Reaction #43693

Reaction equation

title compound

5-(4-Bromo-phenyl)-7-(4-methoxy-benzyl)-7,8-dihydro-imidazo[1,5-a]pyrazin-6-one

5-(4-bromo-phenyl)-7-(4-methoxy-benzyl)-7,8-dihydro-imidazo[1,5-a]pyrazin-6-one

potassium phosphate

4-chlorophenyl boronic acid

→

5-(4′-chlorobiphenyl-4-yl)-7-(4-methoxy-benzyl)-7,8-dihydro-imidazo[1,5-a]pyrazin-6-one

Solvents

DMF

Conditions

Workup

1. 1
   OtherThe reaction mixture is degassed
2. 2
   Otherpurged with nitrogen
3. 3
   OtherThe reaction mixture is partitioned between water and EtOAc
4. 4
   WashThe combined organic phases are washed with brine
5. 5
   Dryingdried (anhydrous sodium sulfate)
6. 6
   Concentrationconcentrated
7. 7
   Washeluting with EtOAc: MeOH:NH4OH (90:10:1)

Procedure

To a solution of the title compound of Example 21, 5-(4-bromo-phenyl)-7-(4-methoxy-benzyl)-7,8-dihydro-imidazo[1,5-a]pyrazin-6-one (0.125 g, 0.30 mmol) in DMF (2 mL) is added potassium phosphate (0.129 g, 0.61 mmol) and 4-chlorophenyl boronic acid (0.057 g, 0.36 mmol) followed by [1,1′-bis(diphenylphosphino)-ferrocene]dichloropalladium (II) (0.025 g, 10 mol %). The reaction mixture is degassed, purged with nitrogen then heated at 95° C. for 5 h. The reaction mixture is partitioned between water and EtOAc. The combined organic phases are washed with brine, dried (anhydrous sodium sulfate) and concentrated. The residue is subjected to flash chromatography (silica) eluting with EtOAc: MeOH:NH4OH (90:10:1) to give 5-(4′-chlorobiphenyl-4-yl)-7-(4-methoxy-benzyl)-7,8-dihydro-imidazo[1,5-a]pyrazin-6-one which is dissolved in diethyl ether and treated with HCl(g)-MeOH and the precipitated product, 5-(4′-chlorobiphenyl-4-yl)-7-(4-methoxy-benzyl)-7,8-dihydro-imidazo[1,5-a]pyrazin-6-one hydrochloride is collected by filtration and dried: m.p. 270-273° C.; 1H-NMR (DMSO-d8) δ 9.19 (1H, s), 7.73 (5H, m), 7.54 (2H, d, J=8.3), 7.37 (2H, d, J=8.3), 7.22 (2H, d, J=8.6), 6.90 (2H, d, J=8.6), 6.49 (1H, s), 4.67 (4H, m), 3.73 (3H, s); 13C-NMR (DMSO-d6) 163.0, 158.8, 139.6, 137.9, 134.4, 133.9, 132.7, 129.4, 128.9, 128.5, 127.6, 127.4, 124.7, 115.3, 114.0, 60.8, 55.0, 48.9; e/z (ES) 444 (M+1, 100%); calculated for C26H22N3O2Cl HCl, C, 65.01; H, 4.83; N, 8.75. found C, 64.64; H, 4.78; N, 8.74.

Source