Phosphorus oxychloride → 8-Chloro-5-(thiophen-2-yl)-[1,2,4]triazolo[4,3-a]pyrazine

HRID 1045722Notes

Reaction equation

HRID 1045722 reaction equation
CO[C:3]1[C:4]2[N:5]([CH:14]=[N:15][N:16]=2)[C:6]([C:9]2[S:10][CH:11]=[CH:12][CH:13]=2)=[CH:7][N:8]=1.O=P(Cl)(Cl)[Cl:19]>>[Cl:19][C:3]1[C:4]2[N:5]([CH:14]=[N:15][N:16]=2)[C:6]([C:9]2[S:10][CH:11]=[CH:12][CH:13]=2)=[CH:7][N:8]=1

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 584470378-Methoxy-5-(thiophen-2-yl)-[1,2,4]triazolo[4,3-a]pyrazine

Product 1

HCID 584469998-Chloro-5-(thiophen-2-yl)-[1,2,4]triazolo[4,3-a]pyrazineYield 75%

Conditions

Temperature
130 °C

Procedure

A 50 mL round bottom flask was charged with 8-methoxy-5-(thiophen-2-yl)-[1,2,4]triazolo[4,3-a]pyrazine (0.30 g, 1.3 mmol) and POCl3 (3 mL). The mixture was heated at 130° C. overnight. TLC indicated a complete conversion. Work-up: the reaction mixture was concentrated in vacuo. The residue was carefully poured into ice and extracted with EtOAc (10 mL). The organic layer was washed with saturated aqueous NaHCO3 and brine, dried over anhydrous Na2SO4, and concentrated in vacuo. The residue was further purified by flash column chromatography on silica gel with a 1:5 EtOAc/petroleum ether, to afford 0.23 g (75%) of the product as a white solid. MS m/z: 237 (M+H+).

Workup

  1. concentrationthe reaction mixture was concentrated in vacuo
  2. additionThe residue was carefully poured into ice
  3. extractionextracted with EtOAc (10 mL)
  4. washThe organic layer was washed with saturated aqueous NaHCO3 and brine
  5. dry with materialdried over anhydrous Na2SO4
  6. concentrationconcentrated in vacuo
  7. customThe residue was further purified by flash column chromatography on silica gel with a 1:5 EtOAc/petroleum ether

Sources & evidence

ORD record
ord-82627c5b08074c5fb33d8294fa3c34e8
Source dataset
uspto-grants-2013_10
Patent number
US08569300B2

Reaction notes

Loading…