Potassium Phosphate, Tribasic → 5-(4'-Chlorobiphenyl-4-yl)-7-(4-methoxy-benzyl)-7,8-dihydro-imidazo[1,5-a]pyrazin-6-one

HRID 15415

反応式

HRID 15415 の反応式
Br[C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[N:13]3[CH:14]=[N:15][CH:16]=[C:12]3[CH2:11][N:10]([CH2:17][C:18]3[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=3)[C:9]2=[O:26])=[CH:4][CH:3]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[Cl:35][C:36]1[CH:41]=[CH:40][C:39](B(O)O)=[CH:38][CH:37]=1>CN(C=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Cl:35][C:36]1[CH:41]=[CH:40][C:39]([C:2]2[CH:7]=[CH:6][C:5]([CH:8]3[N:13]4[CH:14]=[N:15][CH:16]=[C:12]4[CH2:11][N:10]([CH2:17][C:18]4[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=4)[C:9]3=[O:26])=[CH:4][CH:3]=2)=[CH:38][CH:37]=1

参加物

6

反応物 3

HCID 62657Potassium Phosphate, TribasicHCID 742994-Chlorophenylboronic acidHCID 100472795-(4-Bromo-phenyl)-7-(4-methoxy-benzyl)-7,8-dihydro-imidazo[1,5-a]pyrazin-6-one2 回

生成物 1

HCID 100721285-(4'-Chlorobiphenyl-4-yl)-7-(4-methoxy-benzyl)-7,8-dihydro-imidazo[1,5-a]pyrazin-6-one

試薬・触媒・溶媒 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 6228Dimethylformamide溶媒

反応条件

温度
95 °C

実験手順

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.

後処理

  1. customThe reaction mixture is degassed
  2. custompurged with nitrogen
  3. customThe reaction mixture is partitioned between water and EtOAc
  4. washThe combined organic phases are washed with brine
  5. dry with materialdried (anhydrous sodium sulfate)
  6. concentrationconcentrated
  7. washeluting with EtOAc: MeOH:NH4OH (90:10:1)

出典と根拠

ORDレコード
ord-52c4e329b1004a47aec33b8bcaea8407
出典データセット
uspto-grants-2010_06
特許番号
US07732603B2

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