Water → HCID 59681773, compound

HRID 1394176Notes

Reaction equation

HRID 1394176 reaction equation
[NH2:1][C:2]1[C:3]([C:7]2[N:8]([C:16]3[CH:21]=[CH:20][C:19]([OH:22])=[CH:18][CH:17]=3)[C:9]3[CH:14]=[CH:13][N:12]=[CH:11][C:10]=3[N:15]=2)=[N:4][O:5][N:6]=1.[H-].[Na+].Cl[CH2:26][C:27]#[N:28].O>CN(C=O)C.CCOC(C)=O>[NH2:1][C:2]1[C:3]([C:7]2[N:8]([C:16]3[CH:21]=[CH:20][C:19]([O:22][CH2:26][C:27]#[N:28])=[CH:18][CH:17]=3)[C:9]3[CH:14]=[CH:13][N:12]=[CH:11][C:10]=3[N:15]=2)=[N:4][O:5][N:6]=1

Participants

7

Reactant 4

HCID 962WaterHCID 7856ChloroacetonitrileHCID 24758Sodium hydrideHCID 57721189HCID 57721189, compound

Product 1

HCID 59681773HCID 59681773, compoundYield 2.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution containing 150 mg of the product from Example 38 (0.51 mmols) in 2.6 mL of dry DMF was added 25 mg of NaH (0.61 mmols, 60% suspension in oil). After stirring at ambient temperature for 5 min, 0.033 mL of chloroacetonitrile (0.51 mmols) was added to the reaction via syringe. The reaction was warmed to 60° C. for 16 h. After cooling to room temperature, 1 mL of water was carefully added to the reaction mixture. The mixture was diluted with 20 mL of EtOAc and washed with 2N NaOH (3×10 mL). The organic layer was dried over MgSO4, filtered, and concentrated in vacuo. The residue was dissolved in a minimum volume of DMSO and filtered through a 0.45 m acrodisc filter. The resulting solution was purified on the Gilson reverse-phase HPLC to afford the title product (4 mg, 2%). MS (ES+) m/e 334 [M+H]+.

Workup

  1. temperatureThe reaction was warmed to 60° C. for 16 h
  2. temperatureAfter cooling to room temperature
  3. washwashed with 2N NaOH (3×10 mL)
  4. dry with materialThe organic layer was dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. dissolutionThe residue was dissolved in a minimum volume of DMSO
  8. filtrationfiltered through a 0.45 m
  9. filtrationacrodisc filter
  10. customThe resulting solution was purified on the Gilson reverse-phase HPLC

Sources & evidence

ORD record
ord-f4cd7fcc7762406d9e46b373a7498f59
Source dataset
uspto-grants-2008_03
Patent number
US07348339B2

Reaction notes

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