Sodium Hydroxide → 3-Nitropyrazolo(1,5-a)pyridine

HRID 859129Notes

Reaction equation

HRID 859129 reaction equation
[N:1]1[N:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]2=[CH:3][CH:2]=1.[N+:10]([O-])([O-:12])=[O:11].[NH4+].[OH-].[Na+].C(=O)(O)[O-].[Na+]>S(=O)(=O)(O)O.CCOCC.O>[N+:10]([C:3]1[CH:2]=[N:1][N:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=12)([O-:12])=[O:11]

Participants

8

Reactant 4

HCID 14798Sodium HydroxideHCID 22985Ammonium nitrateHCID 67507Pyrazolo(1,5-a)pyridineHCID 516892Sodium Bicarbonate

Product 1

HCID 143613453-Nitropyrazolo(1,5-a)pyridineYield 76.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1118Sulfuric AcidSolvent2×HCID 3283Diethyl EtherSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of pyrazolo[1,5-a]pyridine (2.36 g, 20.0 mmol) (Lober, S. et al J. Med. Chem. 2001, 44, 2691) in concentrated sulfuric acid (20.0 mL) was added the freshly prepared solution of ammonium nitrate (1.84 g, 23.0 mmol) in concentrated sulfuric acid (25.0 mL) dropwise at −5° C. The resulting mixture was stirred at 0° C. for 2 h and added dropwise to a solution of 4 N sodium hydroxide (200 mL) at 0° C. followed by the addition of sodium bicarbonate (60.0 g). Water and ether were added and separated. The aqueous solution was extracted with dichloromethane (2×). The combined organic solution was dried (MgSO4) and filtered. The filtrate was concentrated in vacuo to dryness to give 2.49 g (76%) of beige solid as the title compound: mp 179–182° C. (CH2Cl2/hexanes); 1H NMR (400 MHz, CDCl3) δ 8.68 (s, 1H), 8.63 (dd, J=2.0, 6.9 Hz, 1H), 8.41 (dd, J=2.3, 8.9 Hz, 1H), 7.74 (dd, J=7.0, 8.9 Hz, 1H), 7.21 (dd, J=7.0, 7.0 Hz, 1H); IR (diffuse reflectance) 2480, 2465, 2417, 2392, 2350, 1636, 1512, 1479, 1464, 1408, 1288, 1252, 1194, 882, 773 cm−1; MS (EI) m/z 163 (M+); HRMS (FAB) calcd for C7H5N3O2+H 164.0460. found 164.0459; Anal. Calcd for C7H5N3O2: C, 51.54; H, 3.09; N, 25.76. Found: C, 51.42; H, 2.95; N, 25.71.

Workup

  1. customseparated
  2. extractionThe aqueous solution was extracted with dichloromethane (2×)
  3. dry with materialThe combined organic solution was dried (MgSO4)
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated in vacuo to dryness

Sources & evidence

ORD record
ord-c7292a78f5674c858a9ba0baf6e7c4ac
Source dataset
uspto-grants-2006_12
Patent number
US07151109B2

Reaction notes

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