M. Alfonsi, A. Arcadi, G. Bianchi, F. Marinelli, A. Nardini
FULL PAPER
127.6, 142.1, 148.9, 211.3 ppm. MS (EI): m/z (%) = 214 (100)
[M]+, 171 (52), 144 (58). C13H14N2O (214.26): calcd. C 72.87, H
6.59, N 13.07; found C 72.90, H 6.73, N 13.08.
(200 MHz, CDCl3): δ = 2.11 (s, 3 H), 2.16 (s, 3 H), 2.81–3.06 (m,
6 H), 4.48 (t, J = 6.4 Hz, 2 H), 7.01 (dd, J = 7.8 and 4.6 Hz, 2 H),
7.06 (s, 1 H), 7.84 (d, J = 7.8 Hz, 1 H), 8.27 (d, J = 4.6 Hz, 1
H) ppm. 13C NMR (50.3 MHz, CDCl3): δ = 18.8, 29.9, 38.8, 43.3,
43.6, 111.9, 114.8, 120.0, 125.8, 126.7, 142.3, 147.0, 206.5,
207.9 ppm. MS (EI): m/z (%) = 258 (84) [M]+, 202 (100), 131 (66).
C15H18N2O2 (258.32): calcd. C 69.74, H 7.02, N 10.84; found C
69.73, H 7.01, N 10.84.
4-(1H-Pyrrolo[2,3-b]pyridin-1-yl)butan-2-one (4a): Eluent for
chromatography: n-hexane/ethyl acetate, 70:30 v/v. Yield: 0.068 g
1
(54%). IR (KBr): ν = 1720 cm–1. H NMR (200 MHz, CDCl ): δ
˜
3
= 2.07 (s, 3 H), 3.02 (t, J = 6.4 Hz, 2 H), 4.53 (t, J = 6.4 Hz, 2 H),
6.38 (d, J = 3.5 Hz, 1 H), 7.03 (dd, J = 7.8 and 4.8 Hz, 1 H), 7.26
(d, J = 3.5 Hz, 1 H), 7.86 (d, J = 7.8 Hz, 1 H), 8.27 (d, J = 4.8 Hz,
1 H) ppm. 13C NMR (50.3 MHz, CDCl3): δ = 30.2, 39.3, 43.4, 99.3,
115.7, 120.4, 128.8, 129.1, 141.3, 142.4, 206.7 ppm. MS (EI): m/z
(%) = 189 (100) [M + 1]+, 145 (72), 118 (45). C11H12N2O (188.22):
calcd. C 70.19, H 6.43, N 14.88; found C 70.24, H 6.49, N 14.75.
4-[1-(3-Oxobutyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]pentan-2-one (5c):
Eluent for chromatography: n-hexane/ethyl acetate, 50:50 v/v. Yield:
0.227 g (98 %). IR (neat): ν = 1720 cm–1 1H NMR (200 MHz,
.
˜
CDCl3): δ = 1.34 (d, J = 6.8 Hz, 3 H), 2.10 (s, 3 H), 2.12 (s, 3 H),
2.71–2.84 (m, 2 H), 3.03 (t, J = 6.4 Hz, 2 H), 3.40–3.70 (m, 1 H),
4.92 (t, J = 6.4 Hz, 2 H), 7.00–7.07 (m, 2 H), 7.90 (d, J = 7.9 Hz,
1 H), 8.28 (d, J = 4.7 Hz, 1 H) ppm. 13C NMR (50.3 MHz, CDCl3):
δ = 21.3, 26.8, 30.2, 30.6, 39.2, 43.6, 51.3, 115.1, 118.1, 120.8, 121.6,
124.8, 127.4, 142.6, 206.7, 208.1 ppm. MS (EI): m/z (%) = 273 (62)
[M + 1]+, 272 (16) [M]+, 216 (100). C16H20N2O2 (272.34): calcd. C
70.56, H 7.40, N 10.29; found C 70.55, H 7.43, N 10.34.
4-(4-Chloro-1H-pyrrolo[2,3-b]pyridin-1-yl)butan-2-one (4b): Eluent
for chromatography: n-hexane/ethyl acetate, 70:30 v/v. Yield:
0.091 g (48 %). IR (KBr): ν = 1720 cm–1 1H NMR (200 MHz,
.
˜
CDCl3): δ = 2.06 (s, 3 H), 3.10 (t, J = 6.7 Hz, 2 H), 4.54 (t, J =
6.7 Hz, 2 H), 6.56 (d, J = 3.2 Hz, 1 H), 7.15 (d, J = 5.1 Hz, 1 H),
7.59 (d, J = 3.2 Hz, 1 H), 8.19 (d, J = 5.1 Hz, 1 H) ppm. MS (EI):
m/z (%) = 223 (59) [M]+, 180 (100), 152 (44). C11H11ClN2O
(222.67): calcd. C 59.33, H 6.98, N 12.58; found C 59.27, H 6.92,
N 12.61.
4-[1-(3-Oxobutyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]octan-2-one (5d):
Eluent for chromatography: n-hexane/ethyl acetate, 50:50 v/v. Yield:
0.195 g (73 %). IR (neat): ν = 1720, 1710 cm–1 1H NMR
.
˜
(200 MHz, CDCl3): δ = 0.81 (t, J = 7.1 Hz, 3 H), 1.15–1.35 (m, 4
H), 1.68–1.99 (m, 1 H), 2.03 (s, 3 H), 2.10 (s, 3 H), 2.18–2.26 (m,
1 H), 2.47–2.81 (m, 2 H), 3.02 (t, J = 6.4 Hz, 2 H), 3.30–3.50 (m,
1 H), 4.49 (t, J = 6.4 Hz, 2 H), 6.99–7.06 (m, 2 H), 7.90 (d, J =
7.8 Hz, 1 H), 8.27 (d, J = 4.5 Hz, 1 H) ppm. 13C NMR (50.3 MHz,
CDCl3): δ = 13.9, 22.6, 29.7, 30.3, 30.5, 32.6, 35.6, 39.2, 43.5, 50.2,
115.1, 116.3, 119.7, 125.7, 127.6, 142.6, 147.4, 206.7, 208.2 ppm.
MS (EI): m/z (%) = 316 (100) [M + 2]+, 315 (16) [M + 1]+, 258
(25). C19H26N2O2 (314.42): calcd. C 72.58, H 8.33, N 8.91; found
C 72.59, H 8.37, N 8.82.
4-(1H-Pyrrolo[2,3-b]pyridin-1-yl)octan-2-one (4c): Eluent for
chromatography: n-hexane/ethyl acetate, 70:30 v/v. Yield: 0.170 g
(82 %). IR (KBr): ν = 1720, 890 cm–1 1H NMR (200 MHz,
.
˜
CDCl3): δ = 0.78 (t, J = 7.2 Hz, 3 H), 0.89–1.30 (m, 4 H), 1.88–
1.93 (m, 2 H), 2.03 (s, 3 H), 2.95–3.32 (m, 2 H), 4.95–5.10 (m, 1
H), 6.43 (d, J = 3.5 Hz, 1 H), 7.03 (dd, J = 7.8 and 4.7 Hz, 1 H),
7.22 (d, J = 3.5 Hz, 1 H), 7.86 (d, J = 7.8 Hz, 1 H), 8.29 (d, J =
4.7 Hz, 1 H) ppm. 13C NMR (50.3 MHz, CDCl3): δ = 13.8, 22.2,
28.3, 30.2, 34.4, 48.8, 52.1, 99.7, 115.7, 120.9, 126.6, 128.7, 142.5,
206.5 ppm. MS (EI): m/z (%) = 245 (100) [M + 1]+, 145 (25), 119
(9). C15H20N2O (244.33): calcd. C 73.74, H 8.25, N 11.47; found C
73.81, H 8.40, N 11.35.
4-{3-[3-Oxo-1-thiophen-2-yl-3-(p-tolyl)propyl]-1H-pyrrolo[2,3-b]-
pyridin-1-yl}butan-2-one-5e: Eluent for chromatography: n-hexane/
ethyl acetate, 50:50 v/v. Yield: 0.141 g (40 %). IR (neat): ν =
˜
1720 cm–1. 1H NMR (200 MHz, CDCl3): δ = 2.11 (s, 3 H), 2.39 (s,
3 H), 2.98–3.09 (m, 2 H), 3.75 (d, J = 7.0 Hz, 2 H), 4.46–4.58 (m,
3 H), 6.88 (s, 1 H), 6.99–7.29 (m, 6 H), 7.81–7.91 (m, 3 H), 8.25–
8.31 (m, 1 H) ppm. 13C NMR (50.3 MHz, CDCl3): δ = 21.6, 30.2,
33.4, 39.3, 43.5, 45.7, 99.3, 115.4, 115.7, 123.6, 124.2, 125.9, 126.6,
127.8, 128.2, 128.8, 129.1, 129.3, 142.6, 142.8, 144.0, 197.3,
206.6 ppm. MS (EI): m/z (%) = 416 (39) [M]+, 298 (67), 284 (100).
C25H24N2O2S (416.54): calcd. C 72.09, H 5.81, N 6.73; found C
72.05, H 5.69, N 6.66.
Typical Experimental Procedure for the Michael Addition of N-1-
Substituted 7-Azaindoles 4 to α,β-Enone 2: α,β-Enone 2 (2.52 mmol)
and Na[AuCl4]·2H2O (0.042 mmol) were added to a screw-top vial
(60×18 mm) with a solid-top cap charged with a solution of N-1-
substituted 7-azaindoles 4 (0.850 mmol) in absolute ethanol
(2 mL). The resulting mixture was heated whilst stirring at 140 or
100 °C (for more reactive enones). The reaction was monitored by
TLC and GC–MS. After cooling, the mixture was filtered to re-
move the catalyst and the solvent concentrated under reduced pres-
sure. The residue was directly purified by flash chromatography
(silica gel, n-hexane/ethyl acetate) to give product 5.
4-[1-(3-Oxobutyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-4-phenylbutan-2-
one (5f): Eluent for chromatography: n-hexane/ethyl acetate, 50:50
v/v. Yield: 0.128 g (45 %). IR (neat): ν = 1720 cm–1 1H NMR
.
4-{1-[1-(2-Oxopropyl)pentyl]-1H-pyrrolo[2,3-b]pyridin-3-yl}octan-2-
one (5a): Eluent for chromatography: n-hexane/ethyl acetate, 60:40
˜
(200 MHz, CDCl3): δ = 2.08 (s, 6 H), 3.01 (t, J = 6.4 Hz, 2 H),
3.14–3.22 (m, 2 H), 4.49 (t, J = 6.4 Hz, 2 H), 4.65–4.85 (m, 1 H),
6.90 (dd, J = 7.8 and 4.7 Hz, 1 H), 7.11–7.26 (m, 6 H), 7.61 (d, J =
7.8 Hz, 1 H), 8.23 (d, J = 4.7 Hz, 1 H) ppm. 13C NMR (50.3 MHz,
CDCl3): δ = 30.2, 30.6, 38.1, 39.3, 43.5, 49.8, 115.3, 115.9, 125.6,
126.5, 127.6, 127.7, 127.9, 128.5, 142.8, 143.7, 206.7, 206.9 ppm.
MS (EI): m/z (%) = 336 (100) [M + 2]+, 278 (18). C21H22N2O2
(334.41): calcd. C 75.42, H 6.63, N 8.38; found C 75.48, H 6.41, N
8.33.
v/v. Yield: 0.050 g (16 %). IR (neat): ν = 1730 cm–1 1H NMR
.
˜
(200 MHz, CDCl3): δ = 0.77 (s, 3 H), 0.81 (s, 3 H), 1.10–1.85 (m,
10 H), 1.93 (s, 3 H), 2.03 (s, 3 H), 2.04–2.23 (m, 2 H), 3.02–3.07
(m, 2 H), 3.14–3.21 (m, 2 H), 3.25–342 (m, 1 H), 5.10–5.13 (m, 1
H), 6.99 (s, 1 H), 7.03 (d, J = 4.3 Hz, 1 H), 7.86 (d, J = 7.8 Hz, 1
H), 8.27 (d, J = 4.3 Hz, 1 H) ppm. 13C NMR (50.3 MHz, CDCl3):
δ = 13.8, 13.9, 22.2, 22.5, 22.7, 27.4, 29.7, 30.1, 32.9, 34.2, 35.5,
50.3, 51.8, 51.9, 115.2, 119.2, 123.2, 123.4, 127.5, 128.7, 142.5,
206.3, 208.1 ppm. MS (EI): m/z (%) = 371 (100) [M + 1]+, 313 (98).
C23H34N2O2 (370.53): calcd. C 74.55, H 9.25, N 7.56; found C
74.43, H 9.20, N 7.48.
4-(1-Benzyl-1H-pyrrolo[2,3-b]pyridin-3-yl)octan-2-one (5g): Eluent
for chromatography: n-hexane/ethyl acetate, 50:50 v/v. Yield:
0.145 g (51 %). IR (neat): ν = 1720 cm–1 1H NMR (200 MHz,
.
˜
4-[3-(3-Oxobutyl)-1H-pyrrolo[2,3-b]pyridin-1-yl]butan-2-one (5b): CDCl3): δ = 0.80 (t, J = 6.9 Hz, 3 H), 1.14–1.29 (m, 4 H), 1.62–
Eluent for chromatography: n-hexane/ethyl acetate, 50:50 v/v. Yield: 1.73 (m, 2 H), 1.97 (s, 3 H), 2.75–2.80 (m, 2 H), 3.37–3.43 (m, 1
0.096 g (44 %). IR (KBr): ν = 1730, 1710 cm–1 1H NMR H), 5.45 (s, 2 H), 6.95 (s, 1 H), 7.04 (dd, J = 7.8 and 4.7 Hz, 1 H),
.
˜
2400
www.eurjoc.org
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2006, 2393–2402