PAPER
Synthesis of Pyrazolo[5,1-a]isoquinolines
3689
(2-Phenyl-6,10b-dihydro-5H-pyrazolo[5,1-a]isoquinolin-3-yl)-
p-tolylmethanone (5a)
Yield: 81 mg (89%); colorless crystals; mp 149–150 °C.
IR (film): 3007, 2930, 2856, 1659, 1647, 1605, 1493, 1323 cm–1.
MS (EI): m/z (%) = 115.1 (12), 260.1 (100) [M+].
HRMS (EI): m/z [M+] calcd for C18H16N2: 260.1314; found:
260.1321.
2-p-Tolyl-5,6-dihydropyrazolo[5,1-a]isoquinoline (6d)
Yield: 18 mg (80%); light-yellow solid; mp 111–112 °C.
IR (film): 2945, 2920, 1470, 1458, 1439, 1331, 824 cm–1.
1H NMR (300 MHz, CDCl3): d = 2.37 (s, 3 H, CH3), 3.22 (t, J = 5.2
Hz, 2 H, CH2-Ar), 4.38 (t, J = 5.2 Hz, 2 H, CH2-N), 6.81 (s, 1 H, Ar-
CH-N), 7.24–7.38 (m, 5 H, ArH), 7.58 (d, J = 5.6 Hz, 1 H, ArH),
7.73 (d, J = 6.1 Hz, 2 H, ArH).
13C NMR (100 MHz, CDCl3): d = 21.30, 29.23, 46.26, 97.39,
123.99, 125.41, 127.00, 127.40, 128.10, 128.23, 129.35, 130.69,
131.69, 137.41, 140.00, 151.41.
1H NMR (400 MHz, CDCl3): d = 2.36 (s, 3 H, CH3), 2.71 (dt,
J = 2.4, 16.0 Hz, 1 H, CH-N), 3.07 (dt, J = 4.1, 14.3 Hz, 1 H, CH-
Ar), 3.22 (dt, J = 2.5, 11.9 Hz, 1 H, CH-Ar), 3.44 (dq, J = 2.2, 10.2
Hz, 1 H, CH-N), 5.40 (s, 1 H, CH-Ar), 5.97 (d, J = 1.8 Hz, 1 H,
CH=C), 7.07 (d, J = 7.3 Hz, 1 H, ArH), 7.12–7.32 (m, 8 H, ArH),
7.47 (dd, J = 1.4, 6.8 Hz, 2 H, ArH), 7.75 (d, J = 8.1 Hz, 2 H, ArH).
13C NMR (100 MHz, CDCl3): d = 21.53, 28.42, 47.81, 66.96,
117.99, 125.52, 126.26, 126.48, 126.79, 126.95, 128.17, 128.28,
128.37, 128.45, 128.65, 128.93, 129.20, 130.21, 132.25, 132.36,
133.21, 134.07, 141.50, 143.69, 172.29.
MS (EI): m/z (%) = 247 (100), 366.2 (3) [M+].
HRMS (EI): m/z [M+] calcd for C25H22N2O: 366.1732; found:
MS (EI): m/z (%) = 162.0 (14), 260.1 (100) [M+].
HRMS (EI): m/z [M+] calcd for C18H16N2: 260.1314; found:
366.1741.
260.1305.
2-Phenyl-5,6-dihydropyrazolo[5,1-a]isoquinoline (6a)
Yield: 18 mg (84%); colorless solid; mp 83–84 °C (Lit.9d 88–
89 °C).
2-(6-Methoxynaphthalen-2-yl)-5,6-dihydropyrazolo[5,1-a]iso-
quinoline (6e)
Yield: 19 mg (66%); orange crystalline solid; mp 165–166 °C.
IR (film): 3053, 2947, 2924, 2895, 2870, 1487, 1468, 1454, 1337,
1078 cm–1.
1H NMR (300 MHz, CDCl3): d = 3.25 (t, J = 6.9 Hz, 2 H, CH2-Ar),
4.43 (t, J = 6.9 Hz, 2 H, CH2-N), 6.89 (s, 1 H, Ar-CH-N), 7.26–7.48
(m, 6 H, ArH), 7.63 (d, J = 7.2 Hz, 1 H, ArH), 7.88–7.91 (m, 2 H,
ArH).
13C NMR (100 MHz, CDCl3): d = 29.60, 46.70, 98.01, 124.42,
125.91, 127.33, 127.84, 128.09, 128.58, 128.66, 129.08, 132.08,
133.90, 140.49, 151.71.
IR (film): 3001, 2953, 2945, 2930, 2899, 2870, 2837, 1632, 1607,
1497, 1391, 1215, 1030 cm–1.
1H NMR (300 MHz, CDCl3): d = 3.28 (t, J = 6.9 Hz, 2 H, CH2-Ar),
3.96 (s, 3 H, CH3), 4.47 (t, J = 6.8 Hz, 2 H, CH2-N), 6.98 (s, 1 H,
Ar-CH-N), 7.16–7.20 (m, 2 H, ArH), 7.30–7.40 (m, 3 H, ArH), 7.65
(d, J = 7.3 Hz, 1 H, ArH), 7.80–7.84 (m, 2 H, ArH), 8.00 (dd,
J = 1.8, 8.6 Hz, 1 H, ArH), 8.27 (d, J = 1.1 Hz, 1 H, ArH).
13C NMR (100 MHz, CDCl3): d = 29.22, 46.32, 55.34, 97.62,
105.80, 119.04, 123.94, 124.05, 124.52, 126.92, 127.14, 127.46,
128.23, 128.27, 128.73, 129.12, 129.73, 131.71, 134.23, 140.21,
151.42, 157.72.
MS (EI): m/z (%) = 119.0 (19), 246.1 (100) [M+].
HRMS (EI): m/z [M+] calcd for C17H14N2: 246.1157; found:
246.1149.
MS (EI): m/z (%) = 283.1 (20), 326.1 (100) [M+].
HRMS (EI): m/z [M+] calcd for C22H18N2O: 326.1419; found:
326.1398.
2-o-Tolyl-5,6-dihydropyrazolo[5,1-a]isoquinoline (6b)
Yield: 18 mg (80%); light-yellow oil.
IR (film): 3049, 2953, 2924, 2897, 2870, 1487, 1468, 1456, 1329,
953 cm–1.
2-(4-Bromophenyl)-5,6-dihydropyrazolo[5,1-a]isoquinoline (6f)
Yield: 22 mg (77%); yellow crystalline solid; mp 104–105 °C.
1H NMR (300 MHz, CDCl3): d = 2.52 (s, 3 H, CH3), 3.25 (t, J = 5.2
Hz, 2 H, CH2-Ar), 4.40 (t, J = 5.2 Hz, 2 H, CH2-N), 6.68 (s, 1 H, Ar-
CH-N), 7.22–7.33 (m, 6 H, ArH), 7.57–7.63 (m, 2 H, ArH).
13C NMR (100 MHz, CDCl3): d = 21.26, 29.24, 46.22, 100.75,
123.97, 125.82, 127.06, 127.40, 127.65, 128.06, 128.26, 129.24,
130.75, 131.69, 133.42, 135.98, 139.15, 151.60.
IR (film): 3049, 2945, 2924, 2895, 2874, 1468, 1423, 1327, 1009,
953 cm–1.
1H NMR (300 MHz, CDCl3): d = 3.26 (t, J = 7.0 Hz, 2 H, CH2-Ar),
4.42 (t, J = 7.1 Hz, 2 H, CH2-N), 6.85 (s, 1 H, Ar-CH-N), 7.29–7.40
(m, 3 H, ArH), 7.56 (dt, J = 2.2, 8.6 Hz, 2 H, ArH), 7.61 (dt, J = 1.2,
7.1 Hz, 1 H, ArH), 7.75 (dt, J = 2.2, 8.6 Hz, 2 H, ArH).
MS (EI): m/z (%) = 111.0 (38), 260.1 (100) [M+].
HRMS (EI): m/z [M+] calcd for C18H16N2: 260.1314; found:
13C NMR (100 MHz, CDCl3): d = 29.16, 46.34, 97.56, 121.51,
124.02, 126.75, 127.05, 127.48, 128.28, 128.32, 131.66, 131.75,
132.49, 140.28, 150.22.
260.1302.
MS (EI): m/z (%) = 115 (31), 324 (100) [M+].
2-m-Tolyl-5,6-dihydropyrazolo[5,1-a]isoquinoline (6c)
Yield: 17 mg (78%); light-yellow oil.
HRMS (EI): m/z [M+] calcd for C17H13BrN2: 324.0262; found:
324.0269.
IR (film): 3015, 2949, 2920, 2870, 1487, 1470, 1329, 1248, 1217,
1013 cm–1.
1H NMR (300 MHz, CDCl3): d = 2.44 (s, 3 H, CH3), 3.26 (t, J = 6.9
Hz, 2 H, CH2-Ar), 4.43 (t, J = 6.9 Hz, 2 H, CH2-N), 6.88 (s, 1 H, Ar-
CH-N), 7.16 (d, J = 7.5 Hz, 1 H, ArH), 7.29–7.38 (m, 4 H, ArH),
7.61–7.74 (m, 3 H, ArH).
2-(4-Fluorophenyl)-5,6-dihydropyrazolo[5,1-a]isoquinoline
(6g)
Yield: 17 mg (75%); yellow crystalline solid; mp 78–79 °C.
IR (film): 3053, 2923, 2870, 2851, 1526, 1468, 1439, 1217, 1153,
839 cm–1.
13C NMR (100 MHz, CDCl3): d = 21.92, 29.61, 46.68, 98.04,
123.08, 124.40, 126.52, 127.35, 127.82, 128.55, 128.65, 128.88,
128.97, 132.07, 133.74, 138.68, 140.43, 151.84.
1H NMR (300 MHz, CDCl3): d = 3.26 (t, J = 6.8 Hz, 2 H, CH2-Ar),
4.42 (t, J = 6.8 Hz, 2 H, CH2-N), 6.82 (s, 1 H, Ar-CH-N), 7.09–7.16
(m, 2 H, ArH), 7.29–7.39 (m, 3 H, ArH), 7.61 (dt, J = 1.1, 7.1 Hz,
1 H, ArH), 7.81–7.87 (m, 2 H, ArH).
Synthesis 2007, No. 23, 3683–3691 © Thieme Stuttgart · New York