The Journal of Organic Chemistry
NOTE
J = 8.0 Hz), 4.07 (s, 3 H). 13C NMR (100 MHz): δ 155.8, 150.7, 149.5,
147.5, 146.2, 131.1, 130.5, 130.2, 125.4, 121.0, 120.5, 104.1, 55.9. HRMS
(ES pos): m/z calcd for C15H13N2O+ (M + H+) 237.1022, found
237.1031.
(m, 1 H), 7.41 (m, 2 H), 7.17 (m, 1 H), 6.88 (d, 1 H, J = 1.3, 8.2 Hz), 4.01
(d, 3 H, J = 1.2 Hz). 13C NMR (100 MHz): δ 154.6, 150.0, 145.4, 140.3,
131.0, 128.4, 126.5, 126.5, 125.7, 125.6, 120.9, 120.3, 104.3, 55.8. HRMS
(ES pos): m/z calcd for C14H12NOS+ (M + H+) 242.0634, found
242.0642.
2-(5-Methoxyquinolin-8-yl)isonicotinamide (8). The general proce-
dure above was followed, using 8-bromo-5-methoxyquinoline (200 mg,
0.84 mmol), pinacol bis(pinacolato)diboron (256 mg, 1.01 mmol),
Pd2(dba)3 (7.7 mg, 8.4 μmol), n-BuPAd2 (9.0 mg, 25.2 μmol), KOAc
(247 mg, 2.52 mmol), and DMAc (1 mL). After the reaction was
determined to be complete by HPLC, the reaction mixture was further
treated with degassed aqueous K2CO3 (4 M, 0.84 mL, 3.36 mmol) and
2-bromoisonicotinamide (202 mg, 1.0 mmol). Column chromatography
on silica gel (eluting with 20% EtOAc/hexanes) afforded the product 8
as a pale yellow solid (213 mg, 90%). 1H NMR (400 MHz, DMSO-d6):
δ 9.98 (dd, 1 H, J = 1.8, 4.2 Hz), 8.81 (d, 1 H, J = 4.0 Hz), 8.65 (dd, 1 H,
J = 1.6, 8.4 Hz), 8.50 (bs, 1 H), 8.23 (s, 1 H), 8.13 (d, 1 H, J = 8.2 Hz), 7.73
(dd, 1 H, J = 1.6, 6.7 Hz), 7.70 (bs, 1 H), 7.60 (dd, 1 H, J = 4.1, 8.5 Hz),
7.24 (d, 1 H, J = 8.4 Hz), 4.07 (s, 3 H). 13C NMR (100 MHz, DMSO-
d6): δ 166.9, 157.1, 155.3, 150.7, 149.6, 145.6, 140.7, 131.6, 130.6, 130.0,
124.4, 120.7, 119.8, 119.2, 104.9, 56.1. HRMS (ES pos): m/z calcd for
C16H14N3O2+ (M + H+) 280.1080, found 280.1085.
5-Methoxy-8-o-tolylquinoline (12). The general procedure above
was followed, using 8-bromo-5-methoxyquinoline (200 mg, 0.84 mmol),
pinacol bis(pinacolato)diboron (256 mg, 1.01 mmol), Pd2(dba)3 (7.7
mg, 8.4 μmol), n-BuPAd2 (9.0 mg, 25.2 μmol), KOAc (247 mg,
2.52 mmol), and DMAc (1 mL). After the reaction was determined to
be complete by HPLC, the reaction mixture was further treated with
degassed aqueous K2CO3 (4 M, 0.84 mL, 3.36 mmol) and 1-bromo-2-
methylbenzene (171 mg, 1.0 mmol). Column chromatography on silica
gel (eluting with 10% EtOAc/hexanes) afforded the product 12 as a solid
(182 mg, 87%). 1H NMR (400 MHz, CDCl3): δ 8.88 (m 1 H), 8.61 (m,
1 H), 7.47 (d, 1 H, J = 7.8 Hz), 7.35ꢀ7.28 (m, 5 H), 6.89 (d, 1 H, J = 8.0
Hz), 4.0 (s, 3 H), 2.04 (s, 3 H). 13C NMR (100 MHz): δ 154.7, 150.6,
147.2, 140.1, 137.4, 133.6, 130.8, 130.6, 130.2, 129.8, 127.5, 125.5, 120.8,
120.0, 103.9, 55.8, 20.6. HRMS (ES pos): m/z calcd for C17H16NO+ (M
+ H+) 250.1226, found 250.1230.
8-Phenylquinoline (14). The general procedure above was followed,
using 8-chloroquinoline (200 mg, 1.22 mmol), pinacol bis(pinacolato)-
diboron (373 mg, 1.47 mmol), Pd2(dba)3 (11.2 mg, 12.2 μmol), n-
BuPAd2 (13.1 mg, 36.7 μmol), KOAc (360 mg, 3.67 mmol), and DMAc
(1 mL). After the reaction was determined to be complete by HPLC, the
reaction mixture was further treated with degassed aqueous K2CO3 (4
M, 0.84 mL, 3.36 mmol) and bromobenzene (230 mg, 1.47 mmol).
Column chromatography on silica gel (eluting with 10% EtOAc/
hexanes) afforded the product 14 as a pale yellow oil (233 mg,
93%). 1H NMR (400 MHz, CDCl3): δ 8.89 (dd, 1 H, J = 1.8,
4.2 Hz), 8.03 (dd, 1 H, J = 1.7, 8.3 Hz), 7.70ꢀ7.64 (m, 4 H),
7.49ꢀ7.43 (m, 3 H), 7.36 (m, 1H), 7.24 (m, 1 H). 13C NMR (100
MHz): δ 150.4, 146.2, 141.0, 139.8, 136.4, 130.9, 130.5, 128.9, 128.2,
127.7, 127.6, 126.4, 121.1. HRMS (ES pos): m/z calcd for C15H12N+
(M + H+) 206.0964, found 206.0975.
Methyl 5-(5-Methoxy quinolin-8-yl)furan-2-carboxylate (9). The
general procedure above was followed, using 8-bromo-5-methoxyquino-
line (200 mg, 0.84 mmol), pinacol bis(pinacolato)diboron (256 mg,
1.01 mmol), Pd2(dba)3 (7.7 mg, 8.4 μmol), n-BuPAd2 (9.0 mg, 25.2
μmol), KOAc (247 mg, 2.52 mmol), and DMAc (1 mL). After the
reaction was determined to be complete by HPLC, the reaction mixture
was further treated with 9% degassed aqueous NaHCO3 (3.14 g, 3.36
mmol) and methyl 5-bromo-2-fumorate (205 mg, 1.0 mmol). Column
chromatography on silica gel (eluting with 10% EtOAc/hexanes)
afforded the product 9 as a solid (213 mg, 85%). 1H NMR (400
MHz, DMSO-d6): δ 9.05 (m, 1H), 8.62 (dd, 1 H, J = 1.8, 8.5 Hz), 8.23
(d, 1 H, J = 8.4 Hz), 7.76 (d, 1 H, J = 3.6 Hz), 7.63 (dd, 1 H, J = 4.2, 8.5
Hz), 7.46 (d, 1 H, J = 3.6 Hz), 7.23 (d, 1 H, J = 8.4 Hz), 4.06 (s, 3 H), 3.87
(s, 3 H); 13C NMR (100 MHz, DMSO-d6): δ 158.5, 155.4, 154.7, 151.0,
144.5, 141.7, 130.8, 127.9, 121.1, 120.5, 120.1, 119.1, 112.7, 105.1, 56.2,
51.7. HRMS (ES pos): m/z calcd for C16H14NO4+ (M + H+) 284.0917,
found 284.0932.
6-Methoxy-9-methyl-5-phenyl-3,4-dihydroacridin-1(2H)-one (16).
The general procedure above was followed, using 5-bromo-6-meth-
oxy-9-methyl-3,4-dihydroacridin-1(2H)-one (269 mg, 0.84 mmol),
pinacol bis(pinacolato)diboron (256 mg, 1.01 mmol), Pd2(dba)3 (7.7
mg, 8.4 μmol), n-BuPAd2 (9.0 mg, 25.2 μmol), KOAc (247 mg, 2.52
mmol), and DMAc (1 mL). After the reaction was determined to be
complete by HPLC, the reaction mixture was further treated with
degassed aqueous K2CO3 (4 M, 0.84 mL, 3.36 mmol) and bromoben-
zene (160 mg, 1.0 mmol). Column chromatography on silica gel (eluting
with 10% EtOAc/hexanes) afforded the product 16 as a solid (258 mg,
5,50-Dimethoxy-8,80-biquinoline (10). The general procedure above
was followed, using 8-bromo-5-methoxyquinoline (200 mg, 0.84 mmol),
pinacol bis(pinacolato)diboron (256 mg, 1.01 mmol), Pd2(dba)3
(7.7 mg, 8.4 μmol), n-BuPAd2 (9.0 mg, 25.2 μmol), KOAc (247 mg,
2.52 mmol) and DMAc (1 mL). After the reaction was determined to be
complete by HPLC, the reaction mixture was further treated with
degassed aqueous K2CO3 (4 M, 0.84 mL, 3.36 mmol) and 8-bromo-
5-methoxyquinoline (238 mg, 1.0 mmol). Column chromatography on
silica gel (eluting with 30% EtOAc/hexanes) afforded the product 10 as
a solid (258 mg, 98%). 1H NMR (400 MHz, DMSO-d6): δ 8.65 (d, 1 H,
J = 2.3 Hz), 8.59 (d, 1 H, J = 8.5 Hz), 7.63 (d, 1 H, J = 7.9 Hz), 7.46 (m,
1H), 7.15 (d, 1H, J = 7.8 Hz), 4.1 (s, 3H). 13C NMR (100 MHz, DMSO-
d6): δ 154.0, 149.8, 147.5, 131.4, 131.1, 130.0, 120.2, 119.7, 104.3, 55.9.
1
73%). H NMR (400 MHz, CDCl3): δ 8.23 (d, 1 H, J = 9.44 Hz),
7.47ꢀ7.25 (m, 6 H), 3.91 (s, 3 H), 3.07ꢀ3.05 (m, 5H), 2.73 (t, 2 H, J =
8.0 Hz), 2.10 (t, 2 H, J = 8.0 Hz). 13C NMR (100 MHz, CDCl3): δ 200.9,
162.6, 158.3, 149.5, 147.3, 135.0, 131.9, 127.3, 126.8, 126.5, 125.9, 123.4,
122.8, 113.2, 56.4, 41.2, 35.2, 21.4, 16.2. HRMS (ES pos): m/z calcd for
C21H20NO2+ (M + H+): 318.1488, found 318.1489.
+
HRMS (ES pos): m/z calcd for C20H17N2O2 (M + H+): 317.1284,
2-Methyl-8-phenylquinoline (18). The general procedure above was
followed, using 8-bromo-2-methylquinoline (187 mg, 0.84 mmol),
pinacol bis(pinacolato)diboron (256 mg, 1.01 mmol), Pd2(dba)3
(7.7 mg, 8.4 μmol), n-BuPAd2 (9.0 mg, 25.2 μmol), KOAc (247 mg,
2.52 mmol), and DMAc (1 mL). After the reaction was determined to
be complete by HPLC, the reaction mixture was further treated with
degassed aqueous K2CO3 (4 M, 0.84 mL, 3.36 mmol) and bromoben-
zene (160 mg, 1.0 mmol). Column chromatography on silica gel (eluting
with 10% EtOAc/hexanes) afforded the product 18 as a pale yellow oil
(179 mg, 97%). 1H NMR (400 MHz, DMSO-d6): δ 8.04 (d,
1 H, J = 8.4 Hz), 7.79ꢀ7.69 (m, 4 H), 7.52ꢀ7.45 (m, 3 H), 7.40ꢀ7.36 (m,
1 H), 7.26 (d, 1 H, J = 8.4 Hz), 2.67 (s, 3 H). 13C NMR (100 MHz,
DMSO-d6): δ 158.7, 145.5, 139.9, 140.0, 136.2, 131.1, 130.3, 127.8,
found 317.1292.
5-Methoxy-8-(thiophen-2-yl)quinoline (11). The general procedure
above was followed, using 8-bromo-5-methoxyquinoline (200 mg, 0.84
mmol), pinacol bis(pinacolato)diboron (256 mg, 1.01 mmol), Pd2-
(dba)3 (7.7 mg, 8.4 μmol), n-BuPAd2 (9.0 mg, 25.2 μmol), KOAc
(247 mg, 2.52 mmol), and DMAc (1 mL). After the reaction was
determined to be complete by HPLC, the reaction mixture was further
treated with degassed aqueous K2CO3 (4 M, 0.84 mL, 3.36 mmol) and
2-bromothiophene (163 mg, 1.0 mmol). Column chromatography on
silica gel (eluting with 10% EtOAc/hexanes) afforded the product 11 as
a solid (258 mg, 85%). 1H NMR (400 MHz, CDCl3): δ 9.00 (dd 1 H, J =
1.8, 4.2 Hz), 8.61 (dd, 1 H, J = 1.8, 8.4 Hz), 7.94 (d, 1 H, J = 8.2 Hz), 7.65
6398
dx.doi.org/10.1021/jo200904g |J. Org. Chem. 2011, 76, 6394–6400