4126
A.-L. Ge´rard et al. / Tetrahedron Letters 48 (2007) 4123–4126
´
9. Gerard, A.-L.; Bouillon, A.; Mahatsekake, C.; Collot, V.;
87%); mp 132 ꢁC; IR (KBr): 3097, 1766 (CO), 1618,
1
Rault, S. Tetrahedron Lett. 2006, 47, 4665–4669.
1578, 1455, 1419, 1316, 1277, 1167, 1097 cmÀ1; H NMR
10. Young, M. B.; Barrow, J. C.; Glass, K. L.; Lundell, G. F.;
Newton, C. L.; Pellicore, J. M.; Rittle, K. E.; Selnick, H.
G.; Stauffer, K. J.; Vacca, J. P.; Williams, P. D.; Bohn, D.;
Clayton, F. C.; Cook, J. J.; Krueger, J. A.; Kuo, L. C.;
Lewis, S. D.; Lucas, B. J.; McMasters, D. R.; Miller-Stein,
C.; Pietrak, B. L.; Wallace, A. A.; White, R. B.; Wong, B.;
Yan, Y.; Nantermet, P. G. J. Med. Chem. 2004, 47, 2995–
3008.
(400 MHz, CDCl3): d 7.75 (d, 1H, J = 1.9 Hz, H7), 7.72 (d,
1H, J = 1.2 Hz, H2), 7.53 (dd, 1H, J = 8.0, 1.9 Hz, H5),
7.37 (d, 1H, J = 8.0 Hz, H4), 6.35 (d, 1H, J = 1.2 Hz, H3);
13C NMR (100 MHz, CDCl3): d 158.67, 149.88, 145.50,
135.94, 134.61, 133.11, 130.14, 126.92, 122.32, 103.24;
HRMS Calcd for C10H5ClN2O, 204.0090; found,
204.0082. 6-Nitro-8H-pyrazolo[5,1-a]isoindol-8-one (11):
yellow solid (0.32 g, 50%); mp 199 ꢁC; IR (KBr): 3142,
3101, 1769 (CO), 1621, 1528, 1342, 1276, 1201, 1145,
11. (a) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457–
2483; (b) Suzuki, A. J. Organomet. Chem. 1999, 576, 147–
168; (c) Kotha, S.; Kashinath, D. Tetrahedron 2002, 58,
1
1063 cmÀ1; H NMR (400 MHz, CDCl3): d 8.62 (d, 1H,
J = 2.2 Hz, H7), 8.50 (dd, 1H, J = 8.3, 2.2 Hz, H5), 7.83
(d, 1H, J = 1.3 Hz, H2), 7.65 (d, 1H, J = 8.3 Hz, H4), 6.57
(d, 1H, J = 1.3 Hz, H3); 13C NMR (100 MHz, CDCl3): d
157.45, 150.30, 148.71, 144.34, 136.90, 132.74, 130.36,
121.79, 121.77, 105.32; LCMS (ESI) 216 (M+H). Anal.
Calcd for C10H5N3O3: C, 55.82; H, 2.34; N, 19.53. Found:
C, 55.55; H, 2.19; N, 19.33. 8H-Pyrazolo[5,1-a]isoindol-8-
one (14): yellow solid (0.17 g, 55%); mp 158 ꢁC; IR (KBr):
3136, 3107, 1746 (CO), 1618, 1579, 1469, 1426, 1328, 1309,
´
9633–9695; (d) Gerard, A.-L.; Lisowski, V.; Rault, S.
Tetrahedron 2005, 61, 6082–6086.
12. Typical procedure for the synthesis of pyrazoloisoindolones:
5-fluoro-8H-pyrazolo[5,1-a]isoindol-8-one (19). A solution
of 18 (1 g, 3.44 mmol) in CH2Cl2 (50 mL) was treated with
thionyl dichloride (0.3 mL, 4.13 mmol) and was refluxed
under stirring for 1 h. After removing the solvent under
reduced pressure, the residue was dissolved in AcOEt
(50 mL) and the solution was washed with saturated
aqueous sodium hydrogen carbonate solution (50 mL) and
water (2 · 50 mL), dried over MgSO4, filtered and evap-
orated to give 5-fluoropyrazoloisoindolone 19 as a yellow
solid that was crystallized from n-hexane. (0.45 g, 70%);
mp 164 ꢁC; IR (KBr): 3119, 3042, 1755 (CO), 1622, 1585,
1273, 1207, 1168 cmÀ1 1H NMR (400 MHz, CDCl3): d
;
7.78 (d, 1H, J = 7.5 Hz, Hphenyl), 7.71 (d, 1H, J = 1.5 Hz,
H2), 7.56 (td, 1H, J = 7.5, 1.2 Hz, Hphenyl), 7.43 (d, 1H,
J = 8.0 Hz, Hphenyl), 7.39 (td, 1H, J = 7.5, 0.9 Hz, Hphenyl),
6.34 (d, 1H, J = 1.5 Hz, H3); 13C NMR (100 MHz,
CDCl3): d 159.97, 149.49, 146.25, 134.86, 132.01, 131.48,
129.63, 126.54, 121.33, 102.78; LCMS (ESI) 171 (M+H).
Anal. Calcd for C10H6N2O: C, 70.58; H, 3.55; N, 16.46.
Found: C, 70.35; H, 3.43; N, 16.69. 6-Methoxy-8H-
pyrazolo[5,1-a]isoindol-8-one (15): yellow solid (0.6 g,
90%); mp 154 ꢁC; IR (KBr): 3095, 2948, 1764 (CO),
1472, 1407, 1335, 1306, 1289, 1220, 1188, 1161, 1075 cmÀ1
;
1H NMR (400 MHz, CDCl3): d 7.79 (dd, 1H, J = 8.3,
4.9 Hz, Hphenyl), 7.73 (d, 1H, J = 1.3 Hz, H2), 7.15 (dd,
1H, J = 7.8, 2.2 Hz, Hphenyl), 7.06 (td, 1H, J = 8.5, 2.2 Hz,
Hphenyl), 6.38 (d, 1H, J = 1.3 Hz, H3); 13C NMR
(100 MHz, CDCl3): d 167.02 (d, 1J = 255 Hz), 158.84,
149.39, 144.76, 134.59 (d, 3J = 10.7 Hz), 128.78 (d,
3J = 10.7 Hz), 127.18 (d, 4J = 3.3 Hz), 116.19 (d, 2J =
1615, 1579, 1483, 1425, 1326, 1289, 1249, 1203,1143 cmÀ1
;
1H NMR (400 MHz, CDCl3): d 7.65 (d, 1 H, J = 1.3 Hz,
H2); 7.32 (m, 2H, Hphenyl); 7.02 (dd, 1H, J = 8.3, 2.4 Hz,
2
23.1 Hz), 109.81 (d, J = 25.6 Hz), 103.55; HRMS Calcd
Hphenyl); 6.21 (d, 1H, J = 1.3 Hz, H3); 3.86 (s, 3H, OCH3);
for C10H5FN2O, 188.0386; found, 188.0377. Anal. Calcd
for C10H5FN2O: C, 63.83; H, 2.68; N, 14.89. Found: C,
63.68; H, 2.56; N, 14.67.
13C NMR (100 MHz, CDCl3): d 161.15, 159.98, 149.68,
146.64, 133.42, 124.34, 122.50, 119.91, 112.31, 101.70,
55.88; LCMS (ESI) 201 (M+H). Anal. Calcd for
C11H8N2O2: C, 66.00; H, 4.03; N, 13.99. Found: C,
65.87; H, 3.86; N, 13.72.
13. Spectroscopic data for novel pyrazoloisoindolones: 6-chloro-
8H-pyrazolo[5,1-a]isoindol-8-one (10): yellow solid (0.14 g,