James et al.
(o), 123.6 (o), 122.3 (o), 122.1 (o), 121.0 (e), 119.9 (o), 111.0 (o),
56.1 (o), 43.1 (e), 39.2 (o), 13.6 (o), 12.0 (o); MS (EI (70 eV)) m/e
(rel intensity) 356 (M+, 100), 340 (16), 283 (58), 268 (17), 195
(7.5); HRMS (EI (70 eV)) m/e calcd for C20H22NO3S 356.1321,
found 356.1326.
dt, J ) 7.9, 1.2 Hz, 1H), 7.64 (app dt, J ) 7.6, 0.76 Hz, 1H), 7.50
(dd, J ) 8.2, 8.0 Hz, 1H), 7.39 (dd, J ) 8.2, 1.0 Hz); 13C NMR
(50 MHz, DMF-d7) δ 157.8 (e), 153.3 (e), 148.4 (e), 142.3 (e),
139.5 (e), 130.8 (o), 128.1 (e), 126.1 (o), 125.8 (o), 124.3 (o), 123.1
(e), 118.0 (e), 116.6 (o), 113.7 (o), 113.2 (o), 56.6 (o); MS (EI (70
eV)) m/e (rel intensity) 266 (M+, 18), 223 (8.7), 195 (8.7), 167
(19), 152 (16), 139 (95), 125 (12), 113 (100). Anal. Calcd for
C16H10O4: C, 72.18; H, 3.79. Found: C, 72.33; H, 3.71.
4-Methoxy-4H-thianaphtheno[2,3-c]benzo[e]pyran-6-one (22b).
According to general procedure D, a solution of the corresponding
hydroxy amide (0.190 g, 0.536 mmol) in HOAc (10 mL) was heated
at reflux for 10 min. Standard workup followed by recrystallization
(CH2Cl2/hexane) afforded the title compound (0.143 g, 95%) as
light yellow needles: mp 206-207 °C (dec) (CH2Cl2/hexane); IR
N-tert-Butoxycarbonylindole-2-boronic acid (17c). To a solu-
tion of N-tert-butoxycarbonylindole36 (1.03 g, 4.75 mmol) in THF
(20 mL) at -78 °C was added t-BuLi (4.00 mL, 1.66 mol/L)
dropwise over 10 min. The reaction mixture was allowed to stir
for 1 h, and B(OMe)3 (1.35 mL, 11.9 mmol) was added quickly.
The solution was allowed to warm to rt over 6 h, quenched with
saturated NH4Cl, and subjected to standard workup to afford the
crude boronic acid (0.853 g), which was unstable and used without
(KBr) ν (max) 3013, 2928, 2824, 1720, 1605, 1585, 1449 cm-1
;
1H NMR (500 MHz, DMF-d7) δ 8.89 (d, J ) 7.95 Hz, 1H),
8.34-8.29 (m, 2H), 7.78-7.71 (m, 2H), 7.41 (app t, J ) 8.3 Hz,
1H), 7.39 (d, J ) 7.4 Hz, 1H), 4.03 (s, 3H); 13C NMR (62.9 MHz,
DMF-d7) δ 157.7 (e), 148.6 (e), 143.7 (e), 142.8 (e), 139.4 (e),
135.6 (e), 129.3 (e), 127.1 (e), 126.8 (o), 126.5 (e), 125.6 (o), 124.5
(o), 119.1 (e), 115.9 (o), 113.3 (o), 56.6 (o); MS (EI (70 eV)) m/e
(rel intensity) 282 (M+, 100), 239 (26), 224 (3.1), 211 (14), 195
(6.2), 183 (20), 139 (26). Anal. Calcd for C16H10O3S: C, 68.07; H,
3.57. Found: C, 67.84; H, 3.70.
1
further purification: H NMR (250 MHz, CDCl3) δ 8.02 (d, J )
8.5 Hz, 1H), 7.61 (d, J ) 7.4 Hz, 1H), 7.50 (s, 1H), 7.42 (s, 2H,
exch), 7.36 (app dt, J ) 7.3, 1.3 Hz, 1H), 7.26 (app dt partially
obscured by solvent), 1.74 (s, 9H).
N,N-Diethyl O-[2-(N-tert-butoxycarbonyl-2-indolyl)-6-meth-
oxy]phenylcarbamate (18e). According to general procedure G,
a mixture of N,N-diethyl O-(2-iodo-6-methoxy)phenylcarbamate
(0.710 g, 2.03 mmol), N-tert-butoxycarbonylindole-2-boronic acid
(0.6081 g, 2.332 mmol), Pd(PPh3)4 (0.100 g, 0.0865 mmol), and
Na2CO3 (10 mL, 2 mol/L) in DME (20 mL) was heated for 1.5 h.
Standard workup followed by column chromatography (5:1 hexane/
EtOAc) and recrystallization (hexane/CH2Cl2) afforded the title
compound (0.477 g, 54%) as colorless needle-plates: mp 123-124
°C (hexane/CH2Cl2); IR (CH2Cl2) ν (max) 2920, 1727, 1577, 1474,
N,N-Diethyl O-[2-(3-benzofuranyl)-6-methoxy]phenylcarbam-
ate (21a). Procedure 1: According to general procedure G, a
mixture of 3-bromobenzofuran35 (1.11 g, 5.19 mmol), 2-N,N-
diethylcarbamato-3-methoxyphenylboronic acid (16a) (1.82 g, 6.82
mmol), Pd(PPh3)4 (0.120 g, 0.104 mmol), and Cs2CO3 (20 mL, 2
mol/L) was heated at reflux for 12 h. Standard workup followed
by purification by column chromatography (5:1 f 4:1 hexane/
EtOAc) and distillation afforded the title compound (0.591 g, 34%)
as a colorless oil: bp 155-160 °C/0.3 mmHg (Kugelrohr); IR (neat)
1
1
3028, 2975, 2936, 2839, 1718, 1611, 1578, 1453, 1417 cm-1; H
1418 cm-1; H NMR (250 MHz, CDCl3) δ 8.24 (d, J ) 8.4 Hz,
NMR (250 MHz, CDCl3) δ 7.34 (s, 1H), 7.69 (m, 1H), 7.52 (m,
1H), 7.16 (dd, J ) 7.8, 1.7 Hz, 1H), 6.96 (dd, J ) 7.8, 1.7 Hz,
1H), 3.85 (s, 3H), 3.27 (q, J ) 7.3 Hz, 4H), 1.08 (t, J ) 7.3 Hz,
3H), 0.99 (t, J ) 7.3 Hz, 3H); 13C NMR (62.9 MHz, CDCl3) δ
155.1 (e), 153.6 (e), 152.6 (e), 142.7 (o), 138.5 (e), 127.2 (e), 126.4
(e), 125.8 (o), 124.2 (o), 122.7 (o), 121.9 (o), 120.8 (o), 117.3 (e),
111.7 (o), 111.3 (o), 56.0 (o), 42.0 (e), 41.8 (e), 13.7 (o), 13.2 (o);
MS (EI (70 eV)) m/e (rel intensity) 339 (M+, 100), 324 (1.9), 285
(1.9), 267 (3.7), 239 (8.6), 239 (9.0), 196 (5.6), 168 (10), 100 (77),
72 (23); HRMS (EI (70 eV)) m/e calcd for C20H21NO4 339.1471,
found 339.1484.
1H), 7.51 (dd, J ) 7.0, 0.8 Hz, 1H), 7.29 (ddd, J ) 8.4, 7.4, 1.5
Hz, 1H), 7.19 (ddd, J ) 7.6, 7.4, 1.2 Hz, 1H), 7.17 (app t, J ) 8.0
Hz, 1H), 7.00-6.95 (m, 2H), 6.58 (d, J ) 0.5 Hz, 1H), 3.82 (s,
3H), 3.19-3.11 (m, 4H), 1.27 (s, 9H), 0.94-0.88 (m, 6H); 13C
NMR (62.9 MHz, CDCl3) δ 152.7 (e), 151.9 (e), 149.7 (e), 138.6
(e), 136.8 (e), 135.1 (e), 130.1 (e), 128.9 (e), 125.2 (o), 123.9 (o),
122.3 (o), 121.8 (o), 120.3 (o), 114.8 (o), 112.1 (o), 110.2 (o), 82.6
(e), 56.0 (o), 42.1 (e), 41.4 (e), 27.3 (o), 13.4 (o), 12.7 (o); MS (EI
(70 eV)) m/e (rel intensity) 438 (M+, 15), 338 (16), 265 (14), 238
(5.0), 195 (3.5), 100 (100), 72 (25). Anal. Calcd for C25H30N2O5:
C, 68.47; H, 6.90; N, 6.39. Found: C, 68.43; H, 6.86; N, 6.45.
4-Methoxy-6H-indolo[3,2-c]benzo[e]pyran-6-one (19e). To a
solution of LDA (0.811 mmol) in THF (5 mL) at -78 °C was
added a solution of carbamate 18e (0.107 g, 0.244 mmol) in THF
(4 mL) via canula. The resulting solution was allowed to warm to
rt over 12 h, and subsequent standard workup afforded the crude
hydroxy amide which was cyclized according to general procedure
D (10 mL of HOAc). After heating at reflux for 1 h, the cooled
solution was diluted with H2O (10 mL) and cooled in an ice bath.
The mixture was filtered, and the precipitate was washed with cold
HOAc/H2O (1:1), affording the title compound (0.0538 g, 83%):
mp 289-296 °C dec; IR (KBr) ν (max) 3365, 3070, 2981, 1685,
1623, 1593, 1515, 1465 cm-1; 1H NMR (500 MHz, DMSO) δ 12.98
(s, 1H), 8.03 (d, J ) 7.6 Hz, 1H), 7.75 (d, J ) 7.9 Hz, 1H), 7.65
(d, J ) 8.1 Hz, 1H), 7.42-7.40 (m, 1H), 7.39 (d, J ) 7.9 Hz, 1H),
7.33 (app t, J ) 7.6 Hz, 1H), 7.29 (d, J ) 8.1 Hz, 1H), 3.94 (s,
3H); 13C NMR (62.9 MHz, CDCl3) δ poor solubility did not allow
acquisition of a satisfactory 13C spectrum; MS (EI (70 eV)) m/e
(rel intensity) 265 (M+, 100), 222 (14), 194 (6.2), 166 (6.0), 141
(30), 100 (54); HRMS (EI (70 eV)) m/e calcd for C16H11NO3
265.0739, found 265.0752.
N,N-Diethyl 3-(2-hydroxy-3-methoxyphenyl)benzofuran-2-
carboxamide. According to general procedure H, a solution of
carbamate 21a (0.280 g, 0.827 mmol) in THF (10 mL) was added
to a solution of LDA (2.67 mmol) in THF (5 mL) at 0 °C. The
reaction mixture was allowed to stir for 15 min, and standard
workup followed by column chromatography (2:1 hexane/EtOAc)
afforded the title compound (0.229 g, 82%) as a foam: IR (CH2Cl2)
1
ν (max) 3518, 3057, 292937, 1614, 1573, 1470 cm-1; H NMR
(250 MHz, CDCl3) δ 8.69 (s, 1H, exch), 7.54-7.59 (m, 2H), 7.38
(ddd, J ) 8.2, 7.4, 1.2 Hz, 1H), 7.27-7.21 (m, 1H), 7.01-6.90
(m, 3H), 3.89 (s, 3H), 3.49 (q, J ) 7.1 Hz, 2H), 3.37 (q, J ) 7.1
Hz, 2H), 1.18 (t, J ) 7.1 6H); 13C NMR (62.9 MHz, CDCl3) δ
162.5 (e), 153.6 (e), 149.4 (e), 144.4 (e), 144.0 (e), 128.2 (e), 126.2
(o), 123.2 (o), 123.0 (o), 122.4 (o), 121.9 (o), 119.8 (o), 118.9 (e),
111.4 (o), 55.9 (o), 43.2 (e), 40.4 (e), 14.0 (o), 12.4 (o); HRMS
(EI (70 eV)) m/e calcd for C20H22NO4 340.1549, found 340.1558.
4-Methoxy-6H-benzofurano[2,3-c]benzo[e]pyran-6-one (22a).
According to general procdure D, a solution of the corresponding
hydroxy amide (0.229 g, 0.676 mmol) in HOAc (10 mL) was heated
at reflux for 10 min. Standard workup followed by recrystallization
(CH2Cl2/hexane) afforded the title compound (0.154 g, 86%) as a
light yellow powder: mp 222-228 °C dec (CH2Cl2/hexane); IR
(KBr) ν (max) 3073, 3011, 2934, 1731, 1614, 1564, 1468, 1444
cm-1; 1H NMR (250 MHz, acetone-d6) δ 8.60 (d, J ) 7.9 Hz, 1H),
8.06 (dd, J ) 8.0, 1.0 Hz, 1H), 7.95 (d, J ) 8.5 Hz, 1H), 7.81 (app
N-tert-Butoxycarbonyl-3-bromoindole (20c). A solution of
N-tert-butoxycarbonylindole (1.06 g, 4.89 mmol) and NBS (0.920
g, 5.17 mmol) in CH2Cl2 (50 mL) was heated at reflux for 2 h, and
the cooled reaction mixture was diluted with H2O (50 mL). The
layers were separated, and the organic phase was washed (10%
(35) Baciocchi, E.; Sebastiani, G. V. J. Org. Chem. 1979, 44, 28.
(36) Grehn, L.; Ragnarsson, U. Angew. Chem., Int. Ed. Engl. 1984, 23, 296.
4102 J. Org. Chem. Vol. 74, No. 11, 2009