반응 #43693

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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

용매

DMF

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후처리

1. 1
   기타The reaction mixture is degassed
2. 2
   기타purged with nitrogen
3. 3
   기타The reaction mixture is partitioned between water and EtOAc
4. 4
   세척The combined organic phases are washed with brine
5. 5
   건조dried (anhydrous sodium sulfate)
6. 6
   농축concentrated
7. 7
   세척eluting with EtOAc: MeOH:NH4OH (90:10:1)

실험 절차

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.

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