10.1002/adsc.202000040
Advanced Synthesis & Catalysis
131.8, 131.4, 128.8, 128.5, 128.4, 128.0, 126.1, 126.0,
125.7, 125.6, 125.3, 124.5, 121.7, 121.7, 120.1, 119.9,
115.8, 115.7, 75.9, 75.0, 67.4, 67.3, 48.0, 47.8, 47.6, 47.3,
31.5, 31.3, 30.0, 29.6, 25.6, 25.3. HRMS (ESI), m/z calcd.
for C21H20BrN2O2 ([M+H]+) 411.0703, found: 411.0699.
122.1, 121.3, 119.9, 119.8, 115.7, 115.6, 75.8, 75.0, 67.4,
67.3, 48.1, 47.9, 47.5, 31.5, 31.3, 30.0, 29.6, 25.7, 25.3.
HRMS (ESI), m/z calcd. for C21H20ClN2O2 ([M+H]+)
367.1208, found: 367.1201.
3-bromo-5-methyl-5-((tetrahydrofuran-2-
3,5-dimethyl-5-((tetrahydrofuran-2-
yl)methyl)benzo[4,5]imidazo[2,1-a]isoquinolin-6(5H)-
one (3l). Flash column chromatography (petroleum
ether/ethyl acetate = 10:1) gave 79 mg of product as a
yellow solid in 64% yield; mp: 121-122 oC; 1H NMR (400
MHz, CDCl3) δ 8.41-8.28 (m, 2H), 7.85-7.76 (m, 1H),
7.68-7.56 (m, 2H), 7.49-7.36 (m, 2H), 3.57-3.45 (m, 1H),
3.45-3.29 (m, 1.5H), 3.18 (dd, J = 15.2, 7.2 Hz, 0.5H),
2.72 (dd, J = 14.0, 11.6 Hz, 0.5H), 2.57 (dd, J = 14.4, 6.4
Hz, 0.5H), 2.37 (dd, J = 14.0, 6.4 Hz, 0.5H), 2.12 (dd, J =
yl)methyl)benzo[4,5]imidazo[2,1-a]isoquinolin-6(5H)-
one (3h). Flash column chromatography (petroleum
ether/ethyl acetate = 10:1) gave 78 mg of product as a
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white solid in 75% yield; mp: 130-131 C; H NMR (400
MHz, CDCl3) δ 8.47-8.28 (m, 2H), 7.86-7.73 (m, 1H),
7.49-7.37 (m, 2H), 7.35-7.22 (m, 2H), 3.56-3.34 (m, 2.5H),
3.20 (dd, J = 14.8, 7.2 Hz, 0.5H), 2.71 (dd, J = 14.0, 11.2
Hz, 0.5H), 2.59 (dd, J = 13.6, 8.0 Hz, 0.5H), 2.53-2.40 (m,
3.5H), 2.16 (dd, J = 14.0, 3.6 Hz, 0.5H), 1.88-1.73 (m, 3H), 14.4, 3.6 Hz, 0.5H), 1.88-1.71 (m, 3H), 1.71-1.43 (m, 3H),
1.72-1.60 (m, 2H), 1.59-1.38 (m, 1H), 1.36-1.10 (m, 1H).
13C NMR (100 MHz, CDCl3) δ 173.5, 173.4, 150.3, 150.2,
144.2, 144.2, 142.5, 142.0, 141.6, 141.4, 131.9, 131.4,
128.9, 128.8, 127.0, 126.6, 126.1, 126.0, 125.4, 125.4,
125.1, 120.8, 120.0, 119.7, 119.5, 115.7, 115.6, 76.0, 75.2,
67.3, 67.2, 48.2, 47.8, 47.5, 47.4, 31.3, 31.1, 30.2, 29.9,
25.9, 25.3, 22.1, 22.1. HRMS (ESI), m/z calcd. for
C22H23N2O2 ([M+H]+) 347.1754, found: 347.1748.
1.36-1.26 (m, 1H). 13C NMR (100 MHz, CDCl3) δ 172.6,
172.5, 149.3, 149.2, 144.1, 144.0, 143.9, 143.3, 131.9,
131.4, 131.2, 131.1, 129.9, 129.4, 127.7, 127.4, 126.3,
126.2, 126.1, 125.9, 125.6, 125.6, 122.6, 121.7, 120.0,
119.8, 115.8, 115.7, 75.8, 75.0, 67.4, 67.4, 48.1, 47.9, 47.9,
47.5, 31.5, 31.4, 30.1, 29.6, 25.7, 25.4. HRMS (ESI), m/z
calcd. for C21H20BrN2O2 ([M+H]+) 411.0703, found:
411.0699.
3-methoxy-5-methyl-5-((tetrahydrofuran-2-
3-iodo-5-methyl-5-((tetrahydrofuran-2-
yl)methyl)benzo[4,5]imidazo[2,1-a]isoquinolin-6(5H)-
one (3i). Flash column chromatography (petroleum
ether/ethyl acetate = 8:1) gave 85 mg of product as a white
yl)methyl)benzo[4,5]imidazo[2,1-a]isoquinolin-6(5H)-
one (3m). Flash column chromatography (petroleum
ether/ethyl acetate = 10:1) gave 93 mg of product as a
o
1
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1
solid in 78% yield; mp: 90-91 C; H NMR (400 MHz,
CDCl3) δ 8.48-8.27 (m, 2H), 7.83-7.72 (m, 1H), 7.46-7.30
(m, 2H), 7.07-6.88 (m, 2H), 3.91 (s, 3H), 3.57-3.33 (m,
2.3H), 3.19 (dd, J = 15.2, 7.2 Hz, 0.7H), 2.70 (dd, J = 14.0,
11.2 Hz, 0.7H), 2.56 (dd, J = 14.0, 7.2 Hz, 0.3H), 2.42 (dd,
J = 14.0, 5.2 Hz, 0.3H), 2.11 (dd, J = 14.0, 3.6 Hz, 0.7H),
1.89-1.71 (m, 2H), 1.71-1.54 (m, 3H), 1.51-1.38 (m, 1H),
1.34-1.22 (m, 1H). 13C NMR (100 MHz, CDCl3) δ 173.3,
173.3, 162.6, 162.4, 150.2, 150.2, 144.3, 144.2, 143.8,
143.5, 131.8, 131.4, 128.1, 127.9, 125.9, 125.3, 125.2,
124.8, 119.5, 119.3, 116.4, 115.6, 115.6, 115.5, 113.7,
113.1, 112.2, 112.2, 75.9, 75.2, 67.3, 67.2, 55.7, 48.3, 48.0,
47.8, 47.6, 31.3, 31.2, 30.3, 29.8, 25.9, 25.3. HRMS (ESI),
m/z calcd. for C22H23N2O3 ([M+H]+) 363.1703, found:
363.1709.
white solid in 68% yield; mp: 124-125 C; H NMR (400
MHz, CDCl3) δ 8.43-8.29 (m, 1H), 8.27-8.11 (m, 1H),
7.92-7.70 (m, 3H), 7.52-7.35 (m, 2H), 3.57-3.45 (m, 1H),
3.45-3.29 (m, 1.5H), 3.17 (dd, J = 14.4, 6.8 Hz, 0.5H),
2.70 (dd, J = 13.6, 11.6 Hz, 0.5H), 2.56 (dd, J = 14.0, 6.8
Hz, 0.5H), 2.36 (dd, J = 14.0, 6.0 Hz, 0.5H), 2.12 (dd, J =
14.0, 3.2 Hz, 0.5H), 1.90-1.71 (m, 3H), 1.69-1.39 (m, 3H),
1.37-1.21 (m, 1H). 13C NMR (100 MHz, CDCl3) δ 172.5,
172.4, 149.4, 149.3, 144.1, 144.0, 143.7, 143.2, 136.9,
135.8, 135.4, 131.9, 131.4, 127.5, 127.2, 126.2, 126.0,
125.6, 125.6, 123.0, 122.2, 120.0, 119.8, 115.8, 115.7, 98.5,
98.2, 75.8, 75.0, 67.4, 67.4, 48.1, 47.8, 47.6, 47.3, 31.4,
31.3, 30.1, 29.6, 25.7, 25.4. HRMS (ESI), m/z calcd. for
C21H20IN2O2 ([M+H]+) 459.0564, found: 459.0569.
5-methyl-6-oxo-5-((tetrahydrofuran-2-yl)methyl)-5,6-
dihydrobenzo[4,5]imidazo[2,1-a]isoquinoline-3-
5-methyl-3-phenyl-5-((tetrahydrofuran-2-
yl)methyl)benzo[4,5]imidazo[2,1-a]isoquinolin-6(5H)-
one (3j). Flash column chromatography (petroleum
ether/ethyl acetate = 10:1) gave 95 mg of product as a light
carbonitrile (3n). Flash column chromatography
(petroleum ether/ethyl acetate = 20:3) gave 67 mg of
product as a white solid in 63% yield; mp: 101-102 oC; 1H
NMR (400 MHz, CDCl3) δ 8.65-8.50 (m, 1H), 8.42-8.32
(m, 1H), 7.88-7.69 (m, 3H), 7.54-7.38 (m, 2H), 3.58-3.49
(m, 0.5H), 3.48-3.34 (m, 1H), 3.34-3.23 (m, 1H), 3.16 (dd,
J = 14.8, 6.8 Hz, 0.5H), 2.76 (dd, J = 14.0, 11.6 Hz, 0.5H),
2.60 (dd, J = 14.4, 5.2 Hz, 0.5H), 2.31 (dd, J = 14.0, 7.6
Hz, 0.5H), 2.17 (dd, J = 14.0, 3.2 Hz, 0.5H), 1.91-1.73 (m,
3H), 1.72-1.44 (m, 3.5H), 1.38-1.26 (m, 0.5H). 13C NMR
(100 MHz, CDCl3) δ 172.0, 148.3, 148.0, 144.1, 144.0,
143.3, 142.3, 131.9, 131.5, 130.9, 130.8, 130.6, 130.5,
127.5, 126.9, 126.6, 126.6, 126.5, 126.4, 126.3, 125.9,
120.4, 120.3, 118.4, 118.3, 115.9, 115.8, 114.7, 114.6, 75.8,
74.9, 67.6, 67.5, 48.1, 48.0, 47.5, 31.9, 31.3, 30.0, 29.5,
25.4, 25.4. HRMS (ESI), m/z calcd. for C22H20N3O2
([M+H]+) 358.1550, found: 358.1547.
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green solid in 78% yield; mp: 165-166 C; H NMR (400
MHz, CDCl3) δ 8.67-8.48 (m, 1H), 8.46-8.28 (m, 1H),
7.91-7.79 (m, 1H), 7.77-7.59 (m, 4H), 7.56-7.35 (m, 5H),
3.61-3.33 (m, 2.5H), 3.21 (dd, J = 15.2, 7.2 Hz, 0.5H),
2.77 (dd, J = 13.6, 11.2 Hz, 0.5H), 2.64 (dd, J = 13.6, 7.2
Hz, 0.5H), 2.53 (dd, J = 13.6, 5.6 Hz, 0.5H), 2.24 (dd, J =
14.0, 3.2 Hz, 0.5H), 1.92-1.78 (m, 2H), 1.78-1.47 (m,
4.5H), 1.38-1.27 (m, 0.5H). 13C NMR (100 MHz, CDCl3)
δ 173.3, 173.3, 149.9, 149.9, 144.6, 144.4, 144.3, 144.2,
142.2, 141.9, 140.2, 140.1, 131.9, 131.5, 129.1, 128.4,
128.3, 127.3, 126.7, 126.5, 126.0, 125.6, 125.5, 125.3,
124.8, 122.3, 121.5, 119.9, 119.7, 115.8, 115.7, 76.0, 75.2,
67.3, 67.3, 48.2, 47.9, 47.8, 47.6, 31.4, 30.3, 29.9, 25.8,
25.4. HRMS (ESI), m/z calcd. for C27H25N2O2 ([M+H]+)
409.1911, found: 409.1917.
5-methyl-5-((tetrahydrofuran-2-yl)methyl)-3-
3-chloro-5-methyl-5-((tetrahydrofuran-2-
(trifluoromethyl)benzo[4,5]imidazo[2,1-a]isoquinolin-
6(5H)-one (3o). Flash column chromatography (petroleum
ether/ethyl acetate = 15:1) gave 80 mg of product as a
yl)methyl)benzo[4,5]imidazo[2,1-a]isoquinolin-6(5H)-
one (3k). Flash column chromatography (petroleum
ether/ethyl acetate = 15:1) gave 87 mg of product as a
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1
white solid in 67% yield; mp: 105-106 C; H NMR (400
MHz, CDCl3) δ 8.69-8.53 (m, 1H), 8.47-8.31 (m, 1H),
7.91-7.65 (m, 3H), 7.53-7.37 (m, 2H), 3.62-3.50 (m, 0.5H),
3.49-3.36 (m, 1H), 3.34-3.24 (m, 1H), 3.17 (dd, J = 14.8,
7.2 Hz, 0.5H), 2.76 (dd, J = 14.0, 11.6 Hz, 0.5H), 2.60 (dd,
J = 14.0, 5.6 Hz, 0.5H), 2.38 (dd, J = 14.0, 7.2 Hz, 0.5H),
2.20 (dd, J = 14.0, 3.2 Hz, 0.5H), 1.9-1.74 (m, 3H), 1.74-
1.54 (m, 3H), 1.38-1.27 (m, 1H). 13C NMR (100 MHz,
CDCl3) δ 172.5, 148.7, 148.6, 144.1, 144.0, 143.0, 142.1,
133.0 (q, J = 28.7 Hz), 131.9, 131.5, 126.9, 126.8, 126.5,
126.3, 126.0, 125.9, 125.9, 125.8, 124.6, 124.5 (q, J = 3.6
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white solid in 79% yield; mp: 139-140 C; H NMR (400
MHz, CDCl3) δ 8.50-8.27 (m, 2H), 7.87-7.70 (m, 1H),
7.54-7.32 (m, 4H), 3.55-3.28 (m, 2.5H), 3.17 (dd, J = 14.8,
7.2 Hz, 0.5H), 2.71 (dd, J = 14.0, 11.6 Hz, 0.5H), 2.57 (dd,
J = 14.0, 6.4 Hz, 0.5H), 2.36 (dd, J = 14.0, 6.4 Hz, 0.5H),
2.12 (dd, J = 14.0, 3.2 Hz, 0.5H), 1.91-1.71 (m, 2.5H),
1.69-1.39 (m, 4H), 1.36-1.22 (m, 0.5H). 13C NMR (100
MHz, CDCl3) δ 172.6, 172.5, 149.2, 149.1, 144.1, 144.0,
143.7, 143.1, 137.9, 137.6, 131.8, 131.4, 128.3, 128.2,
127.6, 127.3, 126.9, 126.4, 126.1, 125.8 , 125.6, 125.5,
5
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