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

HRID 985433Notes

Reaction equation

HRID 985433 reaction equation
[C:1]([C:5]1[C:6]([O:23]S(C2C=CC(C)=CC=2)(=O)=O)=[N:7][N:8]2[C:13]=1[C:12]([CH3:14])=[N:11][N:10]=[C:9]2[C:15]1[CH:20]=[C:19]([F:21])[CH:18]=[CH:17][C:16]=1[F:22])([CH3:4])([CH3:3])[CH3:2].[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>[C:1]([C:5]1[C:6]([O:23][CH2:41][C:40]2[N:36]([CH2:34][CH3:35])[N:37]=[CH:38][N:39]=2)=[N:7][N:8]2[C:13]=1[C:12]([CH3:14])=[N:11][N:10]=[C:9]2[C:15]1[CH:20]=[C:19]([F:21])[CH:18]=[CH:17][C:16]=1[F:22])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 11412385(1-ethyl-1H-1,2,4-triazol-5-yl)methanolHCID 86587510Toluene-4-sulfonic acid 3-tert-butyl-7-(2,5-difluorophenyl)-4-methylpyrazolo[1,5-d][1,2,4]triazin-2-yl ester

Product 1

HCID 101133163-tert-Butyl-7-(2,5-difluorophenyl)-2-(2-ethyl-2H-[1,2,4]triazol-3-ylmethoxy)-4-methylpyrazolo[1,5-d][1,2,4]triazine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To toluene-4-sulfonic acid 3-tert-butyl-7-(2,5-difluorophenyl)-4-methylpyrazolo[1,5-d][1,2,4]triazin-2-yl ester (0.3 g, 0.636 mmol) and (2-ethyl-2H-[1,2,4]triazol-3-yl)methanol (97.3 mg, 1.2 molar eq; prepared as described in EP-A-170073) in DMF (10 ml) was added sodium hydride (30 mg of a 60% dispersion in mineral oil; 1.2 molar eq) and the mixture was stirred at room temperature for 1 h. Water (150 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-tert-Butyl-7-(2,5-difluorophenyl)-2-(2-ethyl-2H-[1,2,4]triazol-3-ylmethoxy)-4-methylpyrazolo[1,5-d][1,2,4]triazine was isolated as a gum, which solidified upon trituration under diethyl ether/isohexane (10 mg, mp=109° C.). 1H NMR (360 MHz, CDCl3) δ 1.40 (3H, t, J=7.3 Hz), 1.55 (9H, s), 3.08 (3H, s), 4.14 (2H, q, J=7.3 Hz), 5.48 (2H, s), 7.18-7.41 (3H, m), 7.88 (1H, s); MS (ES+) m/e 428 [MH]+.

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-e18b1e77ddec48989065b5fe85992dfa
Source dataset
uspto-grants-2005_03
Patent number
US06872720B2

Reaction notes

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