H. Maus et al.
Bioorganic & Medicinal Chemistry 47 (2021) 116392
125.7, 123.8, 120.4, 106.2, 104.3, 55.9 ppm. MS (ESI) m/z [M + H+]
calcd for C17H15NO3S 314.1, found 314.2.
phenylpyrrolidine-2-carboxamide (35b): 150 mg, 0.39 mmol, yield:
54%. mp: 209–211 ◦C. Rf = 0.28 (CH/EtOAc 2:1). [
α
]
20 = –6 (c = 5 in
5,6-Dimethoxy-N-phenylbenzofuran-2-carboxamide (33e): 180
mg, 0.61 mmol, yield: 90%. mp: 187–189 ◦C. Rf = 0.37 (CH/EtOAc 2:1).
1H NMR: (300 MHz, DMSO‑d6): δ = 10.33 (s, 1H), 7.81 (d, J = 7.7 Hz,
2H), 7.67 (s, 1H), 7.36 (t, J = 7.7 Hz, 2H), 7.32–7.24 (m, 2H), 7.11 (d, J
= 7.7 Hz, 1H), 3.86 (s, 3H), 3.82 (s, 3H) ppm. 13C NMR: (75 MHz,
DMSO‑d6): δ = 156.7, 150.3, 149.8, 147.7, 147.2, 138.6, 128.7, 123.8,
120.4, 118.9, 111.1, 103.3, 95.5, 56.0, 55.9 ppm. MS (ESI) m/z [M +
H+] calcd for C17H15NO4 298.10 (100%), 299.10 (18.4%), 300.11
(1.6%), found 298.18 (100%), 299.18 (16.7%), 300.17 (1.0%); purity
(HPLC) = 99%.
DMSO). 1H NMR: (300 MHz, DMSO‑d6): δ = 10.21 (s,D1H), 8.05 (d, J =
9.0 Hz, 1H), 7.78–7.57 (m, 2H), 7.55–7.48 (m, 1H), 7.34–7.17 (m, 3),
7.14–6.95 (m, 1H), 5.58–5.39 (m, 1H), 4.34–4.17 (m, 1H), 3.84 (s, 3H),
3.78–3.64 (m, 1H), 2.47–1.85 (m, 4H) ppm. 13C NMR: (75 MHz,
DMSO‑d6): δ = 170.9, 169.9, 159.0, 147.6, 147.2, 139.3, 128.7, 125.3,
124.8, 123.3, 119.3, 117.0, 104.3, 62.2, 55.8, 49.6, 32.2, 21.7 ppm. MS
(ESI) m/z [M + H+] calcd for C20H19N3O3S 382.1, found 382.1.
(S)-1-(5,6-Dimethoxy-1H-indole-2-carbonyl)-N-phenyl-
pyrrolidine-2-carboxamide (35c): 250 mg, 0.63 mmol, yield: 93%.
20
mp: 113–115 ◦C. Rf = 0.33 (CH/EtOAc 1:2). [
α
]
= –62 (c = 5 in
D
6,7-Dimethoxy-N-phenylquinoline-3-carboxamide (33f): 140
DMSO). 1H NMR: (300 MHz, DMSO‑d6): δ = 11.26 (s, 1H), 10.10 (s, 1H),
7.71–7.53 (m, 2H), 7.36–7.24 (m, 2H), 7.14–7.00 (m, 2H), 6.96–6.88
(m, 2H), 4.74–4.64 (m, 1H), 4.09–3.85 (m, 2H), 3.40 (s, 6H), 2.31–2.06
(m, 1H), 2.06–1.89 (m, 3H) ppm. 13C NMR: (75 MHz, DMSO‑d6): δ =
170.8, 160,4, 148.7, 145.3, 139.3, 131.1, 129.0, 128.7, 123.2, 120.2,
119.2, 105.4, 102.8, 94.5, 61.7, 55.7, 55.4, 48.8, 29.1, 25.1 ppm. MS
(ESI) m/z [M + H+] calcd for C22H23N3O4 394.2, found 394.2.
◦
mg, 0.45 mmol, yield: 70%. mp: 201–203 C. Rf = 0.53 (DCM/MeOH
19:1). 1H NMR: (300 MHz, DMSO‑d6): δ = 10.48 (s, 1H), 9.17 (d, J = 2.2
Hz, 1H), 8.74 (d, J = 2.2 Hz, 1H), 7.82 (d, J = 7.7 Hz, 2H), 7.49 (s, 1H),
7.47 (s, 1H), 7.38 (t, J = 7.7 Hz, 2H), 7.13 (t, J = 7.7 Hz, 1H), 3.98 (s,
3H), 3.94 (s, 3H) ppm. 13C NMR: (75 MHz, DMSO‑d6): δ = 164.4, 153.6,
150.0, 146.5, 146.1, 139.1, 134.1, 128.7, 125.8, 123.8, 122.1, 120.3,
107.5, 106.4, 55.9, 55.8 ppm. MS (ESI) m/z [M + H+] calcd for
(S)-1-(5,6-Dimethoxybenzo[b]thiophene-2-carbonyl)-N-phe-
nylpyrrolidine-2-carboxamide (35d): 210 mg, 0.50 mmol, yield: 99%.
C
17H15NO4 298.1, found 298.2.
5-Methoxy-N-phenylbenzofuran-2-carboxamide (33g): 170 mg,
mp: 95–97 ◦C. Rf = 0.13 (CH/EtOAc 2:1). [
α]
20 = –16 (c = 5 in MeCN).
0.64 mmol, yield: 94%. mp: 168–170 ◦C. Rf = 0.40 (CH/EtOAc 4:1). 1H
NMR: (300 MHz, DMSO‑d6) δ = 10.48 (s, 1H), 7.87–7.77 (m, 2H),
7.73–7.66 (m, 3H), 7.62 (d, J = 9.1 Hz, 1H), 7.42–7.33 (m, 2H),
7.34–7.27 (m, 2H), 7.18–7.04 (m, 2H), 3.81 (s, 3H) ppm. 13C NMR: (75
MHz, DMSO‑d6) δ = 156.7, 156.1, 149.4, 138.4, 128.7, 127.8, 124.1,
120.5, 116.5, 112.6, 110.8, 104.2, 55.6 ppm.
1H NMR: (300 MHz, DMSO‑d6): δ = 10.10 (s,D1H), 7.90 (s, 1H), 7.62 (d,
J = 7.7 Hz, 2H), 7.55 (s, 1H), 7.45 (s, 1H), 7.30 (d, J = 7.7 Hz, 2H), 7.04
(t, J = 7.7 Hz, 1H), 4.70–4.60 (m, 1H), 4.04–3.92 (m, 2H), 3.84 (s, 3H),
3.83 (s, 3H), 2.33–2.22 (m, 1H), 2.18–2.06 (m, 1H), 2.05–1.89 (m, 2H)
ppm. 13C NMR: (75 MHz, DMSO‑d6): δ = 170.4, 161.1, 149.8, 148.3,
139.2, 136.9, 133.5, 132.8, 128.7, 126.8, 123.2, 119.2, 106.3, 103.9,
62.0, 55.8, 55.6, 49.4, 29.2, 25.2 ppm. MS (ESI) m/z [M + H+] calcd for
6-Methoxy-N-phenylbenzofuran-2-carboxamide (33h): 165 mg,
0.62 mmol, yield: 91%. mp: 134–136 ◦C. Rf = 0.4 (CH/EtOAc 4:1). 1H
NMR: (300 MHz, DMSO‑d6) δ = 10.37 (s, 1H), 7.86–7.76 (m, 2H),
7.74–7.64 (m, 2H), 7.36 (dd, J = 8.6, 7.3 Hz, 2H), 7.30–7.23 (m, 1H),
7.17–7.06 (m, 1H), 6.99 (dd, J = 8.6, 2.3 Hz, 1H), 3.85 (s, 3H) ppm. 13C
NMR: (75 MHz, DMSO‑d6) δ = 159.7, 156.7, 155.8, 148.0, 138.5, 128.7,
123.9, 123.2, 120.4, 120.3, 113.4, 110.8, 95.9, 55.7 ppm.
C22H22N2O4S 411.1, found 411.2.
(S)-1-(5,6-Dimethoxybenzofuran-2-carbonyl)-N-phenyl-
pyrrolidine-2-carboxamide (35e): 250 mg, 0.63 mmol, yield: 93%.
20
mp: 184–186 ◦C. Rf = 0.17 (CH/EtOAc 1:2). [
α
]
= –80 (c = 5 in
MeCN). 1H NMR: (300 MHz, DMSO‑d6): δ = 10.11 (Ds, 1H), 7.67–7.55 (m,
2H), 7.44 (s, 1H), 7.36–7.24 (m, 3H), 7.15 (s, 1H), 7.01–6.98 (m, 1H),
4.72–4.62 (m, 1H), 4.05–3.97 (m, 2H), 3.84 (s, 3H), 3.80 (s, 3H),
2.33–2.18 (m, 1H), 2.16–1.83 (m, 3H) ppm. 13C NMR: (75 MHz,
DMSO‑d6): δ = 170.4, 157.6, 150.1, 149.5, 147.8, 147.1, 139.2, 128.7,
123.2, 119.2, 118.6, 112.5, 103.1, 95.5, 61.6, 61.3, 59.8, 56.0, 55.8,
48.6, 48.1, 32.3, 29.0, 25.0, 21.7, 20.7, 14.1 ppm. MS (ESI) m/z [M +
H+] calcd for C22H22N2O5 395.15 (100%), 396.16 (23.8%), 397.16
(2.7%), found 395.20 (100%), 396.17 (26.7%), 397.16 (2.4%); purity
(HPLC) = 99%.
4,6-Dimethoxy-N-phenylbenzofuran-2-carboxamide (33i): 160
mg, 0.54 mmol, yield: 79%. mp: 144–146 ◦C. Rf = 0.25 (CH/EtOAc 4:1).
1H NMR: (300 MHz, DMSO‑d6) δ = 10.25 (s, 1H), 7.84–7.75 (m, 2H),
7.76–7.70 (m, 2H), 7.41–7.30 (m, 2H), 7.16–7.05 (m, 1H), 6.89–6.83
(m, 2H), 6.49 (d, J = 1.9 Hz, 1H), 3.91 (s, 3H), 3.84 (s, 3H) ppm. 13
C
NMR: (75 MHz, DMSO‑d6) δ = 161.2, 156.6, 154.2, 146.6, 138.6, 128.7,
123.8, 120.3, 111.1, 108.1, 95.2, 88.5, 55.9, 55.8, 52.8 ppm.
6-Methoxy-5-nitro-N-phenylbenzofuran-2-carboxamide (33j):
760 mg, 2.4 mmol, yield: 97%. mp: 184–186 ◦C. Rf = 0.44 (CH/EtOAc
(S)-1-(6,7-Dimethoxyquinoline-3-carbonyl)-N-phenyl-
1
2:1). H NMR: (300 MHz, DMSO‑d6): δ = 10.51 (s, 1H), 8.44 (s, 1H),
pyrrolidine-2-carboxamide (35f): 30 mg, 0.57 mmol, yield: 89%. mp:
20
7.85 (d, J = 0.9 Hz, 1H), 7.81–7.73 (m, 2H), 7.67 (d, J = 0.9 Hz, 1H),
7.43–7.32 (m, 2H), 7.20–7.08 (m, 1H), 4.00 (s, 3H) ppm. 13C NMR: (75
MHz, DMSO‑d6): δ = 157.2, 156.5, 152.7, 150.6, 138.7, 138.5, 129.2,
124.7, 121.0, 120.4, 119.8, 111.3, 98.0, 57.8 ppm.
112–114 ◦C. Rf = 0.18 (DCM/MeOH 49:1). [
α
]
= –44 (c = 5 in
D
MeCN). 1H NMR: (300 MHz, DMSO‑d6): δ = 10.13 (s, 1H), 8.83 (d, J =
2.1 Hz, 1H), 8.46 (d, J = 2.1 Hz), 7.65 (t, J = 7.8 Hz, 2H), 7.48 (s, 1H),
7.42 (s, 1H), 7.32 (t, J = 7.8 Hz, 2H), 7.05 (t, J = 7.8 Hz, 1H), 4.73–4.62
(m, 1H), 3.96 (s, 3H), 3.92 (s, 3H), 3.74–3.60 (m, 2H), 2.38–2.25 (m,
1H), 2.38–2.04 (m, 3H) ppm. 13C NMR: (75 MHz, DMSO‑d6): δ = 170.4,
166.7, 153.3, 150.0, 146.3, 145.2, 139.2, 133.2, 128.7, 127.2, 123.2,
122.0, 119.2, 107.4, 106.3, 61.0, 55.8, 54.9, 29.8, 25.2. MS (ESI) m/z
[M + H+] calcd for C23H23N3O4 406.2, found 406.2.
5,6-Dimethoxy-N-(4-iodophenyl)benzo[d]thiazole-2-carbox-
◦
amide (33k): 230 mg, 0.52 mmol, yield: 76%. mp: 181–185 C. Rf =
0.55 (CH/EtOAc 2:1). 1H NMR: (300 MHz, DMSO‑d6): δ = 10.96 (s, 1H),
7.78–7.67 (m, 5H), 7.57 (s, 1H), 3.89 (d, J = 2.0 Hz, 6H) ppm. 13C NMR:
(75 MHz, DMSO‑d6): δ = 161.4, 158.4, 150.0, 150.0, 146.9, 137.9,
137.4, 129.5, 122.7, 104.9, 103.5, 88.3, 56.0, 55.8 ppm.
(S)-1-(4,6-Dimethoxybenzofuran-2-carbonyl)-N-phenyl-
(S)-1-(5,6-Dimethoxybenzo[d]thiazole-2-carbonyl)-N-phenyl-
pyrrolidine-2-carboxamide (35i): 260 mg, 0.67 mmol, yield: 98%. mp:
pyrrolidine-2-carboxamide (35a): 210 mg, 0.51 mmol, yield: 81%.
125–128 ◦C. Rf = 0.43 (CH/EtOAc 1:2). [
α
]
D
20 = –50 (c = 5 in MeOH).
mp: 237–239 ◦C. Rf = 0.47 (CH/EtOAc 1:2). [
α]
D
= –10 (c = 5 in
1H NMR: (300 MHz, DMSO‑d6): δ = 1H NMR: (300 MHz, DMSO‑d6) δ =
10.36–9.96 (m, 1H), 7.66–7.52 (m, 2H), 7.41–7.23 (m, 3H), 7.09–6.99
(m, 1H), 6.88 (s, 1H), 6.50–6.35 (m, 1H), 5.14–4.59 (m, 1H), 4.09–3.94
(m, 1H), 3.93–3.63 (m, 6H), 2.46–1.82 (m, 4H) ppm. 13C NMR: (75
MHz, DMSO‑d6): δ = 170.3, 161.0, 157.4, 156.2, 154.1, 146.7, 139.1,
128.7, 123.2, 119.3, 119.2, 110.8, 109.2, 95.1, 88.3, 61.6, 61.3, 55.9,
55.7, 48.6, 48.2, 32.3, 29.0, 25.0, 21.7 ppm.
20
DMSO). 1H NMR: (300 MHz, DMSO‑d6): δ = 10.2 (s, 1H), 7.74–7.52 (m,
3H), 7.38–7.20 (m, 3H), 7.11–6.39 (m, 1H), 4.76–4.56 (m, 1H),
4.36–4.23 (m, 1H), 3.88 (s, 3H), 3.82 (s, 3H), 3.79–3.72 (m, 1H),
2.37–1.82 (m, 4H) ppm. 13C NMR: (75 MHz, DMSO‑d6): δ = 171.2,
169.0, 159.0, 149.9, 149.7, 147.5, 139.5, 128.7, 128.5, 123.3, 119.2,
105.5, 103.2, 62.3, 55.9, 55.5, 48.7, 32.1, 21.8 ppm. MS (ESI) m/z [M +
H+] calcd for C21H21N3O4S 412.1, found 412.1.
(S)-1-(6,7-Dimethoxy-2-naphthoyl)-N-phenylpyrrolidine-2-car-
(S)-1-(6-Methoxybenzo[d]thiazole-2-carbonyl)-N-
boxamide (35m): 150 mg, 0.37 mmol, yield: 86%. mp: 173–175 ◦C. Rf
16