Synthesis of 2-(piperidin-1-yl)aniline (6b). It was synthesized in a procedure similar to the one described for 3b except
that 1-(2-nitrophenyl)piperidine (4.31 g, 21 mmol) was used instead of 1-(2-nitrophenyl)pyrrolidine. Yield: 3.65 g (99%).
1H-NMR (400 MHz, CDCl3): 7.00 (d, J = 8.0 Hz, 1H), 6.92 (t, J = 7.5 Hz, 1H), 6.75 (t, J = 7.1 Hz, 2H), 3.98 (s, 2H), 2.84
(s, 4H), 1.71 (quint., J = 5.3 Hz, 4H), 1.58 (s, 2H). 13C-NMR (101 MHz, CDCl3): 141.7, 140.9, 124.3, 119.9, 118.6, 115.1,
52.8, 27.0, 24.5. HRMS (ESI) for ([M+H]+: C11H17N2 ), calculated: 177.1392, found: 177.1395.
+
Synthesis of 1-(2-bromophenyl)pyrrolidine (3c). 1,4-Dibromobutane (1 equiv., 17.4 mmol, 2.1 mL) and N,N-
diisopropylethylamine (2.4 equiv., 41.9 mmol, 7.3 mL) were added to a solution of 2-bromoaniline (1 equiv., 17.4 mmol,
3.01 g) in toluene (20 mL). The reaction was heated at 100°C for 96 h. The product was then purified by column
1
chromatography (on SiO2, Hexane) to afford the pure compound 3c as yellow oil. Yield: 2.86 g (72%). H-NMR (400
MHz, CDCl3): 7.51 (d, J = 7.9 Hz, 1H), 7.20 (t, J = 7.4 Hz, 1H), 6.93 (d, J = 8.1 Hz, 1H), 6.74 (t, J = 7.5 Hz, 1H), 3.36 (t, J
= 6.2 Hz, 4H), 1.95 (t, J = 6.3 Hz, 4H). 13C-NMR (101 MHz, CDCl3): 148.9, 134.7, 127.9, 121.4, 118.0, 114.0, 51.4, 25.2.
HRMS (ESI) for ([M+H]+: C10H13BrN +), calculated: 226.0231, found: 226.0233.
Synthesis of N1-(2-(azetidin-1-yl)phenyl)-N2,N2-dimethylbenzene-1,2-diamine (4H). A 100 mL reaction vessel was
charged with Pd2(dba)3 (0.02 equiv., 0.27 mmol, 0.25 g), bis(diphenylphosphino)-ferrocene (dppf) (0.04 equiv., 0.54
mmol, 0.30 g), NaOt-Bu (1.3 equiv., 17.6 mmol, 1.69 g) and toluene (50 mL) under a N2 atmosphere. 2-Bromo-N,N-
dimethylaniline (1.1 equiv., 14.9 mmol, 2.98 g) and 2-(azetidin-1-yl)aniline 4b (13.5 mmol, 2.0 g) were added to the
reaction mixture. The resulting brown solution was vigorously stirred for 16 h at 110 °C. The solution was then cooled to
room temperature and filtered through Celite. Removal of the solvent yielded a black liquid which was then dissolved in
dichloromethane and filtered through silica. The solvent was evaporated and the crude product was purified by column
chromatography (on SiO2, Hexane/Ethyl Acetate 9:1) to afford the pure compound 4H as a brown oil. Yield: 2.54 g
(84%). 1H-NMR (400 MHz, CDCl3): 7.30-7.21 (m, 1H), 7.13 (d, J = 7.7 Hz, 1H), 7.05 (t, J = 7.6 Hz, 1H), 6.98 (quint., J =
9.1, 8.4 Hz, 2H), 6.82 (dt, J = 22.8, 7.4 Hz, 2H), 6.66 (d, J = 7.9 Hz, 1H), 6.26 (s, 1H), 3.85 (t, J = 7.1 Hz, 4H), 2.73 (s,
6H), 2.31-2.14 (m, 2H). 13C-NMR (101 MHz, CDCl3): 146.2, 141.1, 140.3, 130.4, 124.5, 123.7, 123.6, 119.6, 119.5,
118.3, 114.1, 112.7, 53.9, 44.3, 17.6. HRMS (ESI) for ([M+H]+: C17H22N3 ), calculated: 268.1814, found: 268.1812.
+
Synthesis of bis(2-(pyrrolidin-1-yl)phenyl)amine (3H). It was synthesized in a procedure similar to the one described
for 4H except that 1-(2-bromophenyl)pyrrolidine 3c (1 equiv., 27 mmol, 6.24 g) was used instead of 2-bromo-N,N-
dimethylaniline and 2-(pyrrolidin-1-yl)aniline 3b (1.2 equiv., 32.4 mmol, 5.26 g) was used instead of 2-(azetidin-1-
yl)aniline. Yield: 6.81 g (82%). 1H-NMR (400 MHz, CDCl3): 7.22 (d, J = 7.9 Hz, 2H), 7.05 (d, J = 7.6 Hz, 2H), 6.93 (t, J =
7.3 Hz, 2H), 6.87 (t, J = 7.5 Hz, 2H), 6.68 (s, 1H), 3.09 (t, J = 6.0 Hz, 8H), 1.90 (quint., J = 3.2 Hz, 8H). 13C-NMR (101
MHz, CDCl3): 140.8, 137.3, 122.6, 120.6, 118.4, 117.3, 51.3, 24.7. HRMS (ESI) for ([M+H]+: C20H26N3 ), calculated:
+
308.2127, found: 308.2124.
Synthesis of N1,N1-dimethyl-N2-(2-morpholinophenyl)benzene-1,2-diamine (5H). It was synthesized in a procedure
similar to the one described for 4H except that 2-morpholinoaniline 5b (2.75 g, 15.4 mmol) was used instead of 2-
(azetidin-1-yl)aniline. Yield: 3.67 g (80%). 1H-NMR (400 MHz, CDCl3): 7.63 (s, 1H), 7.52-7.37 (m, 2H), 7.17-6.97 (m, 4H),
6.96-6.82 (m, 2H), 3.96-3.77 (m, 4H), 3.06-2.91 (m, 4H), 2.72 (s, 6H). 13C-NMR (101 MHz, CDCl3): 142.9, 141.4, 137.7,
137.6, 124.6, 124.1, 120.1, 120.0, 119.9, 119.8, 115.6, 114.2, 67.9, 52.0, 44.3. HRMS (ESI) for ([M+H]+: C18H23N3O +),
calculated: 298.1919, found: 298.1921.
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