Nitric Acid → Ethyl 1-(1-methylethyl)-6-(2-nitrophenyl)-1H-pyrazolo[3,4-b]pyridine-4-carboxylate

HRID 1522514Notes

Reaction equation

HRID 1522514 reaction equation
[CH3:1][CH:2]([N:4]1[C:8]2[N:9]=[C:10]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[CH:11]=[C:12]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[C:7]=2[CH:6]=[N:5]1)[CH3:3].S(=O)(=O)(O)O.C([O-])([O-])=O.[Na+].[Na+].[N+:35]([O-])([OH:37])=[O:36]>O>[CH3:1][CH:2]([N:4]1[C:8]2[N:9]=[C:10]([C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][C:23]=3[N+:35]([O-:37])=[O:36])[CH:11]=[C:12]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[C:7]=2[CH:6]=[N:5]1)[CH3:3]

Participants

6

Reactant 4

HCID 944Nitric AcidHCID 1118Sulfuric AcidHCID 10340Sodium CarbonateHCID 46538388Ethyl 1-(1-methylethyl)-6-phenyl-1H-pyrazolo[3,4-b]pyridine-4-carboxylate

Product 1

HCID 68078805Ethyl 1-(1-methylethyl)-6-(2-nitrophenyl)-1H-pyrazolo[3,4-b]pyridine-4-carboxylate

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Ethyl 1-(1-methylethyl)-6-phenyl-1H-pyrazolo[3,4-b]pyridine-4-carboxylate (120 mg, 0.388 mmol) was dissolved in concentrated nitric acid (1.7 mL) followed by addition of concentrated sulfuric acid (0.200 mL), and the reaction mixture was stirred at room temperature. After 40 min., the reaction mixture was cooled in an ice bath and with stirring was diluted with water (3 mL) and then slowly with saturated Na2CO3 (1 mL). The reaction mixture was extracted with EtOAc (2×6 mL). The combined organic layers were concentrated in vacuo and the crude product purified by silica gel chromatography (eluent: EtOAc/Hexanes, 0-70% gradient). The product, was collected as a white solid (35 mg, 26%). LCMS E-S (M+H)=355.2. 1H NMR (400 MHz, CHLOROFORM-d) 8.46 (s, 1H), 7.99 (s, 1H), 7.94 (dd, J=1.14, 7.96 Hz, 1H), 7.76-7.81 (m, 1H), 7.73 (td, J=1.26, 7.58 Hz, 1H), 7.59-7.66 (m, 1H), 5.25 (ddd, J=6.57, 6.69, 13.52 Hz, 1H), 4.51-4.59 (m, 2H), 1.61 (d, J=6.82 Hz, 6H), 1.52 (t, J=7.07 Hz, 3H).

Workup

  1. temperaturethe reaction mixture was cooled in an ice bath
  2. stirringwith stirring
  3. extractionThe reaction mixture was extracted with EtOAc (2×6 mL)
  4. concentrationThe combined organic layers were concentrated in vacuo
  5. customthe crude product purified by silica gel chromatography (eluent: EtOAc/Hexanes, 0-70% gradient)
  6. customThe product, was collected as a white solid (35 mg, 26%)

Sources & evidence

ORD record
ord-36cf3ef5eeff43adb2a776468988be78
Source dataset
uspto-grants-2015_07
Patent number
US09073924B2

Reaction notes

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