1(2H)-PyriMidinehexanoic acid, 4-[1,1'-biphenyl]-4-yl-3,4-dihydro-6-Methyl-2-oxo-5-[(phenylMethoxy)carbonyl]- synthesis

Yield:831217-43-7 50%

Reaction Conditions:

with hydrogenchloride in tetrahydrofuran;water at 20; for 20 h;

Steps:

9 4.1.9. Benzyl 4-([1,10-biphenyl]-4-yl)-6-methyl-1-(6-(methylsulfonamido)-6-oxohexyl)-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate (ML282-66)

A suspension of 6-ureidohexanoic acid (1.00 g, 5.74 mmol) and 4-biphenylcarboxaldehyde (1.58 g, 8.61 mmol, 1.5 equiv) in THF (10 mL) at rt was treated with benzyl acetoacetate (1.53 mL, 8.61 mmol, 1.5 equiv), followed by addition of concd HCl (1 drop).
The suspension was stirred at rt for 20 h, and concentrated in vacuo to give a yellow oil that was suspended several times in hexanes over 3 h to obtain a yellow solid.
The yellow solid was collected by filtration, then dissolved in hot EtOAc and precipitated with hexanes.
The precipitate was collected by filtration and dried in vacuo to give 6-(4-([1,1'-biphenyl]-4-yl)-5-((benzyloxy)carbonyl)-6-methyl-2-oxo-3,4-dihydropyrimidin-1(2H)-yl)hexanoic acid (1.48 g, 2.89 mmol, 50%) as a light yellow solid that was used without further purification: ¹H NMR (400 MHz, CDCl₃) δ 7.55 (d, 2H, J = 8.0 Hz), 7.48 (d, 2H, J = 8.0 Hz), 7.43 (t, 2H, J = 8.0 Hz), 7.34 (t, 1H, J = 7.2 Hz), 7.29-7.23 (m, 5H), 7.17-7.15 (m, 2H), 5.98 (d, 1H, J = 2.4 Hz), 5.42 (d, 1H, J = 2.1 Hz), 5.12, 5.08 (ABq, 1H, J = 12.4 Hz), 3.94-3.86 (m, 1H), 3.64-3.57 (m, 1H), 2.54 (s, 3H), 2.30 (t, 2H, J = 5.4 Hz), 1.70-1.51 (m, 4H), 1.35-1.24 (m, 2H).

References:

Ireland, Alex W.;Gobillot, Theodore A.;Gupta, Tushar;Seguin, Sandlin P.;Liang, Mary;Resnick, Lynn;Goldberg, Margot T.;Manos-Turvey, Alexandra;Pipas, James M.;Wipf, Peter;Brodsky, Jeffrey L. [Bioorganic and Medicinal Chemistry,2014,vol. 22,# 22,p. 6490 - 6502]