D
Synthesis
M. D. L. Tonin et al.
Paper
1
25 [13C, APT (Attached Proton Test)] and 283 MHz (19F), with Varian
um methyltrifluoroborate (2; 122 mg, 1.00 mmol). Purification by
column chromatography (n-hexane/CH Cl , 1:1) afforded 3b.
Unity-300 (600) and AMX 300 instruments in CDCl solutions; chem-
3
2
2
ical shifts (δ) are given in ppm.
Yield: 101 mg (76%); yellow oil.
IR (ATR): 1707, 1585, 1434, 1261, 1135, 727 cm–1
.
1
-(Pyridin-2-yl)-1H-indole (1a); Typical Procedure
1
H NMR (400 MHz, CDCl ): δ = 8.66 (ddd, J = 4.9, 2.0, 0.9 Hz, 1 H), 7.90
3
A mixture of 1H-indole (3.52 g, 30 mmol) and KOH (4.21 g, 75 mmol)
in DMSO (30 mL) was stirred and heated at 120 °C for 15 min, then 2-
bromopyridine (6.64 g, 42 mmol) was added. After 30 h, the mixture
was cooled to ambient temperature, diluted with EtOAc (120 mL) and
(dd, J = 7.6, 1.0 Hz, 1 H), 7.87 (ddd, J = 8.0, 7.5, 2.0 Hz, 1 H), 7.54 (dt, J =
8
1
.2, 0.9 Hz, 1 H), 7.36 (dt, J = 8.0, 1.0 Hz, 1 H), 7.32 (ddd, J = 7.5, 4.9,
.0 Hz, 1 H), 7.14 (dd, J = 8.2, 7.6 Hz, 1 H), 7.09 (t, J = 0.9 Hz, 1 H), 3.99
(s, 3 H), 2.48 (d, J = 1.0 Hz, 3 H).
washed with H O (3 × 50 mL). The product was extracted with EtOAc
2
13
C NMR (100 MHz, CDCl ): δ = 168.1 (C ), 151.0 (C ), 149.8 (CH),
(3 × 100 mL), the organic layer was dried over Na SO , and the solvent
3
q
q
2
4
1
1
1
39.4 (C ), 138.4 (CH), 138.1 (C ), 128.6 (C ), 124.0 (CH), 122.4 (CH),
was removed in vacuo. The crude product was purified by chromatog-
raphy on silica gel (n-hexane/EtOAc, 20:1) to afford 1a.
q
q
q
21.1 (CH), 120.8 (CH), 120.6 (C ), 115.1 (CH), 104.5 (CH), 51.8 (CH ),
q
3
4.0 (CH3).
Yield: 5.36 g (92%); yellow oil.
IR (ATR): 3052, 1587, 1470, 1449, 1433, 1317, 1240, 729 cm–1
+
MS (EI): m/z (%) = 266 (100) [M] , 207 (67).
.
HRMS (EI): m/z [M + H]+ calcd for C16H14N O : 266.1055; found:
1
2
2
H NMR (300 MHz, CDCl ): δ = 8.57 (ddd, J = 4.9, 2.0, 0.8 Hz, 1 H), 8.23
3
266.1053.
(d, J = 8.3 Hz, 1 H), 7.81 (ddd, J = 8.2, 7.4, 2.0 Hz, 1 H), 7.73 (d, J =
3
7
6
.5 Hz, 1 H), 7.66 (dd, J = 7.7, 1.2 Hz, 1 H), 7.48 (d, J = 8.2 Hz, 1 H),
.33–7.27 (m, 1 H), 7.22–7.19 (m, 1 H), 7.15 (dd, J = 7.4, 4.9 Hz, 1 H),
.72 (dd, J = 3.5, 0.9 Hz, 1 H).
5
-Methoxy-2-methyl-1-(pyridin-2-yl)-1H-indole (3c)
The representative procedure was followed using 5-methoxy-1-(pyri-
din-2-yl)-1H-indole (1c; 112 mg, 0.50 mmol) and potassium methyl-
trifluoroborate (2; 122 mg, 1.00 mmol). Purification by column chro-
matography (n-hexane/EtOAc/CH Cl , 10:1:1) afforded 3c.
13
C NMR (125 MHz, CDCl ): δ = 152.0 (C ), 148.4 (CH), 137.9 (CH),
3
q
134.7 (C ), 130.1 (C ), 125.6 (CH), 122.8 (CH), 121.0 (CH), 119.5 (CH),
q q
2
2
1
13.9 (CH), 113.0 (CH), 112.9 (CH), 105.2 (CH).
+
Yield: 89.0 mg (75%); light-brown oil.
IR (ATR): 1588, 1470, 1435, 1372, 907, 781, 728 cm–1
MS (EI): m/z (%) = 194 (100) [M] , 167 (30).
+
HRMS (EI): m/z [M] calcd for C13H10N : 194.0844; found: 194.0841.
2
1
H NMR (300 MHz, CDCl ): δ = 8.53 (ddd, J = 4.9, 2.0, 0.8 Hz, 1 H), 7.74
3
The analytical data are in accordance with those reported in the liter-
12b
(td, J = 7.8, 2.0 Hz, 1 H), 7.28 (dt, J = 8.1, 1.0 Hz, 1 H), 7.20 (d, J = 9.1 Hz,
ature.
1
2
3
H), 7.18–7.14 (m, 1 H), 6.93 (d, J = 2.5 Hz, 1 H), 6.68 (dd, J = 8.9,
.5 Hz, 1 H), 6.25 (q, J = 1.0 Hz, 1 H), 3.75 (s, 3 H), 2.35 (d, J = 1.0 Hz,
H).
2
-Methyl-1-(pyridin-2-yl)-1H-indole (3a)
A suspension of 1-(pyridin-2-yl)-1H-indole (1a; 97.1 mg, 0.50 mmol),
RuCl (p-cymene)]2 (15.3 mg, 5.0 mol%), AgSbF6 (34.4 mg, 20 mol%),
AgF (127 mg, 1.00 mmol) and potassium methyltrifluoroborate (2;
22 mg, 1.00 mmol) in DCE (1.0 mL) was stirred and heated at 120 °C
13
C NMR (100 MHz, CDCl ): δ = 154.9 (C ), 151.6 (C ), 149.5 (CH),
3
q
q
[
2
1
1
38.3 (CH), 137.5 (C ), 132.3 (C ), 129.4 (C ), 121.7 (CH), 120.9 (CH),
11.2 (CH), 111.1 (CH), 103.4 (CH), 102.1 (CH), 55.9 (CH ), 14.2 (CH ).
q q q
3
3
1
+
MS (EI) m/z (%) = 238 (100) [M] , 223 (54).
for 20 h. At ambient temperature, the reaction mixture was diluted
with H O (10.0 mL) and extracted with EtOAc (3 × 25 mL), and the
HRMS (EI): m/z [M + H]+ calcd for C15H14N O: 238.1106; found:
2
2
combined organic layers were dried with Na SO . After filtration and
238.1099.
2
4
evaporation of the solvents in vacuo, the crude product was purified
The analytical data are in accordance with those reported in the liter-
ature.
by column chromatography (n-hexane/EtOAc/CH Cl , 26:3:1) to af-
8c
2
2
ford 3a.
Yield: 86.5 mg (83%); yellow oil.
IR (ATR): 3052, 1581, 1468, 1455, 1432, 776, 734 cm–1
2
,5-Dimethyl-1-(pyridin-2-yl)-1H-indole (3d)
.
The representative procedure was followed using 5-methyl-1-(pyri-
din-2-yl)-1H-indole (1d; 104 mg, 0.50 mmol) and potassium methyl-
trifluoroborate (2; 122 mg, 1.00 mmol). Purification by column chro-
1
H NMR (600 MHz, CDCl ): δ = 8.66–8.65 (m, 1 H), 7.87–7.84 (m, 1 H),
3
7
7
0
.56–7.54 (m, 1 H), 7.41 (dd, J = 8.0, 0.9 Hz, 1 H), 7.39–7.34 (m, 1 H),
.29 (ddd, J = 7.5, 4.9, 0.8 Hz, 1 H), 7.14–7.11 (m, 2 H), 6.42 (dd, J = 0.9,
.9 Hz, 1 H), 2.46 (d, J = 0.9 Hz, 3 H).
matography (n-hexane/EtOAc/CH Cl , 20:1:1) afforded 3d.
2 2
Yield: 72.2 mg (65%); brown oil.
IR (ATR): 1469, 1433, 1202, 1173, 1033, 770, 727 cm–1
13
C NMR (125 MHz, CDCl ): δ = 151.3 (C ), 149.4 (CH), 138.0 (CH),
3
q
.
1
37.0 (C ), 136.7 (C ), 128.6 (C ), 121.7 (CH), 121.4 (CH), 120.7 (CH),
q q q
1
H NMR (300 MHz, CDCl ): δ = 8.63 (ddd, J = 4.9, 2.0, 0.8 Hz, 1 H), 7.83
3
1
20.5 (CH), 119.6 (CH), 110.1 (CH), 103.2 (CH), 14.0 (CH3).
(td, J = 7.7, 2.0 Hz, 1 H), 7.39 (dd, J = 8.0, 1.0 Hz, 1 H), 7.35–7.32 (m,
+
MS (EI): m/z (%) = 208 (100) [M] , 130 (30).
1
H), 7.30–7.22 (m, 2 H), 6.94 (dd, J = 8.4, 1.7 Hz, 1 H), 6.34 (t, J =
HRMS (EI): m/z [M + H]+ calcd for C14H12N : 209.1073; found:
1.0 Hz, 1 H), 2.45 (d, J = 1.0 Hz, 3 H), 2.43 (s, 3 H).
2
209.1079.
13
C NMR (100 MHz, CDCl ): δ = 151.7 (C ), 149.6 (CH), 138.2 (CH),
3
q
The analytical data are in accordance with those reported in the liter-
ature.
137.0 (C
q
), 135.6 (C
q
), 130.0 (C ), 129.1 (C ), 123.1 (CH), 121.7 (CH),
q
q
8c
120.6 (CH), 119.7 (CH), 110.0 (CH), 103.1 (CH), 21.5 (CH ), 14.2 (CH ).
3
3
+
MS (EI) m/z (%) = 222 (100) [M] , 207 (18).
Methyl 2-Methyl-1-(pyridin-2-yl)-1H-indole-4-carboxylate (3b)
HRMS (EI): m/z [M + H]+ calcd for C15H14N : 222.1157; found:
2
The representative procedure was followed using methyl 1-(pyridin-
222.1152.
2-yl)-1H-indole-4-carboxylate (1b; 126 mg, 0.50 mmol) and potassi-
©
Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–H