Dimethylformamide → HCID 18008982, compound

HRID 987510Notes

Reaction equation

HRID 987510 reaction equation
[CH3:1][C:2]1(C(O)=O)[CH:6]=[CH:5][N:4]([C:7]2[C:16]([F:17])=[CH:15][C:14]3[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=3)[CH:8]=2)[NH:3]1.C[N:22](C=O)C.C(Cl)(=O)C(Cl)=O.[N-]=[N+]=[N-].[Na+]>C(Cl)Cl.O.O1CCOCC1>[CH3:1][C:2]1[CH:6]=[C:5]([NH2:22])[N:4]([C:7]2[C:16]([F:17])=[CH:15][C:14]3[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=3)[CH:8]=2)[N:3]=1

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 33557Sodium AzideHCID 65578Oxalyl chlorideHCID 69889855HCID 69889855, compound

Product 1

HCID 18008982HCID 18008982, compoundYield 38%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

3-Methyl-1-(3-fluoro-2-naphthyl)-1H-pyrazole-5-carboxylic acid (see Step 1, Example 4) (828 mg, 3.1 mmol) was dissolved in 20 mL dry DCM. To it were added 0.05 mL DMF and oxalyl chloride (0.81 mL, 9.3 mL). The mixture was stirred for 2 hrs. It was evaporated in vacuuo. The residue was dissolved in 30 mL dry dioxane. It was chilled in ice bath. To the stirred cold mixture was added dropwise a chilled solution of sodium azide (0.4 g, 6.2 mmol) in 2 mL water and 1 mL dioxane. Reaction was allowed for 1 hr. It was evaporated in vacuuo. The residue was taken into EtOAc and washed with water ×2. The organic phase was dried and concentrated in vacuuo. The organic residue was then dissolved in 30 mL DMF. To it was added 15 mL water. The mixture was refluxed for 2.5 hrs. It was concentrated in vacuuo and purified using flash column to give 3-methyl-1-(3-fluoro-2-naphthyl)-5-amino-1H-pyrazole (280 mg, 38% overall). Rf 0.45 (1:1 EtOAc:hexane). ES-MS: (M+H)+242.

Workup

  1. customIt was evaporated in vacuuo
  2. dissolutionThe residue was dissolved in 30 mL dry dioxane
  3. temperatureIt was chilled in ice bath
  4. customReaction
  5. waitwas allowed for 1 hr
  6. customIt was evaporated in vacuuo
  7. washwashed with water ×2
  8. customThe organic phase was dried
  9. concentrationconcentrated in vacuuo
  10. dissolutionThe organic residue was then dissolved in 30 mL DMF
  11. additionTo it was added 15 mL water
  12. temperatureThe mixture was refluxed for 2.5 hrs
  13. concentrationIt was concentrated in vacuuo
  14. custompurified

Sources & evidence

ORD record
ord-c6056ab71f1044d088ae404a4ac291f3
Source dataset
uspto-grants-2003_10
Patent number
US06632815B2

Reaction notes

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