Acetonitrile--water (1/1) → HCID 67044596, compound

HRID 2261979Notes

Reaction equation

HRID 2261979 reaction equation
[Cl:1][C:2]1[C:3]([F:27])=[C:4]([N:8]2[C:16]([C:18]3[CH:23]=[CH:22][C:21]([NH2:24])=[C:20]([NH2:25])[CH:19]=3)([OH:17])[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[C:9]2=[O:26])[CH:5]=[CH:6][CH:7]=1.[CH3:28][O:29][C:30](=[O:44])[C:31]([NH:33]/[C:34](=N/C(=O)C(OC)=O)/SC)=[O:32].C(#N)C.O>C(O)CCC>[Cl:1][C:2]1[C:3]([F:27])=[C:4]([N:8]2[C:9](=[O:26])[C:10]3[C:15](=[CH:14][CH:13]=[CH:12][CH:11]=3)[C:16]2([C:18]2[CH:23]=[CH:22][C:21]3[N:24]=[C:34]([NH:33][C:31](=[O:32])[C:30]([O:29][CH3:28])=[O:44])[NH:25][C:20]=3[CH:19]=2)[OH:17])[CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 18373917Acetonitrile--water (1/1)HCID 67045347HCID 67045347, compoundHCID 178501868HCID 178501868, compound

Product 1

HCID 67044596HCID 67044596, compoundYield 38%

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Procedure

A solution of 2-(3-chloro-2-fluorophenyl)-3-(3,4-diaminophenyl)-3-hydroxy-2,3-dihydro-1H-isoindol-1-one (0.10 g, 0.26 mmol) and methyl {[(1Z)-{[(methyloxy)(oxo)acetyl]amino}(methylthio)methylidene]amino}(oxo)acetate (67 mg, 0.26 mmol) in n-butanol (2.0 mL) was heated to 80° C. for 5 hours. The reaction mixture was cooled to room temperature and the solvent was evaporated. The resulting crude product was purified by reverse phase preparative HPLC (CH3CN/25 mM aqueous ammonium acetate). The fractions were collected, and the solvent was concentrated. The aqueous residue was partitioned with ethyl acetate. The organic layer was washed with saturated aqueous sodium bicarbonate, brine and dried over anhydrous sodium sulfate. Filtration and concentration resulted in an oily residue, which was lyophillized from a mixture of acetonitrile-water (5.0 mL) to give methyl ({6-[2-(3-chloro-2-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}amino)(oxo)acetate (48 mg, 38% yield. 1H NMR (400 MHz, DMSO-d6): 11.86 (d, 1H), 7.87 (d, 1H), 7.65 (m, 2H), 7.53 (t, 1H), 7.33 (t, 1H), 7.30 (d, 1H), 7.25 (s, 1H), 7.20 (t, 1H), 6.99 (d, 1H), 6.91 (d, 1H), 3.57 (s, 3H); 13C NMR (400 MHz, DMSO-d6): 67.0, 92.5, 110.0, 113.8, 114.1, 115.7, 120.8, 121.4, 123.9, 125.3, 125.6, 126.0, 126.2, 129.5, 129.8, 130.5, 130.7, 134.3, 134.8, 150.3, 155.7, 155.8, 163.5, 166.2; MS (EI) for C24H16ClFN4O4: 436 (M-CO2CH3).

Workup

  1. customthe solvent was evaporated
  2. customThe resulting crude product was purified by reverse phase preparative HPLC (CH3CN/25 mM aqueous ammonium acetate)
  3. customThe fractions were collected
  4. concentrationthe solvent was concentrated
  5. customThe aqueous residue was partitioned with ethyl acetate
  6. washThe organic layer was washed with saturated aqueous sodium bicarbonate, brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationFiltration and concentration
  9. customresulted in an oily residue, which

Sources & evidence

ORD record
ord-145b76375fb643cea00bb11a1be0e305
Source dataset
uspto-grants-2010_12
Patent number
US07846959B2

Reaction notes

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