Phosphorus oxychloride → ethyl 4-chloro-1-ethyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylate

HRID 451206

Reaction equation

HRID 451206 reaction equation
C(O[C:4](=O)[C:5](=[CH:11][NH:12][C:13]1[N:14]([CH2:18][CH3:19])[N:15]=[CH:16][CH:17]=1)[C:6]([O:8][CH2:9][CH3:10])=[O:7])C.O=P(Cl)(Cl)[Cl:23]>>[CH2:9]([O:8][C:6]([C:5]1[C:4]([Cl:23])=[C:17]2[CH:16]=[N:15][N:14]([CH2:18][CH3:19])[C:13]2=[N:12][CH:11]=1)=[O:7])[CH3:10]

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 12845080Diethyl {[(1-ethyl-1H-pyrazol-5-yl)amino]methylene}malonate

Product 1

HCID 10491120ethyl 4-chloro-1-ethyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylateYield 69%

Conditions

Temperature
135 °C

Procedure

A solution of 2-[(2-ethyl-2H-pyrazol-3-ylamino)-methylene]-malonic acid diethyl ester (11.75 g, 0.041 mol) in POCl3 (70 mL) was heated at reflux (135° C.) for 8 hours. The excess of POCl3 were distilled off and the reaction mixture cooled to 0° C., before careful addition of water (100 mL) and then aqueous NaOH (3N) until pH reached 7. The product was extracted with CH2Cl2 several times, and the combined orgnic phase were dried over Na2SO4 and concentrated under vacuo. Column chromatography (SiO2, EtOAc/Heptane 1/5) afforded 7.22 g (69%) of the title product as a white solid. ES-MS m/e: 254.2 (M+H+).

Workup

  1. distillationThe excess of POCl3 were distilled off
  2. temperaturethe reaction mixture cooled to 0° C., before careful addition of water (100 mL)
  3. extractionThe product was extracted with CH2Cl2 several times
  4. dry with materialthe combined orgnic phase were dried over Na2SO4
  5. concentrationconcentrated under vacuo

Sources & evidence

ORD record
ord-9179ab2bd5b84a39a150d267fd730d56
Source dataset
uspto-grants-2013_07
Patent number
US08487102B2

Linked notes

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