3-Amino-2-chloro-4-methylpyridine → 7-Chloro-1H-pyrazolo[3,4-c]pyridine

HRID 1527296Notes

Reaction equation

HRID 1527296 reaction equation
[Cl:1][C:2]1[C:7]([NH2:8])=[C:6]([CH3:9])[CH:5]=[CH:4][N:3]=1.[N:10]([O-])=O.[Na+]>C(O)(=O)C.O>[Cl:1][C:2]1[N:3]=[CH:4][CH:5]=[C:6]2[CH:9]=[N:10][NH:8][C:7]=12

Participants

5

Reactant 2

HCID 27563873-Amino-2-chloro-4-methylpyridineHCID 23668193Sodium Nitrite2×

Product 1

HCID 126684917-Chloro-1H-pyrazolo[3,4-c]pyridine

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 962WaterSolvent2×

Procedure

A solution of 2-chloro-4-methylpyridin-3-amine [133627-45-9] (3.0 g, 21.0 mmol) in acetic acid (300 mL) was treated with a solution of sodium nitrite (1.45 g, 21.0 mmol) in water (2.5 mL). The reaction mixture was stirred at rt for 15 min then allowed to stand at ambient temperature for 24 h. An additional solution of sodium nitrite (500 mg, 7.25 mmol) in water (1 mL) was added to the mixture which was allowed to stand at rt for 3 h. Acetic acid was evaporated under reduced pressure and the residual aqueous solution was partitioned between EtOAc and sat. aq. NaHCO3. The insoluble solid was filtered off (dried under vacuum; batch 1) and the organic filtrate was washed with water and brine, then dried (Phase separator) and concentrated under vacuum (batch 2). The two batches were combined to give 7-chloro-1H-pyrazolo[3,4-c]pyridine as a solid. MS (LC-MS): 153 [M+H]+, tR (HPLC conditions k): 0.9 min.

Workup

  1. waitto stand at ambient temperature for 24 h
  2. waitto stand at rt for 3 h
  3. customAcetic acid was evaporated under reduced pressure
  4. customthe residual aqueous solution was partitioned between EtOAc and sat. aq. NaHCO3
  5. filtrationThe insoluble solid was filtered off
  6. custom(dried under vacuum; batch 1)
  7. washthe organic filtrate was washed with water and brine
  8. customdried (Phase separator)
  9. concentrationconcentrated under vacuum (batch 2)

Sources & evidence

ORD record
ord-dc7507fad2924ca2962f71c045b8a6b2
Source dataset
uspto-grants-2015_07
Patent number
US09085555B2

Reaction notes

Loading…