Novel diether compounds inhibiting differentiation of osteoclasts
distilled water, and saturated in NaCl aqueous solution. It
was dried over MgSO4 and the solvent was removed by
concentration under reduced pressure. Recrystallization in
ethanol was done to yield compound 2a (0.014 g, 24 %).
White powder, mp 73–74 °C; 1H NMR (400 MHz,
acetone-d6) d 7.60 (d, J = 7.9, 1H), 7.40–7.32 (m, 2H),
7.28–7.24 (m, 2H), 7.20 (t, J = 7.5, 1H), 6.92–6.88 (m,
3H), 4.05 (t, J = 7.2, 2H), 4.00 (t, J = 6.4, 2H), 1.88-1.80
(m, 4H), 1.62-1.57 (m, 2H); 13C NMR (400 MHz, DMSO-
d6, d, ppm): d 168.64, 158.57, 136.86, 129.41 (92), 126.62,
123.04, 122.88, 121.45, 120.34, 114.37 (92), 111.40,
67.06, 42.08, 28.27, 26.87, 22.75; HR-FABMS Calcd for
C18H20NO2S (M??H): 314.1215, Found: 314.1219.
0.24 mmol) was added to a solution of 4-hydroxy-N, N-
diisopropyl-3-methoxybenzamide (0.041 g, 0.16 mmol) in
6 mL of DMF and stirred at 50–55 °C for 30 min. Com-
pound 1 (0.041 g, 0.16 mmol) was added to the reaction
mixture in 3 mL of DMF and reacted at 80–90 °C for 4 h.
The reaction mixture was cooled to room temperature,
diluted with 6 mL of EtOAc and washed with distilled
water and a saturated NaCl aqueous solution. It was dried
over MgSO4 and the solvent was removed by concentration
under reduced pressure. Recrystallization in ethanol was
done to afford compound 2c (0.069 g, 91 %).
1
Yellow oil; H NMR (400 MHz, acetone-d6) d 7.60 (d,
J = 7.9, 1H), 7.40–7.31 (m, 2H), 7.20 (t, J = 7.4, 1H),
6.94 (d, J = 8.0, 1H), 6.88 (s, 1H), 6.82 (d, J = 8.0, 1H),
4.07–4.01 (m, 4H), 3.80 (s, 3H), 3.74 (brs, 2H), 1.89–1.83
(m, 4H), 1.63–1.59 (m, 2H), 1.32 (brs, 12H); 13C NMR
(400 MHz, acetone, d, ppm): d 169.88, 168.69, 149.45,
149.06, 137.36, 132.21, 126.47, 122.90, 122.64, 122.17,
118.22, 112.82, 111.06, 110.24, 68.44, 55.34 (93), 42.29,
27.15 (92), 23.14, 20.09 (94); HR-FABMS Calcd for
C26H35N2O4S (M??H): 471.2318, Found: 471.2321.
Synthesis of 4-(5-(Benzo[d]thiazol-2-yloxy)pentyloxy)ben-
zonitrile (2b) 4-Cyanophenol (0.047 g, 0.39 mmol),
NaOH (0.024 g, 0.59 mmol), and compound 1 (0.1 g,
0.39 mmol) were reacted in the same manner as compound
2a, followed by recrystallization in ethanol to yield com-
pound 2b (0.070 g, 53 %).
White powder, mp 98–101 °C; 1H NMR (400 MHz, ace-
tone-d6) d 7.68 (d, J = 9.2, 2H), 7.60 (d, J = 7.7, 1H),
7.40–7.31 (m, 2H), 7.20 (t, J = 7.5, 1H), 7.09 (d, J = 9.2,
2H), 4.13(t, J = 6.6,2H), 4.05(t, J = 7.2,2H), 1.91–1.83(m,
4H), 1.63-1.55 (m, 2H); 13C NMR (400 MHz, DMSO-d6, d,
ppm): d 168.60, 162.07. 136.83. 134.13 (92), 126.59, 123.02,
122.88, 122.84, 121.44, 115.49, 111.39 (92), 102.60, 67.85,
42.04, 27.96, 23.23, 22.57; HR-FABMS Calcd for C19H19-
N2O2S (M??H): 339.1167, Found: 339.1162.
Synthesis of 4-(5-(Benzo[d]thiazol-2-yloxy)pentyloxy)-N,N-
diethyl-3-methoxybenzamide (2d) Vanillic acid diethy-
lamide (0.044 g, 0.20 mmol), NaOH (0.012 g, 0.29 mmol),
and compound 1 (0.05 g, 0.20 mmol) were reacted in the
same manner as compound 2a, to afford compound 2d
(0.083 g, 95 %).
1
Yellow oil; H NMR (400 MHz, acetone-d6) 7.60 (d,
J = 7.7, 1H), 7.40–7.32 (m, 2H), 7.20 (t, J = 7.5, 1H),
6.97–6.95 (m, 2H), 6.90 (d, J = 8.0, 1H), 4.07–4.02 (m,
4H), 3.81 (s, 3H), 3.40–3.39 (m, 4H), 1.89–1.84 (m, 4H),
1.63–1.61 (m, 2H), 1.15 (t, J = 7.2, 6H); 13C NMR
(400 MHz, acetone, d, ppm): d 171.04, 169.68, 150.46,
150.30, 138.32, 131.30, 127.45, 123.89, 123.63, 123.60,
123.15, 120.15, 113.55, 112.04, 69.40, 56.38 (92), 43.26,
43.08, 28.14, 24.51, 24.10, 14.01 (92); HR-FABMS Calcd
for C24H31N2O4S (M??H): 443.2005, Found: 443.2008.
Synthesis of 4-(5-(Benzo[d]thiazol-2-yloxy)pentyloxy)-N,N-
diisopropyl-3-methoxybenzamide (2c) Synthesis of 4-Hy-
droxy-N, N-diisopropyl-3-methoxybenzamide. A solution of
4-hydroxy-3-methoxybenzoic acid (0.1 g, 0.59 mmol) in
5 mL of dichloromethane was mixed with SOCl2 (0.637 g,
5.35 mmol) and 0.025 mL of DMF in that order and
refluxed for 1 h. Following concentration under reduced
pressure using a rotary evaporator, the residue was dis-
solved in 5 mL of dichloromethane, and then mixed with
diisopropylamine (0.301 g, 2.97 mmol) in an ice bath. The
mixture was stirred at room temperature for 2 h, diluted
with 5 mL of EtOAc and washed with 1 N HCl aqueous
solution, 1 N NaOH aqueous solution and a saturated NaCl
aqueous solution. It was dried over MgSO4 and the solvent
was removed by concentration under reduced pressure to
afford 4-hydroxy-N, N-diisopropyl-3-methoxybenzamide
(0.087 g, 58 %).
Synthesis of 2-(5-(3,5-dimethylphenoxy)pentyloxy)benzo[d]
thiazole (2e) 3,5-Dimethylphenol (0.40 g, 0.33 mmol),
NaOH (0.020 g, 0.50 mmol), and compound 1 (0.085 g,
0.33 mmol) were reacted for 4 h in the same manner as
compound 2a, and recrystallization in ethanol was done to
afforded compound 2e (0.108 g, 96 %).
White powder, mp 61–63 °C; 1H NMR (400 MHz,
acetone-d6) d 7.59 (d, J = 7.7, 1H), 7.39–7.31 (m, 2H),
7.20 (t, J = 7.5, 1H), 6.54 (s, 1H), 6.52 (s, 2H), 4.04 (t,
J = 7.4, 2H), 3.94 (t, J = 6.4, 2H), 2.22 (s, 6H), 1.84–1.78
(m, 4H), 1.59–1.54 (m, 2H); 13C NMR (400 MHz, DMSO-
d6, d, ppm): d 168.63, 158.62, 138.47 (92), 136.86, 126.60,
123.03, 122.86 (92), 121.96, 121.46, 112.11, 111.38,
66.91, 42.09, 28.32, 26.85, 22.75, 21.01 (92); HR-FABMS
Pale yellow powder; 1H NMR (400 MHz, acetone-d6) d
7.27 (d, J = 8.0, 1H), 7.07 (s, 1H), 6.92 (d, J = 8.2, 1H),
3.88 (s, 3H), 3.73 (brs, 2H), 1.32 (brs, 12H).
Synthesis of 4-(5-(Benzo[d]thiazol-2-yloxy)pentyloxy)-N,N-
diisopropyl-3-methoxybenzamide (2c) NaOH (0.010 g,
123