Methanol → 2-(6-Methoxypyrimidin-4-yl)-4-(1H-1,2,3-triazol-1-yl)-1,2-dihydro-3H-pyrazol-3-one hydrochloride

HRID 242294Notes

Reaction equation

HRID 242294 reaction equation
CO.O1[CH2:8][CH2:7][O:6][CH2:5]C1.Cl.[Cl:10]C1[N:16]=[CH:15][N:14]=[C:13]([N:17]2[C:21](=[O:22])[C:20]([N:23]3[CH:27]=[CH:26][N:25]=[N:24]3)=[CH:19][NH:18]2)C=1>C1COCC1>[ClH:10].[CH3:5][O:6][C:7]1[N:16]=[CH:15][N:14]=[C:13]([N:17]2[C:21](=[O:22])[C:20]([N:23]3[CH:27]=[CH:26][N:25]=[N:24]3)=[CH:19][NH:18]2)[CH:8]=1

Participants

5

Reactant 3

HCID 887Methanol2×HCID 312751,4-DioxaneHCID 866352542-(6-Chloropyrimidin-4-yl)-4-(1H-1,2,3-triazol-1-yl)-1,2-dihydro-3H-pyrazol-3-one hydrochloride

Product 1

HCID 674547802-(6-Methoxypyrimidin-4-yl)-4-(1H-1,2,3-triazol-1-yl)-1,2-dihydro-3H-pyrazol-3-one hydrochloride

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

0.3 ml (6.6 mmol) methanol are initially introduced into 15 ml dioxane. 1.3 ml (2.7 mmol) of a 2 M solution of the phosphazene base P2-tert-butyl in THF are added slowly, while stirring, and the mixture is stirred at RT for 15 min. 350 mg (1.3 mmol) of the compound from Example 52A are subsequently added and the mixture is reacted in a single mode microwave (CEM Explorer) at 150° C. for 2 h. A further 2 ml (49.2 mmol) methanol are then added and the mixture is reacted again in a single mode microwave (CEM Explorer) under the same conditions for 2 h. After cooling, the reaction mixture is concentrated and the residue is purified via preparative HPLC (RP18 column; mobile phase: acetonitrile/water gradient with addition of 0.1% TFA). The product-containing fractions are combined and the mixture is concentrated on a rotary evaporator. The residue is dried under a high vacuum and 3 ml of a 4 N solution of hydrogen chloride in dioxane is subsequently added. The mixture is stirred at RT for 30 min and the solid is then filtered off and dried under a high vacuum.

Workup

  1. stirringthe mixture is stirred at RT for 15 min
  2. customthe mixture is reacted in a single mode microwave (CEM Explorer) at 150° C. for 2 h
  3. customthe mixture is reacted again in a single mode microwave (CEM Explorer) under the same conditions for 2 h
  4. temperatureAfter cooling
  5. concentrationthe reaction mixture is concentrated
  6. customthe residue is purified via preparative HPLC (RP18 column; mobile phase: acetonitrile/water gradient with addition of 0.1% TFA)
  7. concentrationthe mixture is concentrated on a rotary evaporator
  8. dry with materialThe residue is dried under a high vacuum and 3 ml of a 4 N solution of hydrogen chloride in dioxane
  9. additionis subsequently added
  10. stirringThe mixture is stirred at RT for 30 min
  11. filtrationthe solid is then filtered off
  12. customdried under a high vacuum

Sources & evidence

ORD record
ord-ebfd2bf810784f4ca89b7a2eb121a87a
Source dataset
uspto-grants-2014_02
Patent number
US08653111B2

Reaction notes

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