E. V. Van der Eycken et al.
FULL PAPER
59.7, 55.9, 55.8, 52.9, 51.5, 51.4, 46.0, 28.3, 4.1 ppm. HRMS: calcd.
for C29H33N3O4 487.2471; found 487.2475.
(m, 0.64 H), 4.08 (d, J = 15.81 Hz, 0.68 H), 3.77 (s, 3 H), 2.42–
2.23 (m, 2 H), 1.19 (t, J = 7.53 Hz, 3 H), 1.13 (s, 9 H) ppm. 13C
NMR (75 MHz, CDCl3): δ = 167.4, 166.6, 159.3 (2), 155.9, 155.0,
140.4, 139.2, 134.2, 134.1, 133.9, 133.8, 129.7, 129.6, 129.3, 129.1,
128.4, 122.5, 122.2, 114.2 (2), 110.1, 110.0, 73.8, 72.8, 62.3, 59.3,
55.3, 52.7, 51.7, 51.5, 46.0, 28.3, 28.2, 12.8, 12.7 (2), 12.4 ppm.
HRMS: calcd. for C29H32ClN3O3 505.2132; found 505.2128.
N-{1-[2-(1H-Pyrrol-1-yl)phenyl]-2-(cyclohexylamino)-2-oxoethyl}-
N-(benzo[d][1,3]dioxol-5-ylmethyl)but-2-ynamide (5e): Off-white so-
1
lid (64% yield); m.p. 182–184 °C. H NMR (300 MHz, CDCl3): δ
= 7.80–7.31 (m, 3 H), 7.23–7.21 (m, 1 H), 6.68–6.60 (m, 4 H), 6.51–
6.44 (m, 1 H), 6.31–6.29 (m, 2 H), 6.02 (s, 0.40 H), 5.91 (s, 2 H),
5.57–5.43 (m, 1 H), 5.13 (s, 0.60 H), 4.91 (d, J = 16.20 Hz, 0.61
H), 4.66 (d, J = 14.31 Hz, 0.40 H), 4.04–3.98 (m, 1 H), 3.63–3.56
(m, 1 H), 2.01–1.89 (m, 3 H), 1.72–1.57 (m, 5 H), 1.30–0.72 (m, 5
H) ppm. 13C NMR (75 MHz, CDCl3): δ = 167.9, 167.1, 156.2,
155.1, 147.8, 147.2, 142.1, 140.9, 132.0, 131.7, 131.5, 130.8, 130.5,
130.1, 130.0, 129.2, 128.4, 128.3, 127.5, 122.4, 122.2, 121.8, 109.8,
109.7, 109.4, 108.4, 101.1, 91.9, 90.5, 73.7, 62.6, 59.4, 53.1, 48.4,
45.6, 32.6, 32.5, 25.5, 24.7, 24.6, 4.2 (2) ppm. HRMS: calcd. for
C30H31N3O4 497.2315; found 493.2318.
N-{2-(tert-Butylamino)-1-[5-chloro-2-(1H-pyrrol-1-yl)phenyl]-2-
oxoethyl}-N-(4-methoxybenzyl)but-2-ynamide (5j): Off-white solid
(49% yield); m.p. 142–144 °C. 1H NMR (300 MHz, CDCl3): δ =
7.74–7.29 (m, 2 H), 7.24–6.98 (m, 3 H), 6.80–6.60 (m, 4 H), 6.32–
6.30 (m, 2 H), 5.72 (s, 0.36 H), 5.31–5.27 (m, 1 H), 5.08 (s, 0.65
H), 5.03 (d, J = 16.38 Hz, 0.62 H), 4.38 (br. s, 0.4 H), 4.09 (d, J =
15.06 Hz, 1 H), 3.77 (s, 3 H), 2.03–1.91 (m, 3 H), 1.13 (s, 9 H) ppm.
13C NMR (75 MHz, CDCl3): δ = 167.3, 166.5, 159.3 (2), 155.8,
154.9, 140.3, 139.2, 134.1 (2), 133.9, 133.8, 130.8, 130.5, 130.1,
129.6, 129.5, 129.3, 129.1, 128.4 (2), 122.4, 122.3, 114.2, 110.0, 92.1,
90.8, 73.7, 72.8, 62.3, 59.3, 55.3, 52.7, 51.7, 51.5, 46.1, 28.3, 28.1,
4.2 ppm. HRMS: calcd. for C28H30ClN3O3 491.1976; found
491.1974.
N-{1-[2-(1H-Pyrrol-1-yl)phenyl]-2-(tert-butylamino)-2-oxoethyl}-
N-(benzo[d][1,3]dioxol-5-ylmethyl)pent-2-ynamide (5f): Off-white so-
1
lid (56% yield); m.p. 159–161 °C. H NMR (300 MHz, CDCl3): δ
= 7.80–7.31 (m, 3 H), 7.22–7.19 (m, 1 H), 6.70–6.29 (m, 7 H), 5.90
(s, 2 H), 5.85 (s, 0.40 H), 5.49–5.38 (m, 1 H), 5.11 (s, 0.60 H), 4.96
(d, J = 15.84 Hz, 0.61 H), 4.55 (d, J = 15.24 Hz, 0.40 H), 4.11–
3.98 (m, 1 H), 2.38–2.22 (m, 2 H), 1.18–1.09 (m, 12 H) ppm. 13C
N-{1-[2-(1H-Pyrrol-1-yl)phenyl]-2-(tert-butylamino)-2-oxoethyl}-
N-(4-methoxybenzyl)-3-phenylpropiolamide (5k): Brown solid (57%
yield); m.p. 155–157 °C. 1H NMR (300 MHz, CDCl3): δ = 7.86–
NMR (75 MHz, CDCl3): δ = 172.4, 168.2, 167.3, 161.5, 155.1, 7.31 (m, 8 H), 7.23–6.84 (m, 3 H), 6.77–6.59 (m, 4 H), 6.32–6.25
147.8, 147.2, 142.3, 140.9, 132.1, 131.8, 131.6, 130.8, 130.5, 130.4,
129.9, 129.2, 128.5, 128.3, 128.2, 127.4, 122.5, 122.4, 122.2, 121.8,
109.6, 108.4, 108.2, 101.1 (2), 97.0, 95.6, 62.6, 59.8, 53.0, 51.4, 45.6,
(m, 2 H), 5.89 (s, 0.38 H), 5.41–5.32 (m, 1 H), 5.19 (s, 0.62 H), 5.11
(d, J = 15.24 Hz, 0.70 H), 4.57 (d, J = 15.24 Hz, 0.30 H), 4.25–
4.16 (m, 1 H), 3.81–3.76 (m, 3 H), 1.18–1.08 (m, 9 H) ppm. 13C
28.4, 12.8, 12.7, 12.6 ppm. HRMS: calcd. for C28H31N3O4 NMR (75 MHz, CDCl3): δ = 168.2, 167.2, 159.3, 156.0, 155.0,
485.2315; found 485.2288.
142.3, 140.9, 132.6, 132.5, 132.0, 131.7, 130.8, 130.6, 130.4, 130.3,
130.2, 129.9, 129.8, 129.5, 129.4, 129.3, 128.6 (2), 128.5, 128.4,
128.3, 127.4, 126.0, 123.6, 122.4, 122.1, 120.2, 120.1, 114.1 (2),
113.8, 113.1, 110.5, 109.9, 109.6, 92.4, 91.2, 82.1, 81.0, 62.9, 59.8,
55.3, 52.6, 51.5 (2), 45.6, 28.3, 28.2 ppm. HRMS: calcd. for
C33H33N3O3 519.2522; found 519.2540.
N-{1-[2-(1H-Pyrrol-1-yl)phenyl]-2-(p-tolylamino)-2-oxoethyl}-N-
(4-methoxybenzyl)but-2-ynamide (5g): Grey solid (49% yield); m.p.
202–204 °C. 1H NMR (300 MHz, CDCl3): δ = 7.90–7.34 (m, 3 H),
7.23–7.22 (m, 1 H), 7.12–6.98 (m, 6 H), 6.76–6.63 (m, 4 H), 6.33–
6.30 (m, 2 H), 6.12 (s, 0.24 H), 5.30 (s, 0.77 H), 5.03 (d, J =
15.62 Hz, 0.72 H), 4.65 (d, J = 14.85 Hz, 0.28 H), 4.28 (d, J = N-{2-(Butylamino)-1-[5-chloro-2-(1H-pyrrol-1-yl)phenyl]-2-
14.49 Hz, 0.29 H), 4.12 (d, J = 15.45 Hz, 0.71 H), 3.75 (s, 3 H),
2.28–2.27 (m, 3 H), 2.02–1.87 (s, 3 H) ppm. 13C NMR (75 MHz,
CDCl3): δ = 167.2, 166.4, 159.4, 156.1, 155.3, 142.0, 141.0, 134.9,
133.9, 131.5, 131.0, 130.4, 130.0, 129.7, 129.4, 129.3, 129.2, 128.5,
128.4, 128.2, 127.6, 122.5, 122.3, 120.1, 119.8, 114.2, 109.9, 91.0,
73.7, 63.0, 59.7, 55.3, 52.6, 45.7, 20.9, 4.2 ppm. HRMS: calcd. for
C31H29N3O3 491.2209; found 491.2234.
oxoethyl}-N-(4-methoxybenzyl)-3-phenylpropiolamide (5l): Brown
solid (33% yield); m.p. 53–55 °C. H NMR (300 MHz, CDCl3): δ
1
= 7.83–7.33 (m, 7 H), 7.21–7.04 (m, 3 H), 6.79–6.57 (m, 4 H), 6.33–
6.24 (m, 2 H), 5.98 (s, 0.31 H), 5.52–5.50 (m, 1 H), 5.24 (s, 0.69
H), 5.08 (d, J = 15.99 Hz, 0.68 H), 4.59 (d, J = 16.02 Hz, 0.32 H),
4.42 (d, J = 14.52 Hz, 0.33 H), 4.24 (d, J = 15.81 Hz, 0.67 H), 3.77
(s, 3 H), 3.11–3.02 (m, 2 H), 1.21–1.16 (m, 4 H), 0.88–0.79 (m, 3
H) ppm. 13C NMR (75 MHz, CDCl3): δ = 168.1, 167.4, 159.4,
159.2, 155.9, 155.1, 139.3, 134.1, 133.8, 132.6 (2), 130.8, 130.5 (2),
130.4, 130.2, 129.4, 128.6, 128.5, 128.1, 122.5, 122.2, 120.0, 119.9,
114.1, 114.0, 110.3, 110.1, 91.8, 81.8, 62.0, 58.8, 55.3, 52.8, 39.6,
31.1, 29.7, 19.9, 19.8, 13.7, 13.6 ppm. HRMS: calcd. for
C33H32ClN3O3 553.2132; found 553.2143.
N-(Benzo[d][1,3]dioxol-5-ylmethyl)-N-{2-(tert-butylamino)-1-[5-
chloro-2-(1H-pyrrol-1-yl)phenyl]-2-oxoethyl}but-2-ynamide (5h):
White solid (49% yield); m.p. 172–174 °C. 1H NMR (300 MHz,
CDCl3): δ = 7.73–7.30 (m, 2 H), 7.22–7.12 (m, 1 H), 6.72–6.63 (m,
3 H), 6.48–6.45 (m, 1 H), 6.34–6.31 (m, 2 H), 5.93–5.92 (m, 2 H),
5.72 (s, 0.29 H), 5.44–5.33 (m, 1 H), 5.07 (s, 0.72 H), 4.98 (d, J =
15.81 Hz, 0.73 H), 4.36 (s, 0.55 H), 4.00 (d, J = 15.63 Hz, 0.73 H), N-{1-[2-(1H-Pyrrol-1-yl)phenyl]-2-(tert-butylamino)-2-oxoethyl}-
2.03–1.92 (m, 3 H), 1.16 (s, 9 H) ppm. 13C NMR (75 MHz, CDCl3):
δ = 167.2, 166.5, 155.8, 154.9, 148.1, 148.0, 147.4, 147.2, 139.2,
134.1, 133.9, 133.7, 131.1, 130.8, 130.5, 130.0, 129.6, 129.3, 129.1,
128.4, 122.4, 122.2, 122.1, 121.7, 110.1, 109.1, 108.4, 108.3, 108.2,
N-(4-methoxybenzyl)propiolamide (5m): Brown solid (59% yield);
m.p. 49–51 °C. H NMR (300 MHz, CDCl3): δ = 7.79–7.31 (m, 3
H), 7.22–7.20 (m, 1 H), 7.00–6. 27 (m, 8 H), 5.88 (s, 0.35 H), 5.31
(br. s, 1 H), 5.10 (s, 0.65 H), 5.03 (d, J = 15.63 Hz, 0.67 H), 4.60
1
101.2, 92.3, 91.0, 73.5, 72.7, 62.2, 59.4, 53.1, 51.7, 51.5, 46.5, 28.3, (d, J = 14.82 Hz, 0.33 H), 4.22–4.10 (m, 1 H), 3.81–3.76 (m, 3 H),
4.2 ppm. HRMS: calcd. for C28H28ClN3O4 505.1768; found
505.1786.
3.18–3.12 (m, 1 H), 1.15 (s, 9 H) ppm. 13C NMR (75 MHz, CDCl3):
δ = 167.9, 166.8, 159.3, 159.2, 155.0, 153.7, 142.2, 140.9, 131.8,
131.4, 130.6, 130.4, 130.0, 129.5, 129.4, 129.3, 128.5, 128.4, 128.3,
128.0, 127.4, 122.3, 122.1, 109.9, 109.8, 80.9, 80.0, 76.2, 74.8, 62.7,
60.4, 59.7, 55.3, 52.5, 51.7, 51.5, 45.6, 28.3 ppm. HRMS: calcd. for
C27H29N3O3 443.2209; found 443.2197.
N-{2-(tert-Butylamino)-1-[5-chloro-2-(1H-pyrrol-1-yl)phenyl]-2-
oxoethyl}-N-(4-methoxybenzyl)pent-2-ynamide (5i): White solid
(45% yield); m.p. 153–155 °C. 1H NMR (300 MHz, CDCl3): δ =
7.75–7.30 (m, 2 H), 7.22–7.11 (m, 1 H), 7.03–6.99 (m, 2 H), 6.79–
6.59 (m, 4 H), 6.32–6.30 (m, 2 H), 5.71 (s, 0.35 H), 5.32–5.30 (m,
1 H), 5.07 (s, 0.65 H), 5.04 (d, J = 15.81 Hz, 0.63 H), 4.45–4.30
N-{1-[2-(1H-Pyrrol-1-yl)phenyl]-2-(tert-butylamino)-2-oxoethyl}-
N-benzylpropiolamide (5n): White solid (54 % yield); m.p. 142–
2088
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Eur. J. Org. Chem. 2014, 2084–2091