Hydrazine hydrate (1:1) → HCID 178434440, compound

HRID 1916460Notes

Reaction equation

HRID 1916460 reaction equation
Cl[C:2]1[C:7]([C:8](=O)[CH3:9])=[CH:6][CH:5]=[CH:4][N:3]=1.O.[NH2:12][NH2:13]>CCCCO>[CH3:9][C:8]1[C:7]2[C:2](=[N:3][CH:4]=[CH:5][CH:6]=2)[NH:13][N:12]=1

Participants

4

Reactant 2

HCID 24654Hydrazine hydrate (1:1)HCID 109426973-Acetyl-2-chloropyridine

Product 1

HCID 178434440HCID 178434440, compound

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of the above crude 1-(2-chloropyridin-3-yl)ethanone (XIII) in n-BuOH (512 L) was added 85% hydrazine hydrate (78 L, 1360 mol). The reaction was heated at refluxed (˜120° C.) for 48 hours. The reaction was cooled and evaporated under vacuum. The crude material was taken up in DCM (834 L) and washed with 2× aqueous 25% NaCl (214 L) by adding aqueous 25% NaCl, stirring for 50 min, allowing to stand for 50 min, separating the layers and then repeating. The organic layer was evaporated to produce 3-methyl-1H-pyrazolo[3,4-b]pyridine (XIV) as a solid (13.2 Kg, 99 mol, 94.1% purity, 36.3% assay yield for 3 steps). 1H NMR (DMSO-d6, 400 MHz) δ ppm 2.50 (s, 3H), 7.13 (dd, J=4.4 Hz, J=8 Hz, 1H), 8.19 (dd, J=1.2 Hz, J=8 Hz, 1H), 8.47 (dd, J=1.6 Hz, J=4.8 Hz, 1H), 13.18 (brs, 1H); ESIMS found C7H7N3 m/z 133.8 (M+H).

Workup

  1. temperatureThe reaction was heated
  2. temperatureThe reaction was cooled
  3. customevaporated under vacuum
  4. washwashed with 2× aqueous 25% NaCl (214 L)
  5. additionby adding aqueous 25% NaCl
  6. waitto stand for 50 min
  7. customseparating the layers
  8. customThe organic layer was evaporated
  9. customto produce

Sources & evidence

ORD record
ord-83f0ef1834024410b640d5c0637a1172
Source dataset
uspto-grants-2013_12
Patent number
US08618128B1

Reaction notes

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