B. Dassonneville, B. Witulski, H. Detert
FULL PAPER
C2 9 H2 6 N2 NaO7 S [M + Na]+ 569.1353; found 569.1373.
C29H26N2O7S (546.59): calcd. C 63.72, H 4.79, N 5.13; found C
64.27, H 5. 04, N 5.03.
a solution of 7b (171 mg, 0.31 mmol) and LiOH (22.5 mg,
0.93 mmol) in THF/H2O (2:1, 15 mL) gave acid 10b (166 mg,
0.31 mmol, 100 %) as a white solid, m.p. 170–171 °C (dec.). 1H
NMR (400 MHz, CDCl3, 25 °C): δ = 9.16 (s, 1 H, 4-H), 9.01 (d,
3JH,H = 8.3 Hz, 1 H, 9-H), 8.48 (d, 3JH,H = 8.4 Hz, 1 H, 6-H), 7.80
(d, JH,H = 8.4 Hz, 2 H, 2-H, 6-H Ts), 7.69 (t, JH,H = 7.4 Hz, 1
H, 7-H), 7.52 (t, 3JH,H = 7.6 Hz, 1 H, 8-H), 7.35 (d, 3JH,H = 3.4 Hz,
1 H, 4-H Fu), 7.32 (d, 3JH,H = 3.4 Hz, 1 H, 3-H Fu), 7.19 (d, 3JH,H
= 8.4 Hz, 2 H, 3-H, 5-H Ts), 2.31 (s, 3 H, CH3 Ts), 1.65 (s, 9 H,
tBu) ppm. 13C NMR (100 MHz, CDCl3, 25 °C): δ = 164.1 (Cq.,
COOH), 157.5 (Cq., COOtBu), 154.2 (Cq., C-2 Fu), 146.7 (Cq., C-
3), 146.1, 146.0 (Cq., C-4 Ts and C-5 Fu), 142.5 (Cq., C-1), 141.1
(Cq., C-4a), 139.4 (Cq., C-5a), 134.1 (Cq., C-1 Ts), 130.1 (CH, C-3,
C-5 Ts), 130.0 (CH, C-7), 126.6 (CH, C-2, C-6 Ts), 125.4 (CH, C-
9), 125.0 (CH, C-8), 122.2 (Cq., C-9a), 121.6 (Cq., C-9b), 118.8 (CH,
C-4 Fu), 114.3 (CH, C-6), 114.2 (CH, C-3 Fu), 108.8 (CH, C-4),
82.7 (Cq., tBu), 28.2 (CH3, tBu), 21.5 (CH3, Ts) ppm. IR (neat,
1-[5-(tert-Butoxycarbonyl)furan-2-yl]-9-tosyl-9H-pyrido[3,4-b]-
indole-3-carboxylic Acid (10a): LiOH (37 mg, 1.54 mmol, 3 equiv.)
was added to a solution of 6a (280.7 mg, 0.514 mmol) in THF/H2O
(15 mL, 2:1) and stirred for 1 h. It was acidified to pH 1–2 with
HCl (5 mL, 1 n), CH2Cl2 (20 mL) and H2O (20 mL) were added,
the layers were separated, and the aqueous layer was extracted with
CH2Cl2 (3ϫ10 mL). The combined organic layers were washed
with brine (20 mL), dried with MgSO4, filtered, and the solvent
was removed in vacuo to give acid 10a as a white solid; m.p. 182–
183 °C (PE/CH2Cl2). 1H NMR (400 MHz, CDCl3, 25 °C): δ = 8.51
3
3
3
3
(s, 1 H, 4-H), 8.15 (d, JH,H = 8.1 Hz, 1 H, 8-H), 7.84 (d, JH,H
=
7.7 Hz, 1 H, 5-H), 7.61 (t, 3JH,H = 8.1 Hz, 1 H, 7-H), 7.42 (t, 3JH,H
= 7.7 Hz, 1 H, 6-H), 7.28 (m, 2 H, 4-H, 3-H Fu), 7.07 (d, JH,H
3
=
3
8.1 Hz, 2 H, 2-H, 6-H Ts), 6.90 (d, JH,H = 8.1 Hz, 2 H, 3-H, 5-H
Ts), 2.21 (s, 3 H, CH3 Ts), 1.65 (s, 9 H, CH3 tBu) ppm. 13C NMR
(100 MHz, CDCl3, 25 °C): δ = 163.9 (Cq., COOH), 157.9 (Cq., CO-
OtBu), 153.9 (Cq., C-2 Fu), 146.3 (Cq., C-4 Ts), 145.3 (Cq., C-5 Fu),
142.8 (Cq., C-1), 141.9 (Cq., C-8), 140.6 (Cq., C-3), 139.2 (Cq., C-
4a), 136.4 (Cq., C-9a), 132.2 (Cq., C-1 Ts), 131.0 (CH, C-7), 129.2
(CH, C-3, C-5 Ts), 126.9 (CH, C-2, C-6 Ts), 126.2 (CH, C-6), 125.9
(Cq., C-4b), 121.8 (CH, C-5), 119.0 (CH, C-8), 118.3 (CH, C-4 Fu),
114.1 (CH, C-4), 112.8 (CH, C-3 Fu), 82.3 (Cq., tBu), 28.2 (CH3,
ATR): ν = 3144, 2977, 1764, 1703, 1587, 1431, 1361, 1300, 1166,
˜
1134, 1021, 961, 745 cm–1. FD-MS: m/z (%) = 531.8 (100) [M]+.
1-[5-(Methoxycarbonyl)furan-2-yl]-5-tosyl-5H-pyrido[4,3-b]indole
(11b): According to the procedure for 11a, decarboxylation/esterifi-
cation of 10b (83.3 mg, 0.156 mmol) led to 11b as a white solid in
72% yield (51 mg, 0.113 mmol); m.p. 193–194 °C (PE/CH2Cl2), Rf
= 0.46 (PE/EtOAc = 2:1), and 4.6 mg (0.016, 10%) of the detosyl-
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ated 12b. 1H NMR (400 MHz, CDCl3, 25 °C): δ = 8.79 (d, JH,H
3
= 8.1 Hz, 1 H, 9-H), 8.66 (d, JH,H = 5.6 Hz, 1 H, 3-H), 8.40 (d,
tBu), 21.3 (CH , Ts) ppm. IR (neat, ATR): ν = 3296, 2976, 1745,
˜
3
3JH,H = 8.5 Hz, 1 H, 6-H), 8.31 (d, 3JH,H = 5.6 Hz, 1 H, 4-H), 7.73
1709, 1590, 1518, 1428, 1347, 1311, 1178, 1138, 930, 761 cm–1. FD-
3
3
MS: m/z (%) = 531.7 (100) [M]+.
(d, JH,H = 8.3 Hz, 2 H, 2-H, 6-H Ts), 7.59 (t, JH,H = 7.6 Hz, 1
H, 7-H), 7.45 (t, 3JH,H = 7.7 Hz, 1 H, 8-H), 7.38 (d, 3JH,H = 3.6 Hz,
1 H, 4-H Fu), 7.30 (d, 3JH,H = 3.6 Hz, 1 H, 3-H Fu), 7.15 (d, 3JH,H
= 8.2 Hz, 2 H, 3-H, 5-H Ts), 3.97 (s, 3 H, OCH3), 2.30 (s, 3 H,
CH3 Ts) ppm. 13C NMR (100 MHz, CDCl3, 25 °C): δ = 159.0 (Cq.,
Fu-COO), 156.8 (Cq., C-2 Fu), 146.3 (CH, C-3), 145.7 (Cq., C-4
Ts), 145.1 (Cq., C-4a), 144.5 (Cq., C-5 Fu), 142.74 (Cq., C-1), 138.43
(Cq., C-5a), 134.5 (Cq., C-1 Ts), 130.0 (CH, C-3, C-5 Ts), 128.8
(CH, C-7), 126.6 (CH, C-2, C-6 Ts), 124.7 (2ϫ CH, C-8, C-9),
123.4 (Cq., C-9a), 119.7 (CH, C-4 Fu), 119.6 (Cq., C-9b), 114.3
(CH, C-6), 113.1 (CH, C-3 Fu), 109.4 (CH, C-4), 52.1 (OCH3),
1-[5-(Methoxycarbonyl)furan-2-yl]-9-tosyl-9H-pyrido[3,4-b]indole
(11a): A solution of 10a (108.9 mg, 0.2 mmol) in Ph2O (5 mL) was
heated in a microwave reactor (300 W, 240 °C, 3 min). Methanol
(10 mL) was added to the cooled solution, and at 0 °C a solution
of CH2N2 in ether was added. After stirring (16 h, 25 °C), residual
CH2N2 was destroyed with AcOH, solvents were removed, and the
residue was dissolved with EtOAc and H2O (20 mL each). The
aqueous layer was extracted with EtOAc (3ϫ20 mL), and the com-
bined organic extracts were washed (2 ϫ 30 mL of NaHCO3,
1ϫ30 mL of brine), dried (MgSO4), filtered, and concentrated. Pu-
rification by column chromatography (SiO2, PE/EtOAc = 2:1, Rf =
0.21), gave the β-carboline 11a as a yellow solid, m.p. 201–202 °C
(PE/CH2Cl2), together with 5.3 mg (0.018 mmol, 9%) of the detos-
ylated β-carboline 12a. 1H NMR (400 MHz, CDCl3, 25 °C): δ =
21.5 (CH , Ts) ppm. IR (neat, ATR): ν = 3136, 3045, 2966, 1725,
˜
3
1431, 1382, 1300, 1177, 1156, 1021, 742 cm–1. FD-MS: m/z (%) =
445.8 (100) [M]+. C24H18N2O5S (446.0936): calcd. C 64.56, H 4.06,
N 6.27; found C 64.52, H 4.07, N 6.28.
1-[5-(Methoxycarbonyl)furan-2-yl]-9H-pyrido[3,4-b]indole (12a): A
solution of 11a (98 mg, 0.22 mmol) and TBAF (1.5 mL of 1.0 m in
THF, 1.5 mmol) in THF (20 mL) was stirred (2 h, 25 °C). After
completion of the reaction (TLC), EtOAc and H2O (10 mL each)
were added, the layers were separated, and the aqueous layer was
extracted with EtOAc (3ϫ10 mL). The pooled organic layers were
washed with brine (20 mL), dried (MgSO4), filtered, and concen-
trated. Purification by column chromatography (SiO2, PE/EtOAc
= 1:1, Rf = 0.54) gave 12a (57.4 mg,0.196 mmol, 89%) as a yellow
solid of m.p. 168–169 °C (PE/CH2Cl2). 1H NMR (400 MHz,
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3
8.68 (d, JH,H = 4.9 Hz, 1 H, 3-H), 8.19 (d, JH,H = 8.4 Hz, 1 H,
3
3
8-H), 7.77 (d, JH,H = 7.8 Hz, 1 H, 5-H), 7.62 (d, JH,H = 4.9 Hz,
3
3
1 H, 4-H), 7.57 (t, JH,H = 7.2 Hz, 1 H, 6-H), 7.39 (d, JH,H
=
3.7 Hz, 1 H, 4-H FuЈ), 7.37 (t, JH,H = 7.6 Hz, 1 H, 7-H), 7.24 (d,
3
3JH,H = 3.5 Hz, 1 H, 3-H Fu), 7.04 (d, JH,H = 8.4 Hz, 2 H, 2-H,
3
3
6-H, Ts), 6.88 (d, JH,H = 8.0 Hz, 3-H, 5-H Ts), 3.96 (s, 3 H,
OCH3), 2.20 (s, 3 H, CH3 Ts) ppm. 13C NMR (100 MHz, CDCl3,
25 °C): δ = 159.2 (Cq., Fu-COO), 156.4 (Cq., C-2 Fu), 145.4 (CH,
C-3), 144.7 (Cq., C-4 Ts), 144.3 (Cq., C-5 Fu), 142.2 (Cq., C-8a),
140.5 (Cq., C-1), 138.7 (Cq., C-4a), 134.1 (Cq., C-9a), 132.21 (Cq.,
C-1 Ts), 130.1 (CH, C-7), 128.9 (CH, C-3, C-5 Ts), 127.0 (CH, C-
2, C-6 Ts), 126.7 (Cq, C-4b), 125.8 (CH, C-6), 121.2 (CH, C-5),
119.6 (CH, C-4 Fu), 119.4 (CH, C-8), 113.8 (CH, C-4), 111.7 (CH,
3
CDCl3, 25 °C): δ = 9.61 (s, 1 H, NH), 8.50 (d, JH,H = 5.1 Hz, 1
H, 3-H), 8.14 (d, 3JH,H = 7.8 Hz, 1 H, 8-H), 7.96 (d, 3JH,H = 5.3 Hz,
3
3
1 H, 4-H), 7.66 (d, JH,H = 8.2 Hz, 1 H, 5-H), 7.61 (t, JH,H
=
5.8 Hz, 1 H, 7-H), 7.39 (d, 3JH,H = 3.5 Hz, 1 H, 6-H), 7.36 (d, 3JH,H
= 3.7 Hz, 1 H, 4-H Fu), 7.32 (t, 3JH,H = 6.8 Hz, 1 H, 3-H Fu), 4.01
(s, 3 H, OCH3) ppm. 13C NMR (100 MHz, CDCl3, 25 °C): δ =
159.2 (Cq., Fu-COO), 157.8 (Cq., C-2 Fu), 143.7 (Cq., C-5 Fu),
140.6 (Cq., C-8a), 139.0 (CH, C-3), 131.9 (Cq., C-9a), 131.6 (Cq.,
C-1), 130.6 (Cq., C-4a), 128.8 (CH, C-7), 121.5 (CH, C-5), 120.9
(Cq., C-4b), 120.3 (CH, C-6), 119.9 (CH, C-4 Fu), 114.8 (CH, C-
4), 111.9 (CH, C-8), 109.7 (CH, C-3 Fu), 52.1 (OCH3) ppm. IR
C-3 Fu), 51.97 (OCH ), 21.5 (CH Ts) ppm. IR (neat, ATR): ν =
˜
3
3
3104, 1718, 1520, 1378, 1296, 1173, 1141, 770 cm–1. FD-MS: m/z
(%) = 446.0 (100) [M]+. HR-MS: calcd. for C24H18N2NaO5S+ [M
+ Na]+ 469.0829; found 469.0822. C24H18N2O5S (446.0936): calcd.
C 64.56, H 4.06, N 6.27; found C 64.16, H 4.07, N 6.03.
1-[5-(tert-Butoxycarbonyl)furan-2-yl]-5-tosyl-5H-pyrido[4,3-b]-
indole-3-carboxylic Acid (10b): According to the procedure for 10a,
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Eur. J. Org. Chem. 2011, 2836–2844