6-Aminophthalide → 2-(3-Oxo-1,3-dihydroisobenzofuran-5-ylamino)-6-(3-acetamidophenyl)pyrazine

HRID 16264

反応式

HRID 16264 の反応式
[C:1]([NH:4][C:5]1[CH:6]=[C:7]([C:11]2[CH:16]=[N:15][CH:14]=[C:13](Cl)[N:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:3])[CH3:2].[NH2:18][C:19]1[CH:27]=[C:26]2[C:22]([CH2:23][O:24][C:25]2=[O:28])=[CH:21][CH:20]=1.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1>[O:28]=[C:25]1[C:26]2[C:22](=[CH:21][CH:20]=[C:19]([NH:18][C:13]3[N:12]=[C:11]([C:7]4[CH:6]=[C:5]([NH:4][C:1](=[O:3])[CH3:2])[CH:10]=[CH:9][CH:8]=4)[CH:16]=[N:15][CH:14]=3)[CH:27]=2)[CH2:23][O:24]1

参加物

6

反応物 4

HCID 936316-AminophthalideHCID 634876Binap, (A+-)-HCID 116874302-(3-Acetamidophenyl)-6-chloropyrazineHCID 23676156Sodium t-butoxide

生成物 1

HCID 117174492-(3-Oxo-1,3-dihydroisobenzofuran-5-ylamino)-6-(3-acetamidophenyl)pyrazine収率 26.2%

試薬・触媒・溶媒 1

HCID 1140Toluene溶媒

実験手順

Using Method L, 2-(3-acetamidophenyl)-6-chloropyrazine (4a) (60 mg, 0.24 mmol), 6-amino-1,3-dihydroisobenzofuran-1-one (52.2 mg, 0.35 mmol), Pd(0)2 dba3 (9 mg, 0.01 mmol), BINAP (50 mg, 0.04 mmol), sodium tert-butoxide (33 mg, 0.34 mmol) and toluene (5 mL) were reacted at 85° C. for 16 hours. The same workup as for Method L was followed by washing of the resulting solid with dichloromethane (30 mL) and filtration. The insoluble solid was then washed with acetone (60 mL). The acetone was evaporated under vacuo and the resulting solid was crystallised in cold dimethylformamide: dichloromethane mixtures to give 22.7 mg of title compound. Yield: 26.2%. 1 H NMR (250 MHz, DMSO-d6) δ 2.09 (s, 3 H), 5.39 (s, 2 H), 7.45 (t, 1 H, 8.0 Hz), 7.62-7.69 (m, 2 H), 7.76 (d, 1 H, 7.9 Hz), 8.23 (s, 1 H), 8.24-8.29 (m, 2 H), 8.39 (bs, 1 H), 8.50 (s, 1 H), 9.99 (s, 1 H), 10.06 (s, 1 H); 13C NMR (62.9 MHZ, DMSO-d6) δ 24.05, 69.78, 112.78, 117.31, 120.16, 121.13, 123.36, 124.58, 125.59, 129.29, 130.73, 133.63, 136.83, 139.71, 139.94, 141.47, 147.88, 151.05, 168.47, 170.75; m/z 361.2 [(M+H)+, calcd for C20H16N4O3 360.1].

後処理

  1. customwere reacted at 85° C. for 16 hours
  2. washby washing of the resulting solid with dichloromethane (30 mL) and filtration
  3. washThe insoluble solid was then washed with acetone (60 mL)
  4. customThe acetone was evaporated under vacuo
  5. customthe resulting solid was crystallised in cold dimethylformamide

出典と根拠

ORDレコード
ord-9965f525139e497fb74803905eebc58c
出典データセット
uspto-grants-2010_06
特許番号
US07737152B2

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