Water → HCID 59311444, compound

HRID 1693326Notes

Reaction equation

HRID 1693326 reaction equation
[NH2:1][C:2]1[N:3]=[C:4]2[C:13]3[C:7]([CH2:8][CH:9]([C:14]#[N:15])[S:10][C:11]=3[N:12]=1)=[N:6][N:5]2[CH2:16][C:17]1[C:22]([CH3:23])=[C:21]([O:24][CH3:25])[C:20]([CH3:26])=[CH:19][N:18]=1.[CH:27]([N-]C(C)C)([CH3:29])[CH3:28].[Li+].C(Br)C#C.O>O1CCCC1>[NH2:1][C:2]1[N:3]=[C:4]2[C:13]3[C:7]([CH2:8][C:9]([CH2:29][C:27]#[CH:28])([C:14]#[N:15])[S:10][C:11]=3[N:12]=1)=[N:6][N:5]2[CH2:16][C:17]1[C:22]([CH3:23])=[C:21]([O:24][CH3:25])[C:20]([CH3:26])=[CH:19][N:18]=1

Participants

6

Reactant 4

HCID 962WaterHCID 7842Propargyl bromideHCID 2724682Lithium diisopropylamideHCID 24811285HCID 24811285, compound

Product 1

HCID 59311444HCID 59311444, compoundYield 99%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

4-Amino-2-[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]-7,8-dihydro-2H-6-thia-1,2,3,5-tetraazaacenaphthylene-7-carbonitrile of Example 4 (50 mg) was dissolved in tetrahydrofuran (5 ml). A 2 N solution of lithium diisopropylamide in tetrahydrofuran (0.050 ml) was added at −78° C., and the mixture was stirred at the same temperature for 15 minutes. Then, propargyl bromide (0.015 ml) was added and the mixture was stirred at the same temperature for three hours. Water was added to the reaction solution, and then the mixture was heated to room temperature, followed by extraction with ethyl acetate. The organic layer was dried over magnesium sulfate and filtered, and the filtrate was concentrated. The resulting residue was purified by reversed phase liquid chromatography. The resulting solid was dissolved in a 50% solution of trifluoroacetic acid in dichloromethane (1 ml), followed by stirring for one hour. The reaction solution was concentrated under reduced pressure and azeotropically distilled with ethanol. The resulting solid was washed with ether to obtain the title compound (2 mg, 99%) as a solid.

Workup

  1. stirringthe mixture was stirred at the same temperature for three hours
  2. extractionfollowed by extraction with ethyl acetate
  3. dry with materialThe organic layer was dried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationthe filtrate was concentrated
  6. customThe resulting residue was purified by reversed phase liquid chromatography
  7. dissolutionThe resulting solid was dissolved in a 50% solution of trifluoroacetic acid in dichloromethane (1 ml)
  8. stirringby stirring for one hour
  9. concentrationThe reaction solution was concentrated under reduced pressure
  10. distillationazeotropically distilled with ethanol
  11. washThe resulting solid was washed with ether

Sources & evidence

ORD record
ord-da14bf7467e24f959d0bc2483a69916a
Source dataset
uspto-grants-2012_04
Patent number
US08158638B2

Reaction notes

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