6498
J. Sheng et al. / Tetrahedron 69 (2013) 6495e6499
NMR (100 MHz, CDCl3)
127.0, 127.0, 127.1, 129.0, 129.3, 129.6, 131.2, 134.4, 138.7, 139.1, 140.2.
d
14.1, 19.5, 21.4, 112.0, 117.0, 123.2, 125.4,
116.9, 123.0, 125.5, 127.0, 127.2, 128.3, 128.6, 129.0, 129.4, 134.2,
134.3, 137.0, 137.8, 140.0.
4.1.11. 1-Ethyl-5-(4-methoxyphenyl)pyrazolo[5,1-a]isoquinoline
4.1.19. 5-Cyclopropyl-1-ethyl-9-methylpyrazolo[5,1-a]isoquinoline
(3k). White solid; 1H NMR (400 MHz, CDCl3)
d
1.45 (t, J¼7.5 Hz, 3H), 3.10
(3s).3k Yellow solid; 1H NMR (400 MHz, CDCl3)
d 0.86e0.90 (m, 2H),
(q, J¼7.5 Hz, 2H), 3.87 (s, 3H), 6.94 (s,1H), 7.04 (d, J¼8.7 Hz, 2H), 7.48e7.57
1.14e1.19 (m, 2H), 1.45 (t, J¼7.5 Hz, 3H), 2.53 (s, 3H), 2.60e2.66 (m,
1H), 3.09 (q, J¼7.5 Hz, 2H), 6.58 (s, 1H), 7.29 (d, J¼8.0 Hz, 1H), 7.52
(d, J¼8.0 Hz, 1H), 7.90 (s, 1H), 7.99 (s, 1H); 13C NMR (100 MHz,
(m, 2H), 7.71 (d, J¼7.6 Hz, 1H), 7.79e7.81 (m, 2H), 7.84 (s, 1H), 8.24 (d,
J¼8.0 Hz, 1H); 13C NMR (100 MHz, CDCl3)
d 14.1, 19.5, 55.4, 111.8, 113.8,
117.1,123.2,125.3,126.5,126.9,127.0,129.6,130.8,134.5,138.4,140.2,160.2;
CDCl3) d 6.7, 11.4, 14.1, 19.5, 21.9, 106.7, 116.9, 122.9, 124.8, 126.4,
HRMS (ESI) calcd for C20H18N2O: 303.1492 (MþH)þ, found: 303.1510.
127.2, 128.4, 133.9, 136.2, 139.8.
4.1.12. 5-Cyclopropyl-1-ethylpyrazolo[5,1-a]isoquinoline (3l).3k Yellow
4.1.20. 1-Ethyl-8-methoxy-5-phenylpyrazolo[5,1-a]isoquinoline
solid; 1H NMR (400 MHz, CDCl3)
d
0.87e0.91 (m, 2H), 1.15e1.20 (m,
(3t). White solid; 1H NMR (400 MHz, CDCl3)
d
1.44 (t, J¼7.4 Hz, 3H),
2H), 1.44 (t, J¼7.5 Hz, 3H), 2.62e2.69 (m, 1H), 3.08 (q, J¼7.5 Hz, 2H),
3.07 (q, J¼7.4 Hz, 2H), 3.92 (s, 3H), 6.91 (s, 1H), 7.13 (d, J¼2.0 Hz, 1H),
6.60 (s, 1H), 7.43e7.51 (m, 2H), 7.61 (d, J¼7.6 Hz,1H), 7.91 (s,1H), 8.19
7.19 (dd, J1¼2.0 Hz, J2¼8.8 Hz, 1H), 7.46e7.54 (m, 3H), 7.83e7.86 (m,
(d, J¼7.8 Hz, 1H); 13C NMR (100 MHz, CDCl3)
d
6.8, 11.4, 14.1, 19.4,
3H), 8.16 (d, J¼8.8 Hz, 1H); 13C NMR (100 MHz, CDCl3)
d 14.1, 19.4,
106.7, 117.1, 123.1, 124.7, 126.4, 126.5, 126.8, 129.4, 134.0, 140.0, 140.8.
55.4, 108.5, 112.1, 115.7, 116.6, 119.6, 124.8, 128.3, 129.2, 129.4, 131.2,
134.2, 134.7, 139.0, 140.4, 158.6; HRMS (ESI) calcd for C20H18N2O:
309.1368 (MþNa)þ, found: 309.1371.
4.1.13. 1-Ethyl-9-fluoro-5-phenylpyrazolo[5,1-a]isoquinoline
(3m). White solid; 1H NMR (400 MHz, CDCl3)
d
1.46 (t, J¼7.5 Hz, 3H),
3.09 (q, J¼7.5 Hz, 2H), 6.96 (s, 1H), 7.24e7.28 (m, 1H), 7.47e7.54 (m,
4.1.21. 5-Cyclopropyl-1-ethyl-8-methoxypyrazolo[5,1-a]isoquinoline
3H), 7.71 (dd, J1¼5.8 Hz, J2¼8.6 Hz, 1H), 7.82e7.90 (m, 4H); 13C NMR
(3u). White solid; 1H NMR (400 MHz, CDCl3)
d 0.88e0.92 (m, 2H),
2
(100 MHz, CDCl3)
d
14.0, 19.3, 108.8 (d, JCF¼23.7 Hz), 111.7, 115.6 (d,
1.16e1.21 (m, 2H), 1.43 (t, J¼7.5 Hz, 3H), 2.63e2.70 (m, 1H), 3.06 (q,
2JCF¼23.4 Hz), 117.6, 126.0, 126.5, 128.4, 129.2, 129.2, 129.4, 133.9,
138.0, 140.3, 161.6 (d, 1JCF¼244.7 Hz); HRMS (ESI) calcd for C19H15FN2:
291.1292 (MþH)þ, found: 291.1300.
J¼7.5 Hz, 2H), 3.91 (s, 3H), 6.56 (s, 1H), 7.06 (d, J¼2.4 Hz, 1H), 7.13
(dd, J1¼2.5 Hz, J2¼8.9 Hz, 1H), 7.88 (s, 1H), 8.13 (d, J¼8.9 Hz, 1H); 13
C
NMR (100 MHz, CDCl3) d 6.9, 11.4, 14.2, 19.3, 55.3, 106.3, 107.9, 115.7,
115.9, 118.9, 124.7, 131.2, 134.3, 140.2, 141.3, 158.4; HRMS (ESI) calcd
4.1.14. 5-Cyclopropyl-1-ethyl-9-fluoropyrazolo[5,1-a]isoquinoline
for C17H18N2O: 267.1492 (MþH)þ, found: 267.1509.
(3n). Yellow solid; 1H NMR (400 MHz, CDCl3)
d 0.85e0.89 (m, 2H),
1.15e1.20 (m, 2H), 1.44 (t, J¼7.5 Hz, 3H), 2.59e2.66 (m, 1H), 3.03 (q,
4.1.22. 1-Ethyl-8,9-dimethoxy-5-phenylpyrazolo[5,1-a]isoquinoline
1
J¼7.5 Hz, 2H), 6.56 (s, 1H), 7.16e7.21 (m, 1H), 7.57 (dd, J1¼5.7 Hz,
(3v). White solid; H NMR (400 MHz, CDCl3)
d
1.47 (t, J¼7.5 Hz, 3H),
J2¼8.7 Hz,1H), 7.13 (dd, J1¼2.4 Hz, J2¼10.3 Hz, 1H), 7.91 (s, 1H); 13C NMR
3.10 (q, J¼7.5 Hz, 2H), 4.00 (s, 3H), 4.05 (s, 3H), 6.89 (s, 1H), 7.11 (s, 1H),
2
(100 MHz, CDCl3)
d
6.7, 11.3, 14.0, 19.2, 106.1, 108.5 (d, JCF¼23.6 Hz),
7.44e7.52 (m, 3H), 7.68 (s, 1H), 7.82e7.85 (m, 3H); 13C NMR (100 MHz,
2
3
115.3 (d, JCF¼23.3 Hz), 117.5, 125.6 (d, JCF¼9.3 Hz), 125.9, 128.4 (d,
3JCF¼9.8 Hz),133.3 (d, 4JCF¼3.7 Hz),140.0,140.1,161.1 (d,1JCF¼243.9 Hz);
HRMS (ESI) calcd for C16H15FN2: 255.1292 (MþH)þ, found: 255.1308.
CDCl3) d 14.4, 19.5, 55.9, 56.0, 104.4, 107.7, 111.9, 115.0, 119.7, 124.2, 128.3,
129.0, 129.3, 134.3, 137.1, 140.2, 149.4; HRMS (ESI) calcd for C21H20N2O2:
333.1598 (MþH)þ, found: 333.1592.
4.1.15. 1-Ethyl-8-fluoro-5-phenylpyrazolo[5,1-a]isoquinoline
4.1.23. 9-Ethyl-5-phenylpyrazolo[1,5-a]thieno[2,3-c]pyridine
(3o).3k White solid; 1H NMR (400 MHz, CDCl3)
d
1.44 (t, J¼7.5 Hz,
(3w). White solid; 1H NMR (400 MHz, CDCl3)
d
1.42 (t, J¼7.5 Hz, 3H),
3.09 (q, J¼7.5 Hz, 2H), 7.11 (s,1H), 7.37 (d, J¼5.6 Hz,1H), 7.46e7.54 (m,
4H), 7.84e7.86 (m, 3H); 13C NMR (100 MHz, CDCl3)
15.1, 17.9, 108.1,
3H), 3.06 (q, J¼7.5 Hz, 2H), 6.89 (s, 1H), 7.26e7.31 (m, 1H), 7.36 (dd,
J1¼2.5 Hz, J2¼9.3 Hz,1H), 7.46e7.54 (m, 3H), 7.82e7.85 (m, 3H), 7.36
d
(dd, J1¼5.3 Hz, J2¼8.9 Hz, 1H); 13C NMR (100 MHz, CDCl3)
d
13.9,
113.6, 124.1, 126.3, 127.3, 128.4, 129.1, 129.3, 134.0, 134.2, 134.4, 137.8,
140.2; HRMS (ESI) calcd for C17H14N2S: 279.0950 (MþH)þ, found:
279.0969.
2
2
19.4, 111.5, 112.0 (d, JCF¼21.5 Hz), 115.5 (d, JCF¼23.3 Hz), 116.6,
3
122.0, 125.3 (d, JCF¼8.7 Hz), 128.4, 129.3, 129.4, 131.3 (d,
3JCF¼9.0 Hz), 133.7, 134.2, 139.7, 140.6, 161.4 (d, 1JCF¼245.9 Hz).
Acknowledgements
4.1.16. 5-Cyclopropyl-1-ethyl-8-fluoropyrazolo[5,1-a]isoquinoline
1
(3p).3k Yellow solid; H NMR (400 MHz, CDCl3)
d 0.88e0.92 (m, 2H),
Financial support from National Natural Science Foundation of
China (No. 21032007) is gratefully acknowledged.
1.17e1.22 (m, 2H), 1.44 (t, J¼7.5 Hz, 3H), 2.64e2.71 (m, 1H), 3.05 (q,
J¼7.5 Hz, 2H), 6.53 (s, 1H), 7.21e7.29 (m, 2H), 7.91 (s,1H), 8.14e8.18 (m,
1H); 13C NMR (100 MHz, CDCl3)
d 7.0, 11.4, 14.0, 19.4, 105.8, 111.4 (d,
Supplementary data
2JCF¼21.5 Hz), 114.8 (d, 2JCF¼23.2 Hz), 116.6, 121.3, 125.2 (d, 3JCF¼8.7 Hz),
131.3 (d, 3JCF¼8.8 Hz), 133.8, 140.3, 142.1, 161.3 (d, 1JCF¼245.6 Hz).
Supplementary data related to this article can be found at http://
4.1.17. 9-Chloro-1-ethyl-5-phenylpyrazolo[5,1-a]isoquinoline
(3q).3k White solid; 1H NMR (400 MHz, CDCl3)
d
1.47 (t, J¼7.2 Hz,
References and notes
3H), 3.06 (q, J¼7.2 Hz, 2H), 6.92 (s, 1H), 7.44e7.52 (m, 4H), 7.64 (d,
J¼8.3 Hz, 1H), 7.82e7.87 (m, 3H), 8.17 (s, 1H); 13C NMR (100 MHz,
CDCl3) d 13.8, 19.3, 111.6, 117.6, 122.6, 126.4, 126.9, 127.5, 127.8, 128.4,
128.5, 129.3, 132.8, 133.4, 133.7, 138.9, 140.4.
4.1.18. 1-Ethyl-9-methyl-5-phenylpyrazolo[5,1-a]isoquinoline
(3r).3k Yellow solid; 1H NMR (400 MHz, CDCl3)
d
1.49 (t, J¼7.4 Hz,
3H), 2.58 (s, 3H), 3.14 (q, J¼7.4 Hz, 2H), 6.95 (s,1H), 7.35 (d, J¼8.0 Hz,
1H), 7.47e7.55 (m, 3H), 7.63 (d, J¼8.0 Hz, 1H), 7.86e7.87 (m, 3H),
8.05 (s, 1H); 13C NMR (100 MHz, CDCl3)
d 14.0, 19.5, 22.0, 112.3,