꢂ OCH3), 4.20 (s, 2H, C1-H), 6.50, 6.53 (s, 2H,
ArH), 7.21 (d, J = 7.7 Hz, 1H, ArH), 7.44 (s, 1H, ArH), 7.48 (t,
J = 7.9 Hz, 1H, ArH), 7.56 (d, J = 7.7 Hz, 1H, ArH). 13C NMR
(75 MHz, CDCl3) d 28.3, 43.8, 47.2, 55.9, 56.0, 109.0, 111.5, 118.0,
123.1, 123.7, 124.9, 130.5, 141.5, 147.9, 148.1. HRMS-TOF: m/z
[M+Na]+ 397.0925 (Calcd for C17H18N4NaO4S: 397.0941).
4.4. General procedure for the synthesis of 1,2,3,4-
tetrahydroisoquinolines (11c–d)
4.6. General procedure for the synthesis of triazoles (32–35)
To a stirred solution of azido 12 (0.2 mmol) and the correspond-
ing alkyne (0.2 mmol) in t-BuOH/H2O (3:3 mL), CuSO4ꢀ5H2O
(0.2 mmol) and ascorbic acid (0.5 mmol) were added. The reaction
mixture was stirred at room temperature for 2–12 h (monitored by
TLC), then concentrated under reduced pressure. The residue was
added water (10 mL) and extracted with dichloromethane
(3 ꢂ 20 mL). The combined organic phases were washed with
water (20 mL), dried over anhyd Na2SO4 and evaporated to dry-
ness. The crude product was purified using silica gel column chro-
matography and eluted with methanol/dichloromethane (1:50).
A mixture of nitroisoquinoline 10 (4 mmol) and SnCl2ꢀ2H2O
(20 mmol) in absolute ethanol (20 mL) was stirred under reflux
for 4 h then concentrated under reduced pressure. Water (20 mL)
was added and extracted with EtOAc (3 ꢂ 20 mL). The organic
extracts were combined and washed with water (20 mL) and brine
(20 mL). The organic layer was dried over anhyd Na2SO4, filtered
and concentrated. The crude product was recrystallized from
methanol.
1H NMR of 2-((3-aminophenyl)sulfonyl)-1,2,3,4-tetrahydroiso-
quinoline (11c) was consistent with that reported in the
literature.19
4.6.1. 7-((1-(3-((3,4-Dihydroisoquinolin-2(1H)-yl)sulfonyl)
phenyl)-1H-1,2,3-triazol-4-yl)methoxy)-2H-chromen-2-one
(32)
4.4.1. 2-((3-Aminophenyl)sulfonyl)-6,7-dimethoxy-1,2,3,4-
tetrahydroisoquinoline (11d)
Pale yellow solid. 80%. Mp 170–171 °C. IR (UATR) cmꢁ1: 3468,
3374, 1626, 1599, 1519, 1317, 1158, 1117. 1H NMR (300 MHz,
DMSO-d6) d 2.76 (t, J = 5.8 Hz, 2H, C4-H), 3.18 (t, J = 5.8 Hz, 2H,
C3-H), 3.64 (s, 6H, 2ꢂ OCH3), 4.00 (s, 2H, C1-H), 5.62 (s, 2H, NH2),
6.67, 6.72 (2s, 2H, C-5, C-8), 6.80 (dd, J = 8.0, 1.3 Hz, 2H, ArH),
6.85 (d, J = 8.0 Hz, 1H, ArH), 6.97 (s, 1H, ArH), 7.22 (t, J = 7.8 Hz,
1H, ArH). 13C NMR (75 MHz, DMSO-d6) d 28.2, 44.2, 47.4, 56.0,
110.0, 110.3, 112.1, 112.3, 114.5, 118.4, 123.7, 125.3, 130.2,
147.8, 148.0, 150.0. HRMS-TOF: m/z [M+Na]+ 371.1039 (Calcd for
White solid. 88%. Mp 180–181 °C. IR (UATR) cmꢁ1: 1725, 1616,
1486, 1342, 1229, 1163, 1127. 1H NMR (300 MHz, CDCl3) d 2.95 (t,
J = 5.9 Hz, 2H, C4-THIQH), 3.50 (t, J = 5.9 Hz, 2H, C3-THIQH), 4.38 (s,
2H, C1-THIQH), 5.39 (s, 2H, CH2O), 6.30 (d, J = 9.5 Hz, 1H, ArH),
6.96–7.02 (m, 2H, ArH), 7.03–7.18 (m, 4H, ArH), 7.44 (d,
J = 9.3 Hz, 1H, ArH), 7.68 (d, J = 9.5 Hz, 1H, ArH), 7.74 (t, J = 8.0 Hz,
1H, ArH), 7.93 (d, J = 8.0 Hz, 1H, ArH), 8.06 (d, J = 8.0 Hz, 1H, ArH),
8.17 (s, 1H, CHN), 8.20 (s, 1H, ArH). 13C NMR (75 MHz, CDCl3) d
28.6, 43.8, 47.5, 62.2, 102.2, 112.7, 113.2, 113.7, 119.3, 121.2,
124.5, 126.3, 126.5, 127.0, 127.6, 128.9, 129.0, 130.9, 131.1,
132.8, 137.4, 139.3, 143.2, 144.4, 155.8, 161.0, 161.1. HRMS-TOF:
m/z [M+H]+ 515.1390 (Calcd for C27H23N4O5S: 515.1384).
C17H20N2NaO4S: 371.1036).
4.5. General procedure for the synthesis of 2-((3-azidophenyl)
sulfonyl)-1,2,3,4-tetrahydroisoquinolines (12c–d)
4.6.2. 4-((1-(3-((3,4-Dihydroisoquinolin-2(1H)-yl)sulfonyl)
phenyl)-1H-1,2,3-triazol-4-yl)methoxy)-2H-chromen-2-one
(33)
To a cold solution of amine 11 (3 mmol) in HCl/CH3COOH
(3:3 mL) at 0 °C, a solution of sodium nitrite (9 mmol) in water
(5 mL) was added. The stirred reaction mixture was maintained
for 15 min and then added dropwise a solution of sodium azide
(9 mmol) in water (5 mL). The reaction mixture was allowed to stir
at room temperature for 0.5 h, then the precipitate was filtered and
washed with cold water. The crude product was recrystallized
from methanol.
White solid. 91%. Mp 168–170 °C. IR (UATR) cmꢁ1: 1712, 1623,
1566, 1494, 1455, 1372, 1336, 1248, 1191, 1153. 1H NMR
(300 MHz, CDCl3) d 2.95 (t, J = 5.9 Hz, 2H, C4-THIQH), 3.51 (t,
J = 5.9 Hz, 2H, C3-THIQH), 4.40 (s, 2H, C1-THIQH), 5.47 (s, 2H,
CH2O), 5.93 (s, 1H, CHCO), 7.04–7.20 (m, 4H, ArH), 7.30 (t,
J = 7.6 Hz, 1H, ArH), 7.35 (d, J = 7.6 Hz, 1H, ArH), 7.59 (dt, J = 7.8,
1.6 Hz, 1H, ArH), 7.76 (t, J = 8.0 Hz, 1H, ArH), 7.85 (dd, J = 7.9,
1.5 Hz, 1H, ArH), 7.95 (d, J = 8.1 Hz, 2H, ArH), 8.08 (d, J = 8.1 Hz,
2H, ArH), 8.22, 8.23 (2s, 2H, ArH, CHN). 13C NMR (75 MHz, CDCl3)
d 28.6, 43.8, 47.5, 62.5, 91.4, 115.4, 116.9, 119.4, 121.6, 123.1,
4.5.1. 2-((3-Azidophenyl)sulfonyl)-1,2,3,4-tetrahydroiso-
quinoline (12c)
Pale yellow solid. 94%. Mp 120–121 °C. IR (UATR) cmꢁ1: 2154,
2109, 1595, 1337, 1169. 1H NMR (300 MHz, CDCl3) d 2.93 (t,