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

HRID 985425Notes

Reaction equation

HRID 985425 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.[CH3:34][N:35]1[C:39]([CH2:40]O)=[N:38][CH:37]=[N:36]1.[H-].[Na+].O>CN(C=O)C>[CH:1]1([C:6]2[C:7]([O:23][CH2:40][C:39]3[N:35]([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][C:17]=2[F:22])[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 11073377(1-methyl-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 102948213-Cyclopentyl-7-(2-fluorophenyl)-4-methyl-2-(2-methyl-2H-[1,2,4]triazol-3-ylmethoxy)pyrazolo[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 (Example 3, step c; 230 mg, 0.494 mmol) and (2-methyl-2H-[1,2,4]triazol-3-yl)methanol (67 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-7-(2-fluorophenyl)-4-methyl-2-(2-methyl-2H-[1,2,4]triazol-3-ylmethoxy)pyrazolo[1,5-d][1,2,4]triazine was isolated as a gum, which solidified upon trituration under diethyl ether/isohexane (77 mg, mp=123° C.). 1H NMR (360 MHz, CDCl3) δ 1.60-1.98 (8H, m), 2.88 (3H, s), 3.42 (1H, m), 3.73 (3H, s), 5.44 (2H, s), 7.22-7.37 (2H, m), 7.56-7.71 (2H, m), 7.85 (1H, s); MS (ES+) m/e 408 [MH]+. Anal. Found C, 61.64; H, 5.31; N, 23.77%. C21H22FN7O requires C, 61.90; H, 5.44; N, 24.06%.

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-a79be130185d48029f659b3235549055
Source dataset
uspto-grants-2005_03
Patent number
US06872720B2

Reaction notes

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