Structures of CLK/inhibitor complexes
(30 mL) it was dried over Na2SO4 and the solvent was evaporated under vacuum. Purification
by recrystallization from ethanol 96%.
Light yellow solid, mp 248–250˚C, 47 mg (29%); IR (KBr): 3409 cm-1(NH), 1691 cm-1
(C = O); 1H NMR (DMSO-d6, 400 MHz): δ 4.46 (s, 2H, CH2), 7.24 (d, 1H, J = 8.2 Hz), 7.33–
7.42 (m, 1H), 7.48–7.55 (m, 2H), 7.55–7.21 (m, 2H), 7.73 (d, 1H, J = 8.0 Hz), 8.49 (br s, 1H, pyr-
rolidone-NH), 12.52 (br s, 1H, indole-NH); 13C NMR (DMSO-d6, 101 MHz): δ 45.53 (CH2),
115.33, 121.66, 126.71, 128.59, 129.20 (CH), 109.14, 115.79, 116.14, 126.62, 130.25, 133.08,
140.09, 169.84 (C); C16H11BrN2O (327.2); MS (EI) m/z 326.0[M]+..
Synthesis of compounds 17a-17c. 5-Bromo-3-phenyl-6,7-dihydropyrrolo[3,4-g]indol-8
(1H)-one (12a) (1 equiv), tetrakistriphenylphosphinpalladium(0) (0.4 equiv), Cs2CO3 (3
equiv) and the respective phenylboronic acid (1.5 equiv) were suspended in toluene/ethanol (2
mL + 1 mL) in a microwave reactor. The reaction was executed using the following parame-
ters: ramp time: 5 min, reaction time: 20 min at 150˚C, irradiation: 200 W. After filtering the
crude product over silica gel (3 cm) the solvent was evaporated under vacuum. Purification
was done by recrystallization from ethanol or by preparative HPLC.
3,5-Diphenyl-6,7-dihydropyrrolo[3,4-g]indol-8(1H)-one (17a). From 5-bromo-3-phenyl-
6,7-dihydropyrrolo[3,4-g]indol-8(1H)-one (12a) (131 mg, 0.4 mmol), Tetrakistriphenylpho-
sphin-palladium(0) (4 mg, 3.4 μmol) and Cs2CO3 (254 mg, 0.78 mmol) and phenylboronic
acid (98 mg, 0.8 mmol). White yellow solid, mp 262–263˚C, 18 mg (14%); IR (KBr): 3417 cm-1
(NH), 1688 cm-1 (C = O); 1H NMR (DMSO-d6, 600 MHz): δ 4.56 (s, 2H, CH2), 7.27 (tt, 1H,
J = 1.2 Hz, 7.3 Hz), 7.39 (tt, 1H, J = 1.2 Hz, 7.4 Hz), 7.43–7.52 (m, 4H), 7.63–7.66 (m, 2H), 7.67
(d, 1H, J = 2.5 Hz), 7.71–7.77 (m, 2H), 8.02 (s, 1H), 8.58 (s, 1H, pyrrolidone-NH), 11.85 (d,
1H, J = 2.0 Hz, indole-NH); 13C NMR (DMSO-d6, 151 MHz): δ 45.62 (CH2); 122.29, 124.63,
125.61, 126.85 (2C), 128.21 (2C), 128.65 (2C), 128.81 (2C)(CH); 116.53, 116.87, 126.07, 128.71,
130.39, 135.04, 137.16, 139.74, 170.18 (C); C22H16N2O (324.4); MS (EI) m/z 324.1 [M]+.,
HRMS (EI) m/z [M]+. calcd 324.12571, obsd 324.12541.
5-(2-Fluorophenyl)-3-phenyl-6,7-dihydropyrrolo[3,4-g]indol-8(1H)-one (17b). From 5-bromo-
3-phenyl-6,7-dihydropyrrolo[3,4-g]indol-8(1H)-one (12a) (196 mg, 0.60 mmol), tetrakis-tri-
phenylphosphinpalladium(0) (28 mg, 0.024 mmol), Cs2CO3 (586 mg, 1.80 mmol) and 2-fluoro-
phenylboronic acid (126 mg, 0.90 mmol). Yellow solid, mp 136-139˚C, 11mg (5.4%); IR (KBr):
3417 cm-1 (NH), 3262 cm-1 (NH), 2922 cm-1, 1685 cm-1 (C = O); 1H NMR (DMSO-d6, 600
MHz): δ 4.36 (s, 2H, CH2), 7.24–7.28 (m, 1H), 7.30–7.39 (m, 2H), 7.41–7.51 (m, 3H), 7.61 (td,
1H, J = 1.8 Hz, 7.72 Hz), 7.70 (d, 1H, J = 2.6 Hz), 7.70–7.74 (m, 2H), 7.99 (s, 1H), 8.55 (br s, 1H,
pyrrolidone-NH), 11.93 (d, 1H, J = 2,6 Hz, indole-NH); 13C NMR (DMSO-d6, 151 MHz): δ
(ppm) = 45.21 (d, 5JC,F = 4.47 Hz, C-C-C-C-C-F) (CH2); 115.80 (d, 2JC,F = 22.44, Hz, C-C-F),
123.66, 124.71 (d, 4JC,F = 3.28 Hz, C-C-C-C-F), 124.78, 125.70, 126.86 (2C), 128.83 (2C), 129.55
(d, 3JC,F = 8.13 Hz, C-C-C-F), 131.66 (d, 4JC,F = 3.29 Hz, C-C-C-C-F) (CH); 116.52, 116.69,
122.36, 125.76, 126.76 (d, 2JC,F = 15.46 Hz, C-C-F), 130.61, 134.91, 138.11, 159.05 (d, 1JC,F
=
244.03 Hz, C-F), 170.09 (C); C22H15FN2O (342.4); MS (EI) m/z 342.1 [M]+., HRMS (EI) m/z
[M]+. calcd 342.11629, obsd 342.11663.
5-(3-Fluorophenyl)-3-phenyl-6,7-dihydropyrrolo[3,4-g]indol-8(1H)-one (17c). From
5-bromo-3-phenyl-6,7-dihydropyrrolo[3,4-g]indol-8(1H)-one (12a) (98 mg, 0.3 mmol), tetra-
kistriphenylphosphinpalladium(0) (14 mg, 0.012 mmol), Cs2CO3 (293 mg, 0.90 mmol) and
3-fluorophenylboronic acid (63 mg, 0.3 mmol). Grey solid, mp 246–247˚C, 32 mg (31%); IR
(KBr): 3416 cm-1 (NH), 1690 cm-1 (C = O); 1H NMR (DMSO-d6, 600 MHz): δ 4.48 (s, 1H,
CH2), 7.19–7.24 (m, 1H), 7,27 (tt, 1H, J = 1.2 Hz, 7.4 Hz), 7.42–7.47 (m, 2H), 7.48–7.55 (m,
3H), 7.68 (d, 1H, J = 2.6), 7.73–7.78 (m, 2H), 8.05 (s, 1H), 8.61 (br s, 1H, pyrrolidone-NH),
11.89 (d, 1H, J = 2.7 Hz, indole-NH); 13C NMR (DMSO-d6, 151 MHz): δ 45.53 (CH2); 113.68
(d, 2JC,F = 20.75 Hz, C-C-F), 114.98 (d, 2JC,F = 21.53 Hz, C-C-F), 122,53, 124.48 (d, 4JC,F = 2.55
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