Water → Methyl 1H-pyrazolo[3,4-C]pyridine-5-carboxylate

HRID 2377069Notes

Reaction equation

HRID 2377069 reaction equation
[CH3:1][C:2]1[C:7]([N+:8]([O-])=O)=[CH:6][N:5]=[C:4]([C:11]([O:13][CH3:14])=[O:12])[CH:3]=1.[NH2:15]C1C(C)=CC(C(OC)=O)=NC=1.N([O-])=O.[Na+].O>C1COCC1.[Pd].CC(O)=O>[NH:8]1[C:7]2=[CH:6][N:5]=[C:4]([C:11]([O:13][CH3:14])=[O:12])[CH:3]=[C:2]2[CH:1]=[N:15]1

Participants

8

Reactant 4

HCID 962WaterHCID 20717632Methyl 4-methyl-5-nitropyridine-2-carboxylateHCID 23668193Sodium NitriteHCID 69199253Methyl 5-amino-4-methylpyridine-2-carboxylate

Product 1

HCID 59855813Methyl 1H-pyrazolo[3,4-C]pyridine-5-carboxylateYield 80.5%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 176Acetic AcidSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirring solution of methyl 4-methyl-5-nitro-pyridine-2-carboxylate (3.00 g) in THF (40 mL) was added Pd/C catalyst (300 mg). The flask was evacuated and back-filled with hydrogen from a balloon three times and then stirred under hydrogen overnight. The mixture was filtered through Celite, and the filter cake was extracted several times with ethyl acetate. The combined organic extracts were concentrated and the resulting white powder (2.58 g, 100%) consisting of methyl 5-amino-4-methyl-pyridine-2-carboxylate was used in the next step without further purification and characterization. To a stirring solution of methyl 5-amino-4-methyl-pyridine-2-carboxylate (2.58 g, 15.53 mmol) in AcOH (60 mL), was added 2.0 M sodium nitrite in water (9.3 mL, 18.63 mmol) and the mixture was stirred for 4 h at room temperature. The acetic acid and other volatiles were removed at high vacuum, the resulting solid was suspended in water and filtered to give the title compound as a yellowish solid (2.18 g, 79% yield). 1HNMR (DMSO-d6): δ ppm 13.98 (bs, 1H), 9.10 (s, 1H), 8.57 (s, 1H), 8.39 (s, 1H), 3.88 (s, 3H). LCMS (API-ES M+Na+) 200.

Workup

  1. customThe flask was evacuated
  2. additionback-filled with hydrogen from a balloon three times
  3. filtrationThe mixture was filtered through Celite
  4. extractionthe filter cake was extracted several times with ethyl acetate
  5. concentrationThe combined organic extracts were concentrated
  6. customwas used in the next step without further purification and characterization
  7. stirringthe mixture was stirred for 4 h at room temperature
  8. customThe acetic acid and other volatiles were removed at high vacuum
  9. filtrationfiltered

Sources & evidence

ORD record
ord-0fad31592f39414885b0d0aa0f9b1861
Source dataset
uspto-grants-2008_12
Patent number
US07468375B2

Reaction notes

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