Ammonia → HCID 68913731, compound

HRID 1455276Notes

Reaction equation

HRID 1455276 reaction equation
[C:1]([C:3]1[CH:22]=[CH:21][C:6]([O:7][C:8]2[C:9]([O:19][CH3:20])=[N:10][N:11]([CH2:15][C:16](O)=[O:17])[C:12]=2[CH2:13][CH3:14])=[CH:5][CH:4]=1)#[N:2].C(Cl)(=O)C(Cl)=O.[NH3:29]>ClCCl.O1CCOCC1>[C:1]([C:3]1[CH:22]=[CH:21][C:6]([O:7][C:8]2[C:9]([O:19][CH3:20])=[N:10][N:11]([CH2:15][C:16]([NH2:29])=[O:17])[C:12]=2[CH2:13][CH3:14])=[CH:5][CH:4]=1)#[N:2]

Participants

6

Reactant 3

HCID 222AmmoniaHCID 65578Oxalyl chlorideHCID 68914119HCID 68914119, compound

Product 1

HCID 68913731HCID 68913731, compoundYield 17%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

The acid of step (b) above (180 mg, 0.6 mmol) was suspended in dichloromethane (5 ml), and oxalyl chloride (150 μl, 1.72 mmol) was added, resulting in gas evolution. The reaction mixture was stirred at room temperature for 1 hour, under nitrogen. The solvent was then evaporated under reduced pressure and the residue was azeotroped with toluene 3 times. The crude intermediate acid chloride was carried straight through to the next step. It was dissolved in tetrahydrofuran (2 ml), and ammonia 0.5M in dioxane (10 ml) was added. After stirring overnight at room temperature, analysis by TLC showed little product had formed. A further portion of fresh 0.5M ammonia in dioxane (10 ml) was added to the reaction mixture and stirring was continued for another overnight period. The reaction mixture was evaporated and the residue was partitioned between dichloromethane (20 ml) and aqueous sodium bicarbonate (10 ml). The organic layer was separated and the aqueous layer was extracted 3 times with dichloromethane (10 ml). The organic extracts were combined, dried over magnesium sulphate, filtered and evaporated under reduced pressure. The crude product was purified by flash chromatography on silica gel eluting with ethyl acetate to provide the title compound (20 mg, 17%).

Workup

  1. customresulting in gas evolution
  2. customThe solvent was then evaporated under reduced pressure
  3. customthe residue was azeotroped with toluene 3 times
  4. dissolutionIt was dissolved in tetrahydrofuran (2 ml)
  5. additionammonia 0.5M in dioxane (10 ml) was added
  6. stirringAfter stirring overnight at room temperature
  7. customhad formed
  8. stirringstirring
  9. waitwas continued for another overnight period
  10. customThe reaction mixture was evaporated
  11. customthe residue was partitioned between dichloromethane (20 ml) and aqueous sodium bicarbonate (10 ml)
  12. customThe organic layer was separated
  13. extractionthe aqueous layer was extracted 3 times with dichloromethane (10 ml)
  14. dry with materialdried over magnesium sulphate
  15. filtrationfiltered
  16. customevaporated under reduced pressure
  17. customThe crude product was purified by flash chromatography on silica gel eluting with ethyl acetate

Sources & evidence

ORD record
ord-bde27aa60d25487fad28861af2cd041c
Source dataset
uspto-grants-2009_01
Patent number
US07482375B2

Reaction notes

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