Triethylamine → 4-Chloro-2-(methylthio)pyrazolo[1,5-a][1,3,5]triazine

HRID 624765Notes

Reaction equation

HRID 624765 reaction equation
[CH3:1][S:2][C:3]1[NH:8][C:7](=O)[N:6]2[N:10]=[CH:11][CH:12]=[C:5]2[N:4]=1.P(Cl)(Cl)([Cl:15])=O.C(N(CC)CC)C>C(#N)C>[Cl:15][C:7]1[N:6]2[N:10]=[CH:11][CH:12]=[C:5]2[N:4]=[C:3]([S:2][CH3:1])[N:8]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 24813Phosphorus oxychlorideHCID 1354442592-(Methylthio)pyrazolo[1,5-a][1,3,5]triazin-4(3H)-one

Product 1

HCID 129161154-Chloro-2-(methylthio)pyrazolo[1,5-a][1,3,5]triazineYield 71%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

In a round bottom flask equipped with a magnetic stirbar, 2-(methylthio)pyrazolo[1,5-a][1,3,5]triazin-4(3H)-one (1.0 eq, 10.43 g, 57.24 mmol) was suspended in acetonitrile (100 ml). Phosphorus oxychloride (4.0 eq, 21 ml, 229.4 mmol) and triethylamine (1.05 eq, 8.4 ml, 60.27 mmol) were added and the mixture stirred at reflux for 3.5 hours, at which time LCMS indicated completion of the reaction. The mixture was cooled down and slowly poured into crushed ice (final total volume of about 600 ml). The solid was filtered, washed with water and dried in a vacuum oven to afford 4-chloro-2-(methylthio)pyrazolo[1,5-a][1,3,5]triazine as a tan solid (8.15 g, 71% yield). LCMS (ES): >97% pure, m/z 201 [M+H]+.

Workup

  1. temperatureat reflux for 3.5 hours, at which time LCMS
  2. customcompletion of the reaction
  3. temperatureThe mixture was cooled down
  4. additionslowly poured
  5. custominto crushed ice (final total volume of about 600 ml)
  6. filtrationThe solid was filtered
  7. washwashed with water
  8. customdried in a vacuum oven

Sources & evidence

ORD record
ord-cd77b86bfe6c48ef917c8241596b5ffa
Source dataset
uspto-grants-2016_04
Patent number
US09303033B2

Reaction notes

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