Synthesis of 1-(3-chlorophenethyl)-3-cyclopentylpyrimidine-2,4,6-(1H,3H,5H)-trione (CP8)
Stephanie J Cragg, Katherine Brimblecombe, Carole JR Bataille
calcium channel antagonist
1-(3-chlorophenethyl)-3-cyclopentylpyrimidine-2
4
6-(1H
3H
5H)-trione (8)
synthesis
Abstract
A structure-activity relationship-based modification of pyrimidine-2,4,6-triones led to 1-(3-chlorophenethyl)-3-cyclopentylpyrimidine-2,4,6-(1 H ,3 H ,5 H )-trione (CP8), a potent and highly selective CaV1.3 L-type calcium channel antagonist. This protocol is an adaption of Kang, S., Cooper, G., Dunne, S. et al., 2012's method of the synthesis of this chemical.
Steps
Synthesis of 1-(3-chlorophenethyl)-3-cyclopentylpyrimidine-2,4,6-(1H,3H,5H)-trione (CP8)
Add 357 µL 2-(3-chlorophenyl)ethylamine (2.58 mmol, 1.0 eq.) to a solution of 290 mg of Cyclopentaneisocyanate (2.58 mmol, 1.0 eq.) in 10 mL of dichloromethane.
Stir at RT for 5 h.
Monitor completion with Low-Resolution Mass Spectrometry.
Add 276 µL Malonyl chloride (2.84 mmol, 1.1 eq.) dropwise under vigorous stirring over 5 min.
Stir mixture for 1 h and concentrate in vacuo.
Purify residue by column chromatography on silica gel (EtOAc/pentane, 1:4), product should be a white solid (687 mg, 80%)
Nuclear Magnetic Resonance (NMR) Spectroscopy
Check data from NMR spectroscopy is comparable with the literature (Kang, S., Cooper, G., Dunne, S. et al., 2012):
1H NMR (400 MHz, CDCl3) δ 7.25 – 7.19 (m, 3H), 7.13 (dt, J = 6.7, 2.1 Hz, 1H), 5.20 – 5.07 (m, 1H), 4.13 – 4.03 (m, 2H), 3.62 (s, 2H), 2.92 – 2.84 (m, 2H), 1.94 (tqd, J = 8.0, 4.9, 2.0 Hz, 4H), 1.89 – 1.79 (m, 2H), 1.61 – 1.57 (m, 2H)
13C NMR (101 MHz, CDCl3) δ 164.9, 164.6, 151.1, 140.0, 134.5, 123.0, 129.2, 127.3, 127.1, 54.6, 42.8, 40.3, 33.8, 28.8, 25.7; LRMS m/z (ESI¯) 333.1 [M-H]¯
