Beilstein J. Org. Chem. 2012, 8, 1037–1047.
ture and diluted with diethyl ether. The organic phase was 2.25 mmol, 1.3 equiv) was added dropwise and the mixture was
washed with sat. aq NaCl, and the aqueous phase was extracted stirred for 1 h. Compound 19 (0.38 g, 2.27 mmol, 1.3 equiv) in
two times with diethyl ether. The combined organic extracts THF (2 mL) was added dropwise at −80 °C and the reaction
were then dried over MgSO4 and filtered, and the solvent was mixture was stirred for another 1 h, after which it was quenched
removed. The raw product was preadsorbed onto aluminium with trimethylborate (0.23 g, 2.24 mmol, 1.3 equiv). The mix-
oxide, activity III. Column chromatography (Al2O3, activity III, ture was allowed to warm to 0 °C and was stirred for 0.5 h. At
dichloromethane/ethyl acetate/hexane 1:1:2
→
room temperature 10 (0.49 g, 1.70 mmol), Pd(PPh3)2Cl2
dichloromethane/ethyl acetate 1:1, Rf (Al2O3, dichloromethane/ (0.07 g, 0.1 mmol, 6 mol %) and THF (4 mL) were added. The
ethyl acetate/hexane 1:1:2) = 0.27) gave 2 as a pale yellow solid reaction mixture was heated under reflux, and aq K2CO3
(1.0 g, 4.1 mmol, 41%). Recrystallization from methanol gave (2.8 mL, 1 M, 2.8 mmol, 1.65 equiv) was added meanwhile. It
brown crystals of 2, which retained one solvent molecule as was kept under reflux for 70 h, then cooled to room tempera-
indicated by X-ray and elemental analysis. Mp 119 °C (release ture and diluted with diethyl ether. The organic phase was
of methanol), 137 °C (melting of the remaining solid); 1H NMR washed with sat. aq NaCl and the aqueous phase was extracted
(600 MHz, CDCl3) δ 12.12 (s, 1H, N-H), 8.98 (dd, 3JH,H = two times with diethyl ether. The combined organic extracts
4.4 Hz, 4JH,H = 1.7 Hz, 1H, 1-H), 8.22 (dd, 3JH,H= 8.1 Hz, were then dried over MgSO4 and filtered, and the solvent was
4JH,H = 1.6 Hz, 1H, 3-H), 8.10 (d, 3JH,H = 8.5 Hz, 1H, 8-H), removed. Column chromatography (SiO2, diethyl ether, Rf =
7.88 (d, 3JH,H= 8.5 Hz, 1H, 9-H), 7.71 (d, 3JH,H= 8.7 Hz, 1H, 0.55) gave 6 as a colorless solid (0.55 g, 1.47 mmol, 85%). mp
6-H), 7.64 (d, 3JH,H= 8.8 Hz, 1H, 5-H), 7.56 (dd, 3JH,H= 125–126 °C; 1H NMR (600 MHz, CDCl3) δ 8.32 (dd, 3JH,H=
8.0 Hz, 3JH,H = 4.4 Hz, 1H, 2-H), 7.04 (dt, 3JH,H= 2.6 Hz, 7.9 Hz, 4JH,H = 1.1 Hz, 1H, 11-H), 7.85 (dd, 3JH,H = 7.9 Hz,
4JH,H = 1.4 Hz, 1H, 14-H), 6.90 (ddd, 3JH,H = 3.7 Hz, J = 3JH,H = 7.8 Hz, 1H, 10-H), 7.83 (ddd, 3JH,H= 7.4 Hz, 4JH,H =
2.4 Hz, 4JH,H = 1.4 Hz, 1H, 15-H), 6.32 (pseudo-dt, 3JH,H= 1.6 Hz, 5JH,H = 0.7 Hz, 1H, 19-H), 7.46 (dd, 3JH,H= 7.8 Hz,
3.6 Hz, J = 2.5 Hz, 1H, 16-H) ppm; 13C NMR (151 MHz, 4JH,H = 1.0 Hz, 1H, 9-H), 7.43–7.41 (m, 1H, 16-H), 7.39 (dd,
CDCl3) δ 150.9 (s, C-10), 148.8 (d, C-1), 145.5 (s, C-11), 145.2 3JH,H= 3.3 Hz, 4JH,H = 1.8 Hz, 1H, 4-H), 7.33 (ddd, 3JH,H =
(s, C-12), 136.6 (d, C-3), 136.2 (d, C-8), 132.3 (s, C-13), 129.1 7.5 Hz, 3JH,H = 7.1 Hz, 4JH,H = 1.4 Hz, 1H, 17-H), 7.30 (ddd,
(s, C-4), 126.8 (d, C-6), 126.4 (s, C-7), 124.4 (d, C-5), 122.8 (d, 3JH,H = 7.4 Hz, 3JH,H = 7.1 Hz, 4JH,H = 1.3 Hz), 6.50 (dd, 3JH,H
C-2), 122.0 (d, C-14), 119.1 (d, C-9), 109.8 (d, C-16), 109.2 (d, = 3.3 Hz, 4JH,H = 1.7 Hz, 1H, 6-H), 6.28 (dd, 3JH,H = 3.3 Hz,
C-15) ppm; EIMS (70 eV) m/z (% relative intensity): [M]+● 3JH,H = 3.3 Hz, 1H, 5-H), 4.25 (s, 3H, 14-H), 1.33 (s, 9H, 1-H)
247/246/245/244/243 (2/16/100/12/4); UV–vis (CH2Cl2) λmax, ppm; 13C NMR (151 MHz, CDCl3) δ 151.6 (s, C-8), 150.1 (s,
nm (log εmax): 339 (4.24), 311 (4.31), 235 (3.46); UV–vis C-13), 149.7 (s, C-12), 149.3 (s, C-3), 142.5 (s, C-20), 137.2 (s,
(CH3OH) λmax, nm (log εmax): 345 (4.13), 312 (4.24), 237 C-15), 136.8 (d, C-10), 134.0 (s, C-7), 123.9 (d, C-4), 123.2 (d,
(4.32) IR (ATR) :3610 (w), 3185 (m), 3113 (m), 2927 (w), C-17), 123.1 (d, C-9), 122.6 (d, C-11), 122.5 (d, C-18), 120.0
2820 (w), 1617 (w), 1585 (m), 1554 (m), 1503 (m), 1459 (m), (d, C-19), 116.0 (d, C-6), 110.6 (d, C-5), 109.9 (d, C-16), 83.9
1423 (m), 1408 (m), 1378 (m), 1338 (w), 1262 (w), 1215 (w), (s, C-2), 32.8 (q, C-14), 27.5 (q, C-1) ppm; EIMS (70 eV) m/z
1145 (m), 1125 (s), 1080 (w), 1030 (s), 936 (w), 882 (w), 839 (% relative intensity): [M]+● 375/374 (2/6), [M – Boc +
(s), 779 (s), 728 (s), 679 (s), 626 (m), 606 (s), 569 (m) cm−1; methyl]+● 290/289/288/287/286 (10/65/100/67/93), [M −
anal. calcd. for C16H11N3·CH3OH: C 73.63, H 5.45, N 15.15; Boc]+● 275/274/273 (6/32/35), [M − Boc-pyrrole + H+]+● 209/
found: C 73.30, H 5.33, N 15.25.
208/207/206 (3/18/16/12), [N-methylbenzimidazole]+● 132/
131/130/129 (4/39/2/5); anal. calcd for C22 H22 N4 O2: C 70.57,
H 5.92, N 14.96; found: C 70.39, H 5.97,N 15.02.
Synthesis of 2-(N-methylbenz[d,e]imidazo-2-yl)-6-
(1-tert-butoxycarbonylpyrrol-2-yl)-pyridine (6)
Synthesis of 2-(N-methylbenz[d,e]imidazo-2-yl)-6-
(pyrrol-2-yl)-pyridine (3)
Diisopropylamine (0.22 g, 2.17 mmol, 1.3 equiv) was dissolved Compound 6 (0.43 g, 1.15 mmol) was dissolved in methanol
in THF (3 mL) and cooled to −80 °C. Whilst the temperature (35 mL). Sodium methanolate (0.13 g, 2.35 mmol, 2.0 equiv)
was kept constant, n-butyllithium (0.9 mL, 2.5 M in hexane, was added and the solution was stirred for 17 h under reflux.
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