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

HRID 16264

Reaction equation

HRID 16264 reaction equation
[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

Participants

6

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

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].

Workup

  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

Sources & evidence

ORD record
ord-9965f525139e497fb74803905eebc58c
Source dataset
uspto-grants-2010_06
Patent number
US07737152B2

Linked notes

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