Sodium Hydroxide → 7-Chloro-5-methyl-1H-pyrazolo[4,3-b]pyridine

HRID 1860429Notes

Reaction equation

HRID 1860429 reaction equation
[CH3:1][C:2]1[N:7]=[C:6]2[CH:8]=[N:9][NH:10][C:5]2=[C:4](O)[CH:3]=1.[OH-].[Na+].P(Cl)(Cl)([Cl:16])=O>>[CH3:1][C:2]1[N:7]=[C:6]2[CH:8]=[N:9][NH:10][C:5]2=[C:4]([Cl:16])[CH:3]=1

Participants

4

Reactant 3

HCID 14798Sodium HydroxideHCID 24813Phosphorus oxychlorideHCID 178428911HCID 178428911, compound

Product 1

HCID 116798717-Chloro-5-methyl-1H-pyrazolo[4,3-b]pyridineYield 87%

Procedure

The cyclized compound (12) (4.58 g, 30.7 mmol) in phosphorus oxychloride (30 mL) was heated at 110° C. for 30 minutes. The end of the reaction was checked by LC/MS (disappearance of 150, appearance of 168). After cooling down at room temperature, the reaction mixture was poured on ice and pH was adjusted with a 6N NaOH solution to pH=5. The solid was collected with filtration and the mother aqueous layer was extracted with ethyl acetate (3×250 ml). The above solid was dissolved in the combined organic phases, washed with a brine solution (1×250 ml) and dried with sodium sulfate, filtered and concentrated. The crude product was purified by running through a short silica gel chromatography column to give the desired product (13) as a pale yellow solid (4.50 g, 26.8 mmol, 87%). GC/MS: m/z=167 (100%);. LC/MS: [M+H]′=168.

Workup

  1. additionthe reaction mixture was poured on ice and pH
  2. filtrationThe solid was collected with filtration
  3. extractionthe mother aqueous layer was extracted with ethyl acetate (3×250 ml)
  4. dissolutionThe above solid was dissolved in the combined organic phases
  5. washwashed with a brine solution (1×250 ml)
  6. dry with materialdried with sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude product was purified

Sources & evidence

ORD record
ord-3d3d4ba9a6194b05a4a6334f6d37d990
Source dataset
uspto-grants-2003_03
Patent number
US06531475B1

Reaction notes

Loading…