Diethyl Carbonate → 7-(2-Chlorophenyl)-2-methyl-3H-pyrazolo[1,5-a][1,3,5]triazin-4-one

HRID 2054381Notes

Reaction equation

HRID 2054381 reaction equation
[O-]CC.[Na+].[Na].[C:6]([OH:9])(=O)C.[Cl:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[C:17]1[CH:18]=[C:19]([NH:22][C:23](=[NH:25])[CH3:24])[NH:20][N:21]=1.C(OC(=O)OCC)C>C(O)C>[Cl:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[C:17]1[CH:18]=[C:19]2[N:22]=[C:23]([CH3:24])[NH:25][C:6](=[O:9])[N:20]2[N:21]=1

Participants

6

Reactant 4

HCID 7766Diethyl CarbonateHCID 2723922Sodium ethoxideHCID 5360545SodiumHCID 178465555HCID 178465555, compound

Product 1

HCID 1359745387-(2-Chlorophenyl)-2-methyl-3H-pyrazolo[1,5-a][1,3,5]triazin-4-oneYield 84.3%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To an ethanolic solution of sodium ethoxide, generated by portionwise addition of sodium metal (10.5 g, 455 mmol) to stirred ethanol (450 ml), was added N-[5-(2-chlorophenyl)-2H-pyrazol-3-yl]-acetamidine, acetate salt (I-1A-1b; 13.4 g, 45.5 mmol) in one portion. Diethylcarbonate (44.1 ml, 364 mmol) was added, dropwise, and the mixture was heated to reflux, overnight. After cooling to room temperature, the reaction was concentrated, in vacuo, and then extracted with ethyl acetate from water, adjusted to pH 6 with 3 M aqueous HCL. The combined organic layers were washed with brine, dried (MgSO4), filtered, and then concentrated, in vacuo, to afford the crude product as an off-white solid (11.0 g). The solids were triturated from ethyl acetate (100 ml), the supernate was decanted away, the solids were washed with additional ethyl acetate (100 ml) and then dried, in vacuo, to afford I-1A-1c as a colorless solid (10.0 g, 84%): +APcI MS (M+1) 261.2; 1H NMR (400 MHz, CD3OD) δ 7.84-7.81 (m, 1H), 7.54-7.51 (m, 1H), 7.44-7.38 (m, 2H), 6.77 (s, 1H), 2.42 (s, 3H).

Workup

  1. temperaturedropwise, and the mixture was heated
  2. temperatureto reflux, overnight
  3. concentrationthe reaction was concentrated, in vacuo
  4. extractionextracted with ethyl acetate from water
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated, in vacuo
  9. customto afford the crude product as an off-white solid (11.0 g)
  10. customThe solids were triturated from ethyl acetate (100 ml)
  11. customthe supernate was decanted away
  12. washthe solids were washed with additional ethyl acetate (100 ml)
  13. customdried, in vacuo

Sources & evidence

ORD record
ord-2f695eae7cc6493e8849a579233dab19
Source dataset
uspto-grants-2008_02
Patent number
US07329658B2

Reaction notes

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