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

HRID 15415

반응식

HRID 15415 반응식
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

참가 물질

6

반응물 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-one2회

생성물 1

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

시약·촉매·용매 2

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

반응 조건

온도
95 °C

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-52c4e329b1004a47aec33b8bcaea8407
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07732603B2

연결된 노트

불러오는 중…