Organic & Biomolecular Chemistry
Paper
4.04 (dd, J = 11.5/4.2 Hz, 2H, CH2equat.–O–CH2equat.), 7.29 (d, J = 2-[4-(Acetamido)phenyl]-N-{4-[N-methyl-N-(tetrahydro-2H-
8.1 Hz, 1H, 4-CH), 7.32 (d, J = 8.6 Hz, 2H, 3-Hphenyl, 5-Hphenyl), pyran-4-yl)aminomethyl]phenyl}-6,7-dihydro-5H-benzo[7]-
7.43 (s, 1H, 9-CH), 7.50 (dd, J = 7.8/1.9 Hz, 1H, 3-CH), annulene-8-carboxamide (2e)
7.53–7.59 (m, 3H, 1-CH, 2-Hphenyl, 6-Hphenyl), 7.64 (s, 1H, N–H),
7.75 (d, J = 8.3 Hz, 2H, 2-Hformylphen, 6-Hformylphen.), 7.96 (d, J =
As described for 2a, amide 3 (100 mg, 0.21 mmol), PdCl2(dppf)
(8 mg, 0.01 mmol, 5 mol%), KOAc (14 mg, 0.42 mmol, 2 eq.)
and 4-acetamidophenylboronic acid (43 mg, 0.24 mmol, 1.1
eq.) in dry dimethoxyethane (5 mL) were heated to reflux for
8.3 Hz, 2H, 3-Hformylphen, 5-Hformylphen), 10.06 (s, 1H, CHvO).
13C NMR (CDCl3): δ (ppm) = 28.3 (C-6), 29.7 (C-3pyran, C-5pyran),
30.1 (C-7), 35.1 (C-5), 38.0 (N–CH3), 57.7 (Ph–CH2–N), 60.0
12 h. Purification by fc (EtOAc–MeOH = 95 : 5, ∅ = 2 cm, l =
(C-4pyran), 68.2 (C-2pyran, C-6pyran), 120.5 (C-2phenyl, C-6phenyl),
6 cm, V = 30 mL) afforded a pale yellow oil, which was recrys-
127.6 (C-3), 127.9 (C-3formylphen., C-5formylphen), 129.9 (C-3phenyl
,
tallized from acetonitrile to give the amide 2e as a colorless
solid. Rf = 0.10 (CH2Cl2–MeOH = 95 : 5), mp 164–166 °C, yield
88 mg (78%). C33H37N3O3 (523.6 g mol−1). Purity (HPLC): 99%,
tR = 18.41 min. Exact MS (APCI): m/z = calcd for C33H38N3O3
C-5phenyl), 130.6 (C-4), 130.8 (C-2formylphen., C-6formylphen), 131.4
(C-1), 134.3 (C-9), 135.5 (C-9a), 135.6 (C-4phenyl), 138.2 (C-2),
138.9 (C-8), 140.7 (C-1phenyl), 143.3 (C-4formylphen), 146.9
(C-1formylphen), 168.2 (OvC–NH), 192.3 (CHvO). The signal for
the carbon atom C-4a is not visible. FT-IR (neat): ˜ν (cm−1) =
3305 (N–H), 2966, 2947 (C–Halkyl), 1697 (HCvO), 1647 (CvO),
1099, 1010, (C–O).
1
[MH+] 524.2908, found 524.2919. H NMR (CDCl3): δ (ppm) =
1.57–1.79 (m, 4H, 3-CH2pyran, 5-CH2pyran), 2.12–2.20 (m, 2H,
6-CH2), 2.21 (s, 6H, N–CH3, COCH3), 2.56–2.70 (m, 1H,
4-CHpyran) 2.72 (t, J = 6.7 Hz, 2H, 7-CH2), 2.83–2.94 (m, 2H,
5-CH2), 3.37 (td, J = 11.6/2.3 Hz, 2H, CH2axial–O–CH2axial), 3.57
(s, 2H, Ph–CH2–N), 4.04 (dd, J = 11.4/4.2 Hz, 2H, CH2equat.–O–
CH2equat.), 7.23 (d, J = 7.8 Hz, 1H, 4-CH), 7.31 (d, J = 8.5 Hz,
3H, 3-Hphenyl, 5-Hphenyl, N–Hacetamidophenyl), 7.38–7.44 (m, 2H,
9-CH, 3-CH), 7.48 (d, J = 2.0 Hz, 1H, 1-CH), 7.51–7.62 (m, 6H,
2-Hphenyl, 6-Hphenyl, 2-, 3-, 5-, 6-Hacetamidophenyl), 7.66 (s, 1H,
N–H). 13C NMR (CDCl3): δ (ppm) = 25.1 (COCH3), 28.4 (C-6),
29.7 (C-3pyran, C-5pyran), 30.9 (C-7), 35.0 (C-5), 38.0 (N–CH3),
57.7 (Ph–CH2–N), 60.0 (C-4pyran), 68.2 (C-2pyran, C-6pyran), 120.5
(C-2phenyl, C-6phenyl), 120.6 (C-3acetamidophenyl, C-5acetamidophenyl.),
127.2 (C-3), 127.9 (C-2acetamidophenyl, C-6acetamidophenyl), 129.9
(C-3phenyl, C-5phenyl), 130.4 (C-4), 130.9 (C-1), 134.7 (C-9), 135.2
C-9a), 137.3 (C-1acetamidophenyl), 137.7 (C-4phenyl), 138.5 (C-2),
138.9 (C-8), 141.9 (C-1phenyl), 146.3 (1C, C-4acetamidophen), 168.5
(OvC–NH), 170.4 (COCH3). The signal for the quaternary
carbon atom C-4a is not visible. FT-IR (neat): ˜ν (cm−1) = 3305
(N–H), 2947, 2920 (C–Halkyl), 1670, 1697 (CvO), 1111, 1010,
(C–O).
Methyl 4-[8-(N-{4-[N-methyl-N-(tetrahydro-2H-pyran-4-yl)-
aminomethyl]phenyl}carbamoyl)-6,7-dihydro-5H-benzo[7]-
annulen-2-yl]benzoate (2d)
As described for 2a, amide 3 (100 mg, 0.21 mmol), PdCl2(dppf)
(8 mg, 0.01 mmol, 5 mol%), KOAc (14 mg, 0.42 mmol, 2 eq.)
and 4-methoxycarbonylphenylboronic acid (43 mg, 0.23 mmol,
1.1 eq.) in dry dimethoxyethane (5 mL) were heated to reflux
for 12 h. Purification by fc (EtOAc–MeOH = 95 : 5, ∅ = 2 cm, l =
8 cm, V = 10 mL) afforded a colorless oil, which was recrystal-
lized from acetonitrile to give the amide 2d as a colorless
solid. Rf = 0.17 (CH2Cl2–MeOH = 95 : 5), mp 191 °C, yield
82 mg (73%). C33H36N2O4 (524.6 g mol−1). Purity (HPLC):
>97%, tR = 22.19 min. Exact MS (APCI): m/z = calcd for
C33H37N2O4 [MH+] 525.2748, found 525.2776. 1H NMR
(CDCl3): δ (ppm) = 1.59–1.79 (m, 4H, 3-CH2pyran, 5-CH2pyran),
2.08–2.21 (m, 2H, 6-CH2), 2.21 (s, 3H, N–CH3), 2.64 (tt, J = 11.0/
3.8 Hz, 1H, 4-CHpyran) 2.73 (t, J = 6.6 Hz, 2H, 7-CH2), 2.85–2.97
(m, 2H, 5-CH2), 3.37 (td, J = 12.0/1.8 Hz, 2H, CH2axial–O–
CH2axial), 3.57 (s, 2H, Ph–CH2-N), 3.94 (s, 3H, CO2CH3), 4.04
(dd, J = 11.0/4.0 Hz, 2H, CH2equat.–O–CH2equat.), 7.27 (d, J =
2-[4-(Dimethylamino)phenyl]-N-{4-[N-methyl-N-(tetrahydro-2H-
pyran-4-yl)aminomethyl]phenyl}-6,7-dihydro-5H-benzo[7]-
annulene-8-carboxamide (2f)
8.9 Hz, 1H, 4-CH), 7.31 (d, J = 7.4 Hz, 2H, 3-Hphenyl, 5-Hphenyl), As described for 2a, amide 3 (200 mg, 0.42 mmol), PdCl2(dppf)
7.42 (s, 1H, 9-CH), 7.49 (dd, J = 7.9/1.6 Hz, 1H, 3-CH), (16 mg, 0.02 mmol, 5 mol%), KOAc (84 mg, 0.84 mmol, 2 eq.)
7.50–7.60 (m, 3H, 1-CH, 2-Hphenyl, 6-Hphenyl), 7.62 (s, 1H, N–H), and
4-(dimethylamino)phenylboronic
acid
(106
mg,
7.65 (d, J = 8.5 Hz, 2H, 2-Hmethylbenzoate, 6-Hmethylbenzoate), 8.11 0.63 mmol, 1.5 eq.) in dimethoxyethane (10 mL) were heated
(d, J = 8.4 Hz, 2H, 3-Hmethylbenzoate., 5-Hmethylbenzoate). 13C NMR to reflux for 12 h. Purification by fc (EtOAc–CH2Cl2 + 5%
(CDCl3): δ (ppm) = 28.3 (C-6), 29.6 (C-3pyran, C-5pyran), 30.9 MeOH = 1 : 2, ∅ = 3 cm, l = 8 cm, V = 30 mL) afforded a pale
(C-7), 35.1 (C-5), 38.0 (N–CH3), 52.6 (CO2CH3), 57.7 (Ph–CH2– yellow solid, which was recrystallized from acetonitrile to give
N), 60.0 (C-4pyran), 68.2 (C-2pyran, C-6pyran), 120.5 (C-2phenyl
,
the amide 2f as a colorless solid. Rf = 0.19 (CH2Cl2–MeOH =
C-6phenyl), 127.2 (C-3methylbenzoate., C-5methylbenzoate.), 127.6 (C-3), 95 : 5), mp 174–176 °C, yield 202 mg (93%). C33H39N3O2
129.4 (C-1methylbenzoate.), 129.9 (C-3phenyl, C-5phenyl), 130.5 (C-4), (509.7 g mol−1). Purity (HPLC): 99%, tR = 18.43 min. Exact MS
130.6 (C-2methylbenzoate, C-6methylbenzoate), 131.4 (C-1), 134.3 (ESI): m/z = calcd for C33H40N3O2 [MH+] 510.3115, found
(C-9), 134.4 (C-9a), 135.4 (C-4a), 137.2 (C-4phenyl), 138.5 (C-2), 510.21. 1H NMR (CDCl3): δ (ppm) = 1.61–1.80 (m, 4H,
138.9 (C-8), 142.9 (C-1phenyl), 145.3 (C-4methylbenzoate), 167.4 3-CH2pyran, 5-CH2pyran), 2.10–2.21 (m, 2H, 6-CH2), 2.21 (s, 3H,
(CO2CH3), 168.4 (OvC–NH). FT-IR (neat): ˜ν (cm−1) = 3286 N–CH3), 2.64 (tt, J = 11.4/4.2 Hz, 1H, 4-CHpyran) 2.71 (t, J = 6.0 Hz,
(N–H), 2951, 2920 (C–Halkyl), 1701 (CvOester), 1647 (CvO), 2H, 7-CH2), 2.82–2.92 (m, 2H, 5-CH2), 3.00 (s, 6H, N(CH3)2),
1076, 1014, (C–O).
3.37 (td, J = 11.6/2.4 Hz, 2H, CH2axial–O–CH2axial), 3.57 (s, 2H,
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Org. Biomol. Chem., 2014, 12, 177–186 | 183