Water → 3-Cyclopentyl-2-(2-ethyl-2H-[1,2,4]triazol-3-ylmethoxy)-4-methyl-7-phenylpyrazolo[1,5-d][1,2,4]triazine

HRID 985427Notes

Reaction equation

HRID 985427 reaction equation
[CH:1]1([C:6]2[C:7]([O:22]S(C3C=CC(C)=CC=3)(=O)=O)=[N:8][N:9]3[C:14]=2[C:13]([CH3:15])=[N:12][N:11]=[C:10]3[C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[CH2:33]([N:35]1[C:39]([CH2:40]O)=[N:38][CH:37]=[N:36]1)[CH3:34].[H-].[Na+].O>CN(C=O)C>[CH:1]1([C:6]2[C:7]([O:22][CH2:40][C:39]3[N:35]([CH2:33][CH3:34])[N:36]=[CH:37][N:38]=3)=[N:8][N:9]3[C:14]=2[C:13]([CH3:15])=[N:12][N:11]=[C:10]3[C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 11412385(1-ethyl-1H-1,2,4-triazol-5-yl)methanolHCID 86587509Toluene-4-sulfonic acid 3-cyclopentyl-4-methyl-7-phenylpyrazolo[1,5-d][1,2,4]triazin-2-yl ester

Product 1

HCID 101580323-Cyclopentyl-2-(2-ethyl-2H-[1,2,4]triazol-3-ylmethoxy)-4-methyl-7-phenylpyrazolo[1,5-d][1,2,4]triazine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To toluene-4-sulfonic acid 3-cyclopentyl-4-methyl-7-phenylpyrazolo[1,5-d][1,2,4]triazin-2-yl ester (300 mg, 0.67 mmol) and (2-ethyl-2H-[1,2,4]triazol-3-yl)methanol (102 mg, 1.2 molar eq; prepared as described in EP-A-170073) in DMF (10 ml) was added sodium hydride (29.5 mg of a 60% dispersion in mineral oil; 1.2 molar eq) and the mixture was stirred at room temperature for 1 h. Water (90 ml) was added then the solution was extracted with diethyl ether (4×60 ml). The combined ether layers were washed with brine (1×100 ml), dried (Na2SO4), the solvent was removed in vacuo and the residue was purified by flash chromatography on silica gel eluting with 0 to 50% ethyl acetate in dichloromethane. 3-Cyclopentyl-2-(2-ethyl-2H-[1,2,4]triazol-3-ylmethoxy)-4-methyl-7-phenylpyrazolo[1,5-d][1,2,4]triazine was isolated as a gum, which solidified upon trituration under diethyl ether/isohexane (144 mg, mp=112° C.). 1H NMR (360 MHz, CDCl3) δ 1.42 (3H, t, J=7.3 Hz), 1.66-1.95 (8H, m), 2.87 (3H, s), 3.43 (1H, m), 4.20 (2H, q, J=7.3 Hz), 5.55 (2H, s), 7.51-7.61 (3H, m), 7.93 (1H, s), 8.28-8.31 (2H, m); MS (ES+) m/e 403 [MH]+. Anal. Found C, 65.10; H, 6.06; N, 24.19%. C22H25N7O requires C, 65.49; H, 6.25; N, 24.06%.

Workup

  1. extractionthe solution was extracted with diethyl ether (4×60 ml)
  2. washThe combined ether layers were washed with brine (1×100 ml)
  3. dry with materialdried (Na2SO4)
  4. customthe solvent was removed in vacuo
  5. customthe residue was purified by flash chromatography on silica gel eluting with 0 to 50% ethyl acetate in dichloromethane

Sources & evidence

ORD record
ord-8f5605ba33144a839d3dea496673e68a
Source dataset
uspto-grants-2005_03
Patent number
US06872720B2

Reaction notes

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