synthesis and in vitro pharmacology of a series of histamine h2 ...

Chapter 7
N-benzoyl-N'-{cth[3,5-diethoxycarbonyl-l ,4-dihydro-6-methyl~4-(substitutedphenyl)-pyridin-2~yl]methylthio}alkylthiourea
Under nitrogen atmosphere at 0°C 20 mmol benzoyl isothiocyanate in 150 ml
dichloromethane was added dropwise to a solution of 20 mmol diethyl 2-(coaminoalkyl)thiomethyl-6-methyl-4-(substituted-phenyl)-1,4-dihydropyridine-3,5-dicarboxylate
in 150 ml dichloromethane. Stirring was continued for 2 hours while the
temperature was raised until room temperature. The reaction mixture was evaporated
and the residue was washed four times with 50 ml diethyl ether.
N-benzoyl-N'-{2-[(3J-diethoxycarbonyl-l ,4-dihydro-6-methyl-4-phenylpyridin-2yl)methylthio]
ethyl} thiourea
Yield = 82%; melting point = 52.8-54.1 °C.
The product was purified by column chromatography, using petroleum ether 60-
80°C/ethyl acetate 3:2 as eluent (R f = 0.5).
^-NMR (CDC1 3): 1.15-1.28 ppm (m, 6H, 2x C// 3-CH 2-0), 2.39 ppm (s, 3H, pyridine-
C// 3), 2.79-2.88 ppm (m, 2H, S-C// 2-C-N), 3.89-3.96 ppm (m, 2H, S-C-C// 2-N), 4.02-
4.18 ppm (m, 6H, pyridine-C// 2-S and 2x CH 3-C// 2-0), 5.02 ppm (s, 1H, pyridine-// 4),
6.74 ppm (s, 1H, pyridine-N//), 7.10-7.90 ppm (m, 10H, 5x benzoyl-// and 5x phenyl-
//), 9.03 ppm (bs, 1H, -C(S)-N//-C(0)-), 11.01 ppm (bs, 1H, S-C-C-N//-).
N-benzoyl-N'-{2-{[4-(2J-dichlorophenyl)-3,5-diethoxycarbonyl-l ,4-dihydro-6methylpyridin-2-y
I] methylthio} ethyl} thiourea
Yield = 65 %; melting point = 54.5-55.6 °C.
The product was purified by column chromatography, using petroleum ether 60-
80°C/ethyl acetate 2:1 as eluent (R f = 0.5).
*H-NMR (CDC1 3): 1.14-1.29 ppm (m, 6H, 2x C// 3-CH 2-0), 2.37 ppm (s, 3H, pyridine-
C// 3), 2.88 ppm (t, / = 6.7 Hz, 2H, S-C// 2-C-N), 3.91-4.15 ppm (m, 8H, S-C-C// 2-N and
pyridine-C// 2-S and 2x CH 3-C// 2-0), 5.51 ppm (s, 1H, pyridine-// 4), 6.81 ppm (s, 1H,
pyridine-N//), 7.06-7.08 ppm (m, 1H, phenyl-//), 7.22-8.08 ppm (m, 7H, 5x benzoyl-//
and 2x phenyl-//), 9.06 ppm (bs, 1H, -C(S)-N//-C(0)-), 11.03 ppm (bs, 1H, S-C-C-N//-).
N-benzoyl-N'-{2-{[3£-diethoxycarbonyl-l ,4-dihydro-6>-methyl-4-(3-nitrophenyl)pyridin-2-yl]methylthio}ethyl}thiourea
Yield = 91%; melting point = 56.0-57.8 °C.
The product was purified by column chromatography, using petroleum ether 60-
80°C/ethyl acetate 2:1 as eluent (Rf = 0.3; diethyl ether as eluent).
!
H-NMR (CDC13): 1.17-1.30 ppm (m, 6H, 2x C// 3-CH2-0), 2.40 ppm (s, 3H, pyridine-
C// 3), 2.87 ppm (t, J = 7.3 Hz, 2H, S-C// 2-C-N), 3.85-4.22 ppm (m, 8H, S-C-C// 2-N and
pyridine-C// 2-S and 2x CH3-C// 2-0), 5.10 ppm (s, 1H, pyridine-// 4), 7.03 ppm (s, 1H,
pyridine-N//), 7.28-7.81 ppm (m, 7H, 5x benzoyl-// and 2x phenyl-//), 8.00-8.03 ppm
(m, 1H, phenyl-//), 8.10 ppm (bs, 1H, phenyl-// 2), 9.04 ppm (bs, 1H, -C(S)-N//-C(0)-),
11.03 ppm (bs, 1H, S-C-C-N//-).
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