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B. Boganyi, J. Kaman / Tetrahedron 69 (2013) 9512e9519
dichloromethane (50 mL) benzoyl chloride (2.84 g, 20.18 mmol)
and potassium carbonate solution (10%, 50 mL) were added at
0e10 ꢀC. The resulting two phase system was stirred vigorously at
room temperature overnight. The resulting precipitate was filtered
off and washed with dichloromethane. The title compound was
obtained as an off-white solid (2.03 g, 89%), mp 256e258 ꢀC; 1H
NMR (DMSO-d6, 400 MHz)
J¼7.6 Hz), 7.77 (d, 1H, J¼8.0 Hz), 7.67e7.59 (m, 2H), 7.39e7.32 (m,
3H), 7.09e7.03 (m, 1H); 13C NMR (DMSO-d6, 400 MHz)
149.5,
145.2, 140.1, 139.9, 130.0, 128.2, 126.7, 126.0, 124.6, 123.5, 122.4,
120.6, 107.7; C15H11BrN2 (299.17); LCMS (ESIþ) m/z 299, 301
[MþH]þ. Anal. Calcd for C15H11BrN2 (299.17) C, 60.22; H, 3.71; N,
9.36. Found: C, 60.13; H, 3.70; N, 9.38.
d 8.59 (s, 1H), 8.36 (br s, 1H), 7.91 (d, 2H,
d
NMR (DMSO-d6, 400 MHz)
d 12.09 (br s,1H), 8.70 (s,1H), 7.64 (d,1H,
J¼7.6 Hz), 7.56e7.50 (m, 1H), 7.31 (d, 1H, J¼8.4 Hz), 7.22e7.16 (m,
1H); 13C NMR (DMSO-d6, 400 MHz)
d
158.7, 148.7, 138.7, 130.7,
4.7.4. 2-Bromo-(3-phenylamino)quinoline (25). Prepared from 21.
126.9, 122.0, 120.2, 115.1, 95.7; C9H6INO (271.06); LCMS (ESIþ) m/z
272 [MþH]þ. Anal. Calcd for C9H6INO (271.06) C, 39.88; H, 2.23; N,
5.17. Found: C, 39.74; H, 2.24; N, 5.18.
Eluent: hexane/ethyl acetate (95/5). Yellow oil (126 mg, 70%), 1H
NMR (CDCl3, 400 MHz)
7.60e7.55 (m, 1H), 7.52e7.38 (m, 4H), 7.28 (s, 1H), 7.18e7.12 (m, 1H),
6.32 (br s, 1H); 13C NMR (CDCl3, 400 MHz)
142.8, 140.3, 136.3,
d
7.92 (d, 1H, J¼8.0 Hz), 7.69 (s, 1H),
d
4.6.4. 2-Bromo-3-iodoquinoline (21). To a stirred suspension of
3-iodo-1H-quinolin-2-one (20) (1.90 g, 6.99 mmol) in toluene
(20 mL) phosphorus oxybromide (2.01 g, 6.99 mmol) was added in
small portions at 0e10 ꢀC. The reaction mixture was refluxed for
3 h. After completion of the reaction the solvent was evaporated off,
the residue was dissolved in dichloromethane (40 mL) then washed
with potassium carbonate solution (10%, 20 mL) and water (20 mL).
The organic layer was dried over Na2SO4, filtered, and evaporated to
dryness. The crude product was recrystallized from isopropyl al-
cohol. The title compound was obtained as a beige solid (1.74 g,
136.2, 129.8, 128.7, 128.2, 127.5, 126.9, 126.0, 123.9, 121.2, 115.6;
C15H11BrN2 (299.17); LCMS (ESIþ) m/z 299, 301 [MþH]þ. Anal.
Calcd for C15H11BrN2 (299.17) C, 60.22; H, 3.71; N, 9.36. Found: C,
60.08; H, 3.70; N, 9.39.
4.7.5. 4-Bromo-3-(4-nitrophenylamino)quinoline (27a). Prepared
from 9 and 26a by irradiation at 130 ꢀC for 180 min. Eluent: hexane/
ethyl acetate (3/2). Yellow solid (156 mg, 76%), mp 189e190 ꢀC; 1H
NMR (CDCl3, 400 MHz)
d
8.94 (s, 1H), 8.19 (d, 2H, J¼8.8 Hz), 8.14 (d,
1H, J¼8.4 Hz), 8.10 (d, 1H, J¼8.0 Hz), 7.75e7.65 (m, 2H), 7.07 (d, 2H,
74%), mp 126e128 ꢀC; 1H NMR (DMSO-d6, 400 MHz)
d
9.02 (s, 1H),
J¼9.2 Hz), 6.54 (br s, 1H); 13C NMR (CDCl3, 400 MHz)
d 148.3, 145.7,
7.99e7.92 (m, 2H), 7.87e7.81 (m, 1H), 7.72e7.66 (m, 1H); 13C NMR
145.0, 141.6, 132.7, 129.8, 129.0, 128.7, 128.1, 126.2, 124.6, 115.2,
110.0; C15H10BrN3O2 (344.17); LCMS (ESIþ) m/z 344, 346 [MþH]þ.
Anal. Calcd for C15H10BrN3O2 (344.17) C, 52.35; H, 2.93; N, 12.21.
Found: C, 52.48; H, 2.92; N, 12.24.
(DMSO-d6, 400 MHz)
d 148.3, 146.3, 146.2, 131.2, 127.9, 127.8, 127.6,
127.1, 96.1; C9H5BrIN (333.96); LCMS (ESIþ) m/z 334, 336 [MþH]þ.
Anal. Calcd for C9H5BrIN (333.96) C, 32.37; H, 1.51; N, 4.19. Found: C,
32.25; H, 1.51; N, 4.20.
4.7.6. 4-Bromo-3-(4-fluorophenylamino)quinoline (27b). Prepared
from 9 and 26b by irradiation at 130 ꢀC 180 min. Eluent: hexane/
ethyl acetate (9/1). Yellow solid (114 mg, 60%), mp 120e122 ꢀC; 1H
4.7. General procedure for the BuchwaldeHartwig reactions
A microwave vial (2e5 mL) was charged with palladium acetate
(6.7 mg, 0.03 mmol), Xantphos (4,5-bis(diphenylphosphino)-9,9-
dimethylxanthene) (34.7 mg, 0.06 mmol), the requisite dihaloqui-
noline, i.e., 9, 12, 17 or 21 (200.0 mg, 0.60 mmol), cesium carbonate
(782.0 mg, 2.40 mmol) and aniline (59.0 mg, 0.63 mmol) followed
by toluene (3 mL) and flushed with argon. The reactions were run at
120 or 130 ꢀC for 60, 90 or 180 min (see Tables 2 and 3). After
completion of the reaction the solvent was evaporated and the
residue was purified by column chromatography.
NMR (DMSO-d6, 400 MHz)
1H, J¼1.2, 8.4 Hz), 7.99e7.93 (m, 1H), 7.72e7.60 (m, 2H), 7.19e7.10
(m, 4H); 13C NMR (DMSO-d6, 400 MHz)
158.7, 156.3, 144.2, 143.5,
138.8, 138.7, 136.5, 129.2, 128.5, 127.9, 127.2, 125.1, 120.6, 120.6,
118.4, 116.0, 115.8; C15H10BrFN2 (317.16); LCMS (ESIþ) m/z 317, 319
[MþH]þ. Anal. Calcd for C15H10BrFN2 (317.16) C, 56.81; H, 3.18; N,
8.83. Found: C, 56.65; H, 3.19; N, 8.80.
d 8.68 (s, 1H), 8.13 (br s, 1H), 8.04 (dd,
d
4. 7 . 7 . 4 - B ro m o- 3- ( 4 - m e t h o xy p h e nyla m i no ) qu i n ol i n e
(27c). Prepared from 9 and 26c by irradiation for 60 min. Eluent:
hexane/ethyl acetate (3/2) Yellow oil (129 mg, 65%), 1H NMR (CDCl3,
4.7.1. 4-Bromo-(3-phenylamino)quinoline (22). Prepared from 9.
Eluent: hexane/ethyl acetate (9/1). Green solid (126 mg, 70%), mp
400 MHz)
(d, 2H, J¼8.8 Hz), 6.93 (d, 2H, J¼8.8 Hz), 6.17 (br s, 1H), 3.83 (s, 3H);
13C NMR (CDCl3, 400 MHz)
157.0, 143.3, 141.2, 137.2, 133.4, 129.6,
128.2, 128.2, 126.3, 125.0, 124.4, 115.1, 55.6; C16H13BrN2O (329.20);
LCMS (ESIþ) m/z 329, 331 [MþH]þ. Anal. Calcd for C16H13BrN2O
(329.20) C, 58.38; H, 3.98; N, 8.51. Found: C, 58.21; H, 3.99; N, 8.49.
d 8.64 (s, 1H), 8.05e7.95 (m, 2H), 7.60e7.48 (m, 2H), 7.18
103e105 ꢀC; 1H NMR (DMSO-d6, 400 MHz)
d 8.76 (s, 1H), 8.17 (br s,
1H), 8.06 (dd, 1H, J¼8.4, 8.0 Hz), 8.00e7.96 (m, 1H), 7.72e7.63 (m,
d
2H), 7.29 (t, 2H, J¼8.0 Hz), 7.10 (d, 2H, J¼7.6 Hz), 6.98e6.93 (m, 1H);
13C NMR (DMSO-d6, 400 MHz)
d 145.0, 143.6, 142.5, 136.0, 129.2,
129.1, 128.4, 127.9, 127.3, 125.2, 121.2, 119.6, 117.9; for C15H11BrN2
(299.17); LCMS (ESIþ) m/z 299, 301 [MþH]þ. Anal. Calcd for
C15H11BrN2 (299.17) C, 60.22; H, 3.71; N, 9.36. Found: C, 60.05; H,
3.72; N, 9.33.
4.8. General procedure for the Heck-type reactions
A
microwave vial (2e5 mL) was charged with bis(-
4.7.2. 3-Bromo-(4-phenylamino)quinoline (23). Prepared from 12.
Eluent: dichloromethane (100%). Yellow solid (170 mg, 95%), mp
138e140 ꢀC (lit.,37 mp 136.5e137.5 ꢀC); 1H NMR (DMSO-d6,
triphenylphosphine)palladium(II) dichloride (23.2 mg, 0.03 mmol),
the corresponding phenylaminoquinoline: 22e25 (100 mg,
0.33 mmol) or 27aec (0.33 mmol) and sodium acetate (108.3 mg,
1.32 mmol) followed by N,N-dimethylacetamide (4.8 mL) and
flushed with argon. The reactions were run at 150 ꢀC for 60 or
120 min (see Tables 2 and 3). After completion of the reaction the
solvent was evaporated and the residue was purified by column
chromatography.
400 MHz)
7.79e7.72 (m, 1H), 7.57e7.50 (m, 1H), 7.24e7.16 (m, 2H), 6.91e6.85
(m, 1H), 6.80e6.75 (m, 2H); 13C NMR (DMSO-d6, 400 MHz)
152.7,
d 8.89 (s, 1H), 8.66 (br s, 1H), 8.04e7.95 (m, 2H),
d
147.7, 144.0, 143.3, 129.6, 129.4, 128.7, 126.3, 124.7, 123.7, 120.5, 117.1,
110.7; C15H11BrN2 (299.17); LCMS (ESIþ) m/z 299, 301 [MþH]þ.
Anal. Calcd for C15H11BrN2 (299.17) C, 60.22; H, 3.71; N, 9.36. Found:
C, 60.11; H, 3.71; N, 9.39.
4.8.1. 7H-Indolo[2,3-c]quinoline (4a). Prepared from 22. Eluent:
dichloromethane/methanol (95/5). Yellow solid (42.5 mg, 58%),
mp 253e255 ꢀC (lit.,15 mp 242e244 ꢀC); 1H NMR (DMSO-d6,
4.7.3. 3-Bromo-(2-phenylamino)quinoline (24). Prepared from 17.
Eluent: hexane/ethyl acetate (9/1). Pale pink foam (140 mg, 78%), 1H
400 MHz)
d
12.150 (s, 1H), 9.29 (s, 1H), 8.79 (d, 1H, J¼7.6 Hz), 8.67