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LETTER
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79, 1356. (b) Qadir, M.; Priestley, R. E.; Rising, T. W. D. F.;
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(15) General Procedure for the Intramolecular Buchwald
Arylation (0.1–0.4 mmol Scale)
A thick-glassed, screw-capped pressure tube (50 mL) was
charged with a suspension of the requisite 2-aminoethyl-
substituted imidazo[4,5-b]pyridine intermediate 17 (1.0
equiv) and Cs2CO3 (1.1 equiv) in toluene (3 mL/mmol),
along with a stir bar. Meanwhile, Pd(OAc)2 (0.05 equiv) and
BINAP (0.1 equiv) were weighed into a vial, suspended in
toluene (2–3 mL), and shaken while immersed in a 100 °C
oil bath for 2 min. The resulting clear, purple, or light-brown
catalyst solution was added in one portion to the vigorously
stirred reaction mixture. The tube was filled with argon,
capped and stirred at 100 °C for 16 h (48 h for 3). The
mixture was allowed to cool to ambient temperature, filtered
through a plug of Celite, and the latter was additionally
washed with EtOAc. The filtrate was concentrated under
reduced pressure, and the crude material was purified by
column chromatography on silica gel using a 0–5% gradient
of MeOH in CH2Cl2 to furnish target compounds 3 and 18a–m.
(16) Crystallographic data (excluding structure factors) for
compound 3 have been deposited with the Cambridge
Crystallographic Data Centre as supplementary publication
number CCDC 1004050. Copies of the data can be obtained
free of charge, on application to CCDC, 12 Union Road,
Cambridge CB2 1EZ, UK [fax: +44(1223)336033 or e-mail:
deposit@ccdc.cam.ac.uk].
(18) General Procedure for the Reductive Alkylation of 16
(0.5 mmol Scale)
Equimolar amounts of 16 and the requisite aldehyde were
combined in CH2Cl2 (5 mL). Anhydrous MgSO4 (500 mg)
was added, and the mixture was stirred at r.t. overnight. The
MgSO4 was filtered off, washed with CH2Cl2 (50 mL), and
the combined filtrate and washings were concentrated in
vacuo. The residue was dissolved in MeOH (5 mL), treated
with NaBH4 (0.3 mmol), and the mixture stirred at r.t. for 1
h, at which point the reaction was complete according to
TLC analysis. The mixture was partitioned between EtOAc
(50 mL) and sat. aq NaHCO3 (25 mL), the organic layer
separated, dried over anhydrous MgSO4, filtered, and
concentrated. The crude product was analyzed by 1H NMR
spectroscopy and used in the next step without further
purification.
(19) Characterization Data for Selected Compounds
Compound 18d: white solid; mp 131–133 °C. 1H NMR (500
MHz, CDCl3): δ = 8.71 (dd, J = 7.9, 1.45 Hz, 1 H), 8.34 (dd,
J = 4.75, 1.25 Hz, 1 H), 8.11 (dd, J = 7.95, 1.25 Hz, 1 H),
7.34–7.37 (m, 1 H), 7.26 (dd, J = 7.95, 4.75 Hz, 1 H), 7.21
(d, J = 8.55 Hz, 2 H), 7.06 (t, J = 7.85 Hz, 2 H), 6.87 (d, J =
8.6 Hz, 2 H), 4.58 (s, 2 H), 4.43–4.45 (m, 2 H), 3.80 (s, 3 H),
3.64–3.66 (m, 2 H). 13C NMR (125 MHz, CDCl3): δ = 159.3,
153.3, 149.8, 148.7, 143.4, 134.2, 132.1, 131.9, 129.3,
129.0, 126.4, 120.7, 119.1, 118.0, 117.9, 114.4, 56.9, 55.5,
51.7, 45.5. LC–MS (ESI): m/z = 357.40 [M + H]+. Anal.
Calcd for C22H20N4O: C, 74.14; H, 5.66; N, 15.72. Found: C,
73.98; H, 5.57; N, 15.84.
Compound 18g: white solid; mp 170–172 °C. 1H NMR (500
MHz, CDCl3): δ = 8.67 (dd, J = 8.05, 1.5 Hz, 1 H), 8.34 (dd,
J = 4.8, 1.25 Hz, 1 H), 8.11 (dd, J = 7.75, 1.4 Hz, 1 H), 7.26–
7.36 (m, 4 H), 7.21 (d, J = 8.3 Hz, 2 H), 7.07 (t, J = 7.9 Hz,
1 H), 6.98 (d, J = 8.3 Hz, 1 H), 4.60 (s, 2 H), 4.47–4.49 (m,
2 H), 3.65–3.67 (m, 2 H). 13C NMR (125 MHz, CDCl3): δ =
153.2, 149.2, 148.6, 143.6, 136.1, 134.3, 133.5, 132.1,
132.0, 129.2, 129.0, 126.6, 121.1, 119.2, 118.5, 118.1, 57.1,
52.5, 45.0. LC–MS (ESI): m/z = 361.31 [M + H]+. Anal.
Calcd for C21H17ClN4: C, 69.90; H, 4.75; N, 15.53. Found:
C, 70.02; H, 4.67; N, 15.64.
Compound 18k: beige solid, mp 134–136 °C. 1H NMR (500
MHz, CDCl3): δ = 7.83–7.99 (m, 2 H), 7.77 (dd, J = 8.2, 1.7
Hz, 1 H), 7.53 (d, J = 8.2 Hz, 1 H), 7.46 (d, J = 1.7 Hz, 1 H),
4.33–4.38 (m, 2 H), 3.85–3.33 (m, 2 H), 3.33–3.47 (m, 2 H),
2.83 (s, 3 H), 1.38–1.53 (m, 9 H), 1.12–1.28 (m, 3 H). 13
C
NMR (125 MHz, CDCl3): δ = 154.8, 149.6, 147.7, 143.1,
132.3, 130.1, 128.6, 128.5, 126.3, 119.2, 118.7, 114.3, 60.1,
53.4, 40.5, 40.4, 30.1, 27.1, 26.5, 22.8. LC–MS (ESI): m/z =
381.92 [M + H]+. Anal. Calcd for C22H25ClN4: C, 69.16; H,
6.86; N, 14.64. Found: C, 69.07; H, 6.79; N, 14.72.
(17) Krasavin, M. Tetrahedron Lett. 2012, 53, 2876.
(20) Trost, B. M. Angew. Chem., Int. Ed. Engl. 1995, 34, 259.
Synlett 2014, 25, 2323–2326
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