Vol. 65, No. 2 (2017)
Chem. Pharm. Bull.
183
361.4 [M+H]+. Anal. Calcd for C20H28N2O4: C 66.64, H 7.83, Calcd for C15H13ClN2O2: C 62.40, H 4.54, Cl 12.28, N 9.70, O
N 7.77, O 17.76; Found: C 66.56, H 7.80, N 7.83, O 17.69.
(E)-5-((3,4-Dihydro-2H-benzo[b][1,4]dioxepin-7-yl)-
methyleneamino)pyrimidin-2(1H)-one (2F)
11.08; Found: C 62.47, H 4.55, Cl 12.34, N 9.62, O 11.08.
(E)-N-((3,4-Dihydro-2H-benzo[b][1,4]dioxepin-7-yl)-
methylene)-5-(trifluoromethyl)pyridin-2-amine (2K)
White solid; yield 79%. Rf=0.3 (4:1 hexane–EtOAc); mp:
White solid; yield: 89%. Rf=0.5 (4:1 hexane–EtOAc); mp:
121.4–122.3°C. 1H-NMR (400MHz, DMSO-d6) δ: 8.17 (s, 127.5–128.1°C. H-NMR (400MHz, DMSO-d6) δ: 8.51 (s, 1H),
1H), 8.01 (s, 1H), 7.31 (d, J=7.0Hz, 1H), 7.08 (d, J=8.0Hz, 8.03–7.96 (m, 1H), 7.70 (dd, J=8.9, 2.4Hz, 1H), 7.08–6.92
1H), 6.85 (s, 2H), 5.56 (d, J=7.0Hz, 1H), 4.21 (dt, J=10.8, (m, 2H), 6.73 (d, J=8.9Hz, 1H), 6.62 (dd, J=5.4, 1.7Hz,
5.6Hz, 4H), 2.15 (dt, J=11.0, 5.6Hz, 2H). 13C-NMR (100MHz, 1H)4.11 (dd, J=8.4, 5.3Hz, 4H), 2.10 (dd, J=10.9, 5.5Hz, 2H).
DMSO-d6) δ: 163.72, 158.81, 155.19, 154.24, 148.90, 132.39, 13C-NMR (100MHz, DMSO-d6) δ: 162.61, 159.95, 156.70,
128.93, 124.08, 122.26, 121.65, 105.49, 70.87, 70.85, 31.55. 151.26, 150.94, 146.17, 134.37, 132.28, 125.66, 122.98, 122.15,
MS (ESI): m/z 272.3 [M+H]+. Anal. Calcd for C14H13N3O3: C 120.13, 114.13, 70.82, 70.76, 31.96. MS (ESI): m/z 322.3
61.99, H 4.83, N 15.49, O 17.69; Found: C 62.04, H 4.83, N [M+H]+. Anal. Calcd for C16H13F3N2O2: C 59.63, H 4.07, F
1
15.41, O 17.75.
17.68, N 8.69, O 9.93; Found: C 59.68, H 4.09, F 17.53, N 8.73,
(E)-N-((3,4-Dihydro-2H-benzo[b][1,4]dioxepin-7-yl)- O 9.89.
methylene)pyrimidin-4-amine (2G)
(E)-6-((3,4-Dihydro-2H-benzo[b][1,4]dioxepin-7-yl)-
White solid; yield: 93%. Rf=0.4 (4:1 hexane–EtOAc); mp: methyleneamino)nicotinonitrile (2L)
1
143.7–144.5°C. H-NMR (400MHz, DMSO-d6) δ: 8.61 (s, 1H),
Yellow solid; yield: 77%. Rf=0.4 (4:1 hexane–EtOAc); mp:
1
8.32 (s, 1H), 8.03 (d, J=5.9Hz, 1H), 7.46 (d, J=2.1Hz, 1H), 115.4–116.3°C. H-NMR (400MHz, DMSO-d6) δ: 9.05 (s, 1H),
7.35 (dd, J=8.3, 2.0Hz, 1H), 6.98 (d, J=8.2Hz, 1H), 6.40 (dd, 8.48 (ddd, J=4.8, 1.9, 0.8Hz, 1H), 7.88 (dd, J=1.8, 1.2Hz,
J=5.9, 1.3Hz, 1H), 4.24 (dt, J=11.6, 5.7Hz, 4H), 2.23 (m, 2H). 1H), 7.61 (s, 1H), 7.33–7.31 (m, 1H), 7.13–7.06 (m, 1H), 6.45
13C-NMR (100MHz, DMSO-d6) δ: 167.20, 164.34, 158.36, (ddd, J=7.1, 5.0, 1.0Hz, 1H), 4.29–4.16 (m, 4H), 2.22 - 2.10
154.21, 143.07, 131.28, 129.20, 124.38, 122.20, 121.80, 115.01, (m, 2H). 13C-NMR (101MHz, DMSO-d6) δ: 161.82, 160.23,
70.42, 70.38, 31.27. MS (ESI): m/z 256.1 [M+H]+. Anal. Calcd 154.80, 151.43, 149.25, 148.17, 139.01, 137.36, 131.52, 125.35,
for C14H13N3O2: C 65.87, H 5.13, N 16.46, O 12.54; Found: C 122.61, 119.93, 112.23, 70.87, 70.76, 31.41. MS (ESI): m/z 280.1
65.91, H 5.10, N 14.48, O 12.59.
(E)-N-((3,4-Dihydro-2H-benzo[b][1,4]dioxepin-7-yl)- 15.05, O 11.46; Found: C 68.87, H 4.73, N 14.96, O 11.37.
methylene)pyridin-3-amine (2H) (E)-4-Chloro-N-((3,4-dihydro-2H-benzo[b][1,4]dioxepin-7-
White solid; yield 90%. Rf=0.4 (4:1 hexane–EtOAc); mp: yl)methylene)pyridin-2-amine (2M)
135.9–136.4°C. 1H-NMR (400MHz, DMSO-d6) δ: 8.58 (s,
White solid; yield 92%. Rf=0.4 (4:1 hexane–EtOAc); mp:
[M+H]+. Anal. Calcd for C16H13N3O2: C 68.81, H 4.69, N
1
1H), 8.46 (ddd, J=6.2, 3.6, 1.0Hz, 2H), 7.67 (ddd, J=8.1, 2.6, 105.8–106.4°C. H-NMR (400MHz, DMSO-d6) δ: 9.03 (s, 1H),
1.5Hz, 1H), 7.59–7.52 (m, 2H), 7.48–7.39 (m, 1H), 7.13–7.06 8.46 (dd, J=4.3, 1.7Hz, 1H), 7.63 (dd, J=6.9, 1.9Hz, 2H), 7.11
(m, 1H), 4.22 (dt, J=13.1, 5.8Hz, 4H), 2.20–2.12 (m, 2H). (d, J=8.9Hz, 1H), 6.66 (d, J=1.7Hz, 1H), 6.61 (dd, J=5.5,
13C-NMR (100MHz, DMSO-d6) δ: 162.13, 154.58, 151.41, 1.9Hz, 1H), 4.23 (ddd, J=11.4, 8.4, 3.7Hz, 4H), 2.22–2.12 (m,
147.70, 147.31, 143.38, 131.70, 128.09, 124.84, 124.47, 122.38, 2H). 13C-NMR (100MHz, DMSO-d6) δ: 163.50, 161.40, 155.14,
122.33, 70.92, 70.84, 31.44. MS (ESI): m/z 255.3 [M+H]+. 151.40, 150.56, 149.87, 144.77, 128.80, 125.64, 122.86, 119.30,
Anal. Calcd for C15H14N2O3: C 70.85, H 5.55, N 11.02, O 12.58; 112.17, 70.88, 70.73, 31.32. MS (ESI): m/z 289.4 [M+H]+.
Found: C 70.76, H 5.59, N 11.16, O 12.41.
Anal. Calcd for C15H13ClN2O2: C 62.40, H 4.54, Cl 12.28, N
(E)-N-((3,4-Dihydro-2H-benzo[b][1,4]dioxepin-7-yl)- 9.70, O 11.08; Found: C 62.45, H 4.57, Cl 12.23, N 9.68, O
methylene)pyridin-2-amine (2I)
11.12.
(E)-N-((3,4-Dihydro-2H-benzo[b][1,4]dioxepin-7-yl)-
White solid; yield: 84%. Rf=0.4 (4:1 hexane–EtOAc); mp:
1
145.3–145.7°C. H-NMR (400MHz, DMSO-d6) δ: 9.01 (s, 1H), methylene)-4-methylpyridin-2-amine (2N)
8.39 (dd, J=8.3, 1.7Hz, 1H), 7.53 (ddd, J=8.2, 5.9, 3.1Hz,
White solid; yield: 88%. Rf=0.5 (4:1 hexane–EtOAc); mp:
1H), 7.36–7.26 (m, 2H), 7.19–7.11 (m, 1H), 7.08–6.94 (m, 1H), 153.3–153.6°C. 1H-NMR (400MHz, DMSO-d6) δ: 9.05 (s,
6.89–6.81 (m, 1H), 4.23 (dd, J=11.0, 5.5Hz, 4H), 2.17 (td, 1H), 8.33 (d, J=5.0Hz, 1H), 7.75 (d, J=5.2Hz, 1H), 7.61 (dd,
J=9.8, 5.5Hz, 2H). 13C-NMR (100MHz, DMSO-d6) δ: 162.24, J=6.9, 1.9Hz, 2H), 7.18–7.03 (m, 1H), 6.31 (d, J=5.2Hz, 1H),
156.68, 154.34, 151.47, 150.29, 145.68, 142.84, 137.90, 129.22, 4.23 (dt, J=13.6, 5.6Hz, 4H), 2.36 (s, 3H), 2.15 (dd, J=11.2,
127.22, 125.03, 122.97, 115.22, 70.92, 70.79, 30.95. MS (ESI): 5.6Hz, 2H). 13C-NMR (100MHz, DMSO-d6) δ: 161.60, 160.33,
m/z 255.3 [M+H]+. Anal. Calcd for C15H14N2O3: C 70.85, H 154.73, 151.43, 149.79, 148.85, 147.84, 131.59, 125.27, 122.51,
5.55, N 11.02, O 12.58; Found: C 70.92, H 5.54, N 11.08, O 120.50, 113.81, 70.86, 70.74, 31.42, 21.01. MS (ESI): m/z 269.2
12.50.
(E)-5-Chloro-N-((3,4-dihydro-2H-benzo[b][1,4]dioxepin-7- 10.44, O 11.93; Found: C 71.68, H 6.11, N 10.39, O 11.88.
yl)methylene)pyridin-2-amine (2J) (E)-N-((3,4-Dihydro-2H-benzo[b][1,4]dioxepin-7-yl)-
White solid; yield: 85%. Rf=0.4 (4:1 hexane–EtOAc); methylene)-3-methylpyridin-2-amine (2O)
mp: 138.2–138.8°C. 1H-NMR (400MHz, DMSO-d6) δ: 9.03
White solid; yield: 86%. Rf=0.5 (4:1 hexane–EtOAc); mp:
[M+H]+. Anal. Calcd for C15H16N2O2: C 71.62, H 6.01, N
1
(s, 1H), 8.52 (d, J=2.6Hz, 1H), 7.62 (dd, J=7.5, 1.7Hz, 2H), 145.8–146.1°C. H-NMR (400MHz, DMSO-d6) δ: 8.99 (s, 1H),
7.36 (d, J=8.5Hz, 1H), 7.13–7.07 (m, 1H), 6.45 (dd, J=8.8, 8.32–8.23 (m, 1H), 7.68 (ddd, J=7.4, 1.7, 0.7Hz, 1H), 7.65–7.59
0.6Hz, 1H), 4.30–4.15 (m, 4H), 2.16 (dq, J=11.6, 5.9Hz, 2H). (m, 2H), 7.19 (dd, J=7.4, 4.8Hz, 1H), 7.12 (dd, J=12.7, 8.2Hz,
13C-NMR (100MHz, DMSO-d6) δ: 162.63, 158.98, 151.42, 1H), 4.24–4.16 (m, 4H), 2.38 (s, 3H), 2.16 (dd, J=5.7, 3.3Hz,
147.68, 146.11, 138.75, 137.17, 131.25, 125.53, 122.77, 121.17, 2H). 13C-NMR (100MHz, DMSO-d6) δ: 160.74, 156.70,
117.79, 70.87, 70.83, 31.35. MS (ESI): m/z 289.2 [M+H]+. Anal. 151.47, 151.33, 146.54, 145.49, 139.47, 137.33, 132.28, 125.41,