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

HRID 985424Notes

Reaction equation

HRID 985424 reaction equation
[CH:1]1([C:6]2[C:7]([O:23]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][C:17]=2[F:22])[CH2:5][CH2:4][CH2:3][CH2:2]1.[CH2:34]([N:36]1[C:40]([CH2:41]O)=[N:39][CH:38]=[N:37]1)[CH3:35].[H-].[Na+].O>CN(C=O)C>[CH:1]1([C:6]2[C:7]([O:23][CH2:41][C:40]3[N:36]([CH2:34][CH3:35])[N:37]=[CH:38][N:39]=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][C:17]=2[F:22])[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 11412385(1-ethyl-1H-1,2,4-triazol-5-yl)methanolHCID 86587508Toluene-4-sulfonic acid 3-cyclopentyl-7-(2-fluorophenyl)-4-methylpyrazolo[1,5-d][1,2,4]triazin-2-yl ester

Product 1

HCID 102239653-Cyclopentyl-2-(2-ethyl-2H-[1,2,4]triazol-3-ylmethoxy)-7-(2-fluorophenyl)-4-methylpyrazolo[1,5-d][1,2,4]triazine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To toluene-4-sulfonic acid 3-cyclopentyl-7-(2-fluorophenyl)-4-methylpyrazolo[1,5-d][1,2,4]triazin-2-yl ester (230 mg, 0.494 mmol) and (2-ethyl-2H-[1,2,4]triazol-3-yl)methanol (75.6 mg, 1.2 molar eq; prepared as described in EP-A-170073) in DMF (10 ml) was added sodium hydride (22 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 (4×50 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)-7-(2-fluorophenyl)-4-methylpyrazolo[1,5-d][1,2,4]triazine was isolated as a gum, which solidified upon trituration under diethyl ether/isohexane (34.5 mg, mp =105° C.). 1H NMR (360 MHz, CDCl3) δ 1.36 (3H, t, J=7.3 Hz), 1.53-1.91 (8H, m), 2.87 (3H, s), 3.41 (1H, m), 4.10 (2H, q, J=7.3 Hz), 5.45 (2H, s), 7.23-7.36 (2H, m), 7.58-7.75 (2H, m), 7.88 (1H, s); MS (ES+) m/e 422 [MH]+. Anal. Found C, 62.56; H, 5.67; N, 23.18%. C22H24FN7O requires C, 62.69; H, 5.74; N, 23.26%.

Workup

  1. extractionthe solution was extracted with diethyl ether (4×50 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-9d5daa51221144af88acfd1c1e32e633
Source dataset
uspto-grants-2005_03
Patent number
US06872720B2

Reaction notes

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