Phosphorus oxychloride → Ethyl 1-benzyl-4-chloro-1H-pyrazolo[3,4-B]pyridine-5-carboxylate

HRID 451214Notes

Reaction equation

HRID 451214 reaction equation
C(O[C:4](=O)[C:5](=[CH:11][NH:12][C:13]1[N:14]([CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[N:15]=[CH:16][CH:17]=1)[C:6]([O:8][CH2:9][CH3:10])=[O:7])C.O=P(Cl)(Cl)[Cl:28]>>[CH2:9]([O:8][C:6]([C:5]1[C:4]([Cl:28])=[C:17]2[CH:16]=[N:15][N:14]([CH2:18][C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=3)[C:13]2=[N:12][CH:11]=1)=[O:7])[CH3:10]

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 128450792-[(2-Benzyl-2H-pyrazol-3-ylamino)-methylene]-malonic acid diethyl ester

Product 1

HCID 21823886Ethyl 1-benzyl-4-chloro-1H-pyrazolo[3,4-B]pyridine-5-carboxylateYield 65%

Conditions

Temperature
130 °C

Procedure

A solution of 2-[(2-benzyl-2H-pyrazol-3-ylamino)-methylene]-malonic acid diethyl ester (7.0 g, 0.020 mol) in POCl3 (50 mL) was heated at reflux (130° 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 1/6) afforded 4.10 g (65%) of the title product as a white solid.

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-67ec87bf21464626831ff4e133ca432b
Source dataset
uspto-grants-2013_07
Patent number
US08487102B2

Reaction notes

Loading…