The Journal of Organic Chemistry
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(t, J = 7.7 Hz, 1 H), 7.35−7.26 (m, 1 H), 6.83 (s, 1 H), 6.78 (s, 2 H),
5.92 (s, 2 H), 4.76 (s, 2 H); 13C NMR (100 MHz, CDCl3) δ 162.7,
154.6, 149.5, 147.9, 146.8, 136.7, 132.6, 124.9, 121.5, 121.5, 108.9,
108.9, 108.4, 101.1, 101.1, 101.0, 64.8; HRMS (EI) calcd for
C14H12N2O2 241.0972, found 241.0978.
(400 MHz, CDCl3) δ 8.40 (s, 1 H), 7.87 (d, J = 2.8 Hz, 1 H), 7.35
(d, J = 3.1 Hz, 1 H), 1.28 (s, 9 H); 13C NMR (100 MHz, CDCl3) δ
149.9, 143.9, 123.8, 121.2, 58.5, 29.6; HRMS (EI) calcd for C8H12N2S
169.0794, found 169.0795.
(E)-4-Methoxy-N-(pyridin-2-ylmethylene)aniline (76).32 This com-
pound was obtained as a yellow oil (441.2 mg, 89%): 1H NMR
(400 MHz, CDCl3) δ 8.70 (d, J = 5.0 Hz, 1 H), 8.63 (s, 1 H), 8.19
(d, J = 7.8 Hz, 1 H), 7.80 (td, J = 7.8, 1.8 Hz, 1 H), 7.34 (d, J = 8.7 Hz,
3 H), 6.95 (d, J = 8.8 Hz, 2 H), 3.84 (s, 3 H).
N-(Pyridin-2-ylmethylene)-2-(thiophen-2-yl)ethanamine (60).
1
This compound was obtained as a yellow oil (409.3 mg, 87%): H
NMR (300 MHz, CDCl3) δ 8.64 (ddd, J = 4.8, 1.6, 0.9 Hz, 1 H), 8.33
(s, 1 H), 8.00 (d, J = 7.9 Hz, 1 H), 7.75 (td, J = 7.8, 1.7 Hz, 1 H), 7.32
(ddd, J = 7.4, 4.8, 1.2 Hz, 1 H), 7.13 (dd, J = 5.1, 1.2 Hz, 1 H), 6.92
(dd, J = 5.1, 3.4 Hz, 1 H), 6.85 (dd, J = 3.4, 0.9 Hz, 1 H), 3.95 (td, J =
7.1, 1.3 Hz, 2 H), 3.27 (t, J = 7.1 Hz, 2 H); 13C NMR (100 MHz,
CDCl3) δ 162.9, 154.6, 149.6, 142.3, 136.8, 131.7, 126.9, 125.4, 125.0,
123.9, 121.6, 62.8, 31.5; HRMS (EI) calcd for C12H12N2S 217.0794,
found 217.0797.
General Procedure for Preparation of the N-Methyl-N-
phenylpyrido[1,2-a]indol-10-amines. To a dry 4-dram vial equip-
ped with a magnetic stir bar and screw cap, CsF (228 mg., 1.5 mmol,
6 equiv) was added under an inert atmosphere of nitrogen. Then, the
corresponding imine (0.25 mmol), THF (5 mL), and the aryne
precursor (0.75 mmol, 3 equiv) were added, and the vial was tightly
sealed. The reaction mixture was vigorously stirred at 100 °C for 16 h.
After cooling, the reaction mixture was diluted with ethyl acetate,
filtered, and concentrated under reduced pressure. The crude reaction
mixture was then purified by column chromatography using hexanes
or ethyl acetate/hexane mixtures with the addition of 1% triethylamine
as the eluent to afford pure product.
N-(tert-Butyl)-N-phenylpyrido[1,2-a]indol-10-amine (48). This
compound was obtained a yellow oil (56.1 mg, 72%): 1H NMR
(300 MHz, CDCl3) δ 8.23 (d, J = 7.1 Hz, 1 H), 7.83 (dd, J = 10.4, 8.2
Hz, 2 H), 7.48 (dt, J = 9.4, 1.2 Hz, 1 H), 7.40−7.34 (m, 1 H), 7.26
(ddd, J = 8.1, 7.0, 1.2 Hz, 2 H), 6.80 (ddd, J = 9.4, 6.3, 1.0 Hz, 1 H),
6.38 (ddd, J = 7.4, 6.4, 1.2 Hz, 1 H), 1.26 (s, 9 H); 13C NMR (100
MHz, CDCl3) δ 149.5, 134.5, 128.7, 128.3, 127.9, 124.3, 123.1, 122.4,
119.9, 119.4, 119.0, 117.6, 117.8, 112.6, 110.4, 107.9, 57.6, 30.4;
HRMS (EI) calcd for C22H22N2 314.1625, found 314.1633.
(E)-1-[3-(Pyridin-2-ylmethyleneamino)propyl]pyrrolidin-2-one
(62). This compound was obtained as a yellow oil (226.5 mg, 41%):
1H NMR (300 MHz, CDCl3) δ 8.60 (d, J = 3.8 Hz, 1 H), 8.34
(s, 1 H), 7.90 (d, J = 7.9 Hz, 1 H), 7.70 (ddt, J = 9.4, 7.7, 1.8 Hz, 1 H),
7.32−7.22 (m, 1H), 3.64 (t, J = 6.9 Hz, 2 H), 3.36 (q, J = 6.8 Hz, 4 H),
2.31 (t, J = 8.1 Hz, 2 H), 2.02−1.86 (m, 4 H); 13C NMR (75 MHz,
CDCl3) δ 175.1, 162.5, 154.4, 149.6, 136.7, 124.9, 121.6, 59.0, 47.3,
40.8, 31.2, 28.5, 18.0; HRMS (EI) calcd for C13H18N3O 232.1444,
found 232.1447.
(N1E,N2E)-N1,N2-Bis(pyridin-2-ylmethylene)ethane-1,2-diamine
(64). This compound was obtained as a yellow solid (298.9 mg, 54%):
1
mp 61−63 °C; H NMR (400 MHz, CDCl3) δ 8.61 (d, J = 4.1 Hz,
2 H), 8.40 (s, 2 H), 7.96 (d, J = 7.9 Hz, 2 H), 7.71 (td, J = 7.7, 1.8 Hz,
2 H), 7.28 (ddd, J = 7.5, 4.9, 1.3 Hz, 2 H), 4.05 (s, 4 H); 13C NMR
(100 MHz, CDCl3) δ 163.6, 154.5, 149.6, 136.7, 124.9, 121.5, 61.5;
HRMS (EI) calcd for C14H15N4 239.1291, found 239.1297.
tert-Butyl-(5-bromopyridin-2-ylmethylene)amine (66). This com-
pound was obtained as a brown solid (545.2 mg, 97%): mp 35−37 °C;
1H NMR (400 MHz, CDCl3) δ 8.68 (d, J = 1.6 Hz, 1 H), 8.29 (s,
1 H), 7.93 (d, J = 8.4 Hz, 1 H), 7.84 (dd, J = 8.5, 1.8 Hz, 1 H), 1.30 (s,
9 H); 13C NMR (100 MHz, CDCl3) δ 155.5, 154.2, 150.5, 139.4,
122.3, 121.9, 58.3, 29.7; HRMS (EI) calcd for C10H13BrN2 241.0335,
found 241.0336.
N-(Isopropyl)-N-phenylpyrido[1,2-a]indol-10-amine (50). This
compound was obtained as a yellow solid (49.9 mg, 66%): mp
1
129−132 °C; H NMR (400 MHz, CDCl3) δ 8.36 (d, J = 7.0 Hz,
1 H), 7.94 (d, J = 7.3 Hz, 1 H), 7.60 (d, J = 7.9 Hz, 1 H), 7.35−7.29
(m, 1 H), 7.11 (t, J = 7.8 Hz, 1 H), 6.88−6.82 (m, 1 H), 6.64 (dd, J =
18.4, 7.8 Hz, 1 H), 6.50 (t, J = 6.6 Hz, 1 H), 4.63−4.46 (m, 1 H), 1.25
(d, J = 6.5 Hz, 2 H); 13C NMR (100 MHz, CDCl3) δ 149.8, 134.8,
129.2, 128.4, 128.3, 124.4, 123.0, 122.4, 120.0, 119.5, 117.8, 116.4,
113.2, 110.4, 108.1, 107.0, 49.7, 21.5; HRMS (EI) calcd for C21H20N2
301.1699, found 301.1699.
tert-Butyl-(5-fluoropyridin-2-ylmethylene)amine (68). This com-
1
pound was obtained as a yellow oil (193.8 mg, 46%): H NMR (300
N-Cyclohexyl-N-phenylpyrido[1,2-a]indol-10-amine (52). This
MHz, CDCl3) δ 8.45 (d, J = 2.8 Hz, 1 H), 8.32 (s, 1 H), 8.05 (dd, J =
1
8.8, 4.8 Hz, 1 H), 7.43 (td, J = 8.2, 2.6 Hz, 1 H), 1.29 (s, 9 H); 13C
compound was obtained as a yellow oil (61.1 mg, 75%): H NMR
NMR (100 MHz, CDCl3) δ 160.2 (1JCF 257 Hz), 155.2, 152.1 (3JCF
4
(400 MHz, CDCl3) δ 8.36 (d, J = 7.0 Hz, 1 H), 7.94 (d, J = 7.1 Hz,
1 H), 7.62 (d, J = 8.1 Hz, 1 H), 7.32 (d, J = 7.6 Hz, 3 H), 7.11 (t, J =
7.9 Hz, 2 H), 6.88−6.81 (m, 1 H), 6.65 (t, J = 7.1 Hz, 1 H), 6.60
(d, J = 8.2 Hz, 2 H), 6.50 (t, J = 6.6 Hz, 1 H), 4.08 (t, J = 11.4 Hz, 1 H),
2.21 (d, J = 12.1 Hz, 2 H), 1.76 (d, J = 13.3 Hz, 2 H), 1.58 (d, J = 16.9
Hz, 1 H), 1.44 (q, J = 13.2 Hz, 2 H), 1.34−1.07 (m, 3 H), 0.98−0.87 (m,
1 H); 13C NMR (100 MHz, CDCl3) δ 149.8, 134.6, 129.2, 128.3, 128.2,
124.3, 123.0, 122.4, 120.0, 119.6, 117.9, 116.3, 113.1, 110.4, 108.1, 107.7,
58.5, 32.0, 26.3, 25.8; HRMS (EI) calcd for C24H24N2 341.2012, found
341.2013.
Hz), 137.5 (2JCF 24 Hz), 123.6 (2JCF 19 Hz), 122.3 (3JCF 4 Hz), 58.0,
29.8; HRMS (EI) calcd for C10H13FN2 181.1136, found 181.1137.
tert-Butyl-(6-bromopyridin-2-ylmethylene)amine (70). This com-
pound was obtained as colorless crystals (515.2 mg, 91%): mp 50−52
°C; 1H NMR (300 MHz, CDCl3) δ 8.27 (s, 1 H), 8.00 (dd, J = 7.6, 0.9
Hz, 1 H), 7.57 (t, J = 7.5 Hz, 1 H), 7.46 (dd, J = 7.8, 0.9 Hz, 1 H), 1.27
(s, 9 H); 13C NMR (100 MHz, CDCl3) δ 156.9, 155.4, 141.4, 139.0,
128.9, 119.5, 58.4, 29.7; HRMS (EI) calcd for C10H13BrN2 241.0355,
found 241.0339.
N-Adamantyl-N-phenylpyrido[1,2-a]indol-10-amine (54). This
tert-Butyl[6-(4-methoxyphenyl)pyridin-2-ylmethylene]amine
(71). This compound was obtained as a cream colored solid
compound was obtained as a yellow solid (61.2 mg, 62%): mp
1
1
(305.2 mg, 97%): mp 81−83 °C; H NMR (400 MHz, CDCl3) δ
128−130 °C; H NMR (400 MHz, CDCl3) δ 8.28 (d, J = 7.0 Hz,
8.45 (s, 1 H), 8.06−7.92 (m, 3 H), 7.73 (t, J = 7.7 Hz, 1 H), 7.64 (d,
J = 7.8 Hz, 1 H), 7.00 (d, J = 8.6 Hz, 2 H), 3.85 (s, 3 H), 1.35 (d, J =
2.5 Hz, 9 H); 13C NMR (100 MHz, CDCl3) δ 160.6, 157.4, 156.7,
155.5, 137.2, 131.9, 128.3, 120.6, 118.3, 114.3, 57.9, 55.5, 29.8; HRMS
(EI) calcd for C17H21N2O 269.1648, found 269.1653.
1 H), 7.86 (dd, J = 13.5, 8.2 Hz, 2 H), 7.49 (d, J = 9.4 Hz, 1 H), 7.38
(t, J = 7.1 Hz, 1 H), 7.32−7.23 (m, 2 H), 7.16−7.00 (m, 4 H), 6.85
(dd, J = 8.4, 6.3 Hz, 1 H), 6.74 (t, J = 6.9 Hz, 1 H), 6.44 (t, J = 6.2 Hz,
1 H), 2.19 (s, 6 H), 2.09 (s, 3 H), 1.65 (s, 6 H); 13C NMR (100 MHz,
CDCl3) δ 149.3, 135.1, 129.5, 128.2, 127.9, 124.2, 123.0, 122.3, 119.7,
119.2, 118.1, 112.2, 110.3, 107.9, 58.1, 42.5, 36.7, 30.5. HRMS (EI)
calcd for C28H28N2 393.2325, found 393.2324.
tert-Butyl(quinolin-2-ylmethylene)amine (72). This compound
1
was obtained as a yellow solid (417.8 mg, 84%): mp 54−56 °C; H
NMR (400 MHz, CDCl3) δ 8.53 (s, 1 H), 8.20 (q, J = 8.7 Hz, 2 H),
8.12 (d, J = 8.4 Hz, 1 H), 7.84 (d, J = 8.1 Hz, 1 H), 7.73 (t, J = 7.7 Hz,
1 H), 7.56 (t, J = 7.5 Hz, 1 H), 1.36 (s, 9 H); 13C NMR (100 MHz,
CDCl3) δ 157.0, 155.8, 147.8, 136.5, 129.8, 129.5, 128.8, 127.8, 127.2,
118.4, 58.2, 29.8; HRMS (EI) calcd for C14H16N2 213.1386, found
213.1391.
N-Allyl-N-phenylpyrido[1,2-a]indol-10-amine (56). This com-
pound was obtained as an orange oil (40.2 mg, 54%) and was highly
unstable in various solvents and neat. Because of the low stability, a
clean 13C NMR spectrum of this compound could not be obtained: 1H
NMR (400 MHz, CDCl3) δ 8.34 (d, J = 7.1 Hz, 1 H), 7.92 (d, J = 7.1
Hz, 1 H), 7.57 (d, J = 8.4 Hz, 1 H), 7.32 (d, J = 4.9 Hz, 2 H), 7.13
(t, J = 8.0 Hz, 2 H), 6.88−6.79 (m, 1 H), 6.70 (s, 3 H), 6.50 (s, 1 H),
6.12−5.97 (m, 1H), 5.31 (dd, J = 17.2, 1.7 Hz, 1 H), 5.14 (dd, J = 10.3,
tert-Butyl(thiazol-2-ylmethylene)amine (74). This compound
was obtained as a pale yellow liquid (198.3 mg, 69%): 1H NMR
2753
dx.doi.org/10.1021/jo2025543 | J. Org. Chem. 2012, 77, 2743−2755