Cesium carbonate → 7-(2-Fluorophenyl)-2-(2-methyl-2H-[1,2,4]triazol-3-ylmethoxy)-3-[3-(trifluoromethyl)phenyl]pyrazolo[1,5-d][1,2,4]triazine

HRID 1016400Notes

Reaction equation

HRID 1016400 reaction equation
Br[C:2]1[C:3]([O:18][CH2:19][C:20]2[N:21]([CH3:25])[N:22]=[CH:23][N:24]=2)=[N:4][N:5]2[C:10]=1[CH:9]=[N:8][N:7]=[C:6]2[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[F:17].[F:26][C:27]([F:38])([F:37])[C:28]1[CH:29]=[C:30](B(O)O)[CH:31]=[CH:32][CH:33]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C(P(C(C)(C)C)C(C)(C)C)(C)(C)C>O1CCOCC1>[F:17][C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=1[C:6]1[N:5]2[N:4]=[C:3]([O:18][CH2:19][C:20]3[N:21]([CH3:25])[N:22]=[CH:23][N:24]=3)[C:2]([C:32]3[CH:31]=[CH:30][CH:29]=[C:28]([C:27]([F:38])([F:37])[F:26])[CH:33]=3)=[C:10]2[CH:9]=[N:8][N:7]=1

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 83681Tris(1,1-dimethylethyl)phosphineHCID 27343883-(Trifluoromethyl)phenylboronic acidHCID 184068533-Bromo-7-(2-fluorophenyl)-2-(2-methyl-2H-[1,2,4]triazol-3-ylmethoxy)pyrazolo[1,5-d][1,2,4]triazine

Product 1

HCID 184068407-(2-Fluorophenyl)-2-(2-methyl-2H-[1,2,4]triazol-3-ylmethoxy)-3-[3-(trifluoromethyl)phenyl]pyrazolo[1,5-d][1,2,4]triazineYield 81%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
90 °C

Procedure

A mixture of 3-bromo-7-(2-fluorophenyl)-2-(2-methyl-2H-[1,2,4]triazol-3-ylmethoxy)pyrazolo[1,5-d][1,2,4]triazine (60.2 mg, 0.149 mmol), 3-trifluoromethylbenzeneboronic acid (42.3 mg, 0.223 mmol) and cesium carbonate (96.9 mg, 0.297 mmol) in anhydrous 1,4-dioxane (5 ml) was degassed using three freeze-pump-thaw cycles. Tris(dibenzylideneacetone)palladium(0) (13.8 mg, 0.0151 mmol) and a 0.1 M solution of tri-tert-butylphosphine in 1,4-dioxane (0.357 ml, 0.357 mmol) was added, and the mixture was further degassed with two more freeze-pump-thaw cycles before heating at 90° C. under nitrogen for 17 h. The mixture was filtered through glass fibre paper, washing well with ethyl acetate (25 ml). The filtrate was washed with saturated aqueous NaCl (10 ml), and the aqueous layer was further extracted with ethyl acetate (25 ml). The combined organic extracts were dried (Na2SO4) and evaporated in vacuo. The residue was purified by flash chromatography (silica gel, 2% MeOH/CH2Cl2) to give 56.3 mg (81%) of the title compound as a yellow solid: mp=152-155° C. (EtOAc-isohexane); 1H NMR (360 MHz, CDCl3) δ 3.79 (3H, s), 5.58 (2H, s), 7.31 (1H, m), 7.41 (1H, td, J=7.6 and 0.9 Hz), 7.63-7.68 (3H, m), 7.80 (1H, m), 7.85-7.86 (2H, m), 7.93 (1H, s), 9.44 (1H, s); MS (ES+) m/e 470 [MH]+. Anal. Found C, 56.22; H, 3.35; N, 20.59%. C22H15F4N7O requires C, 56.29; H, 3.22; N, 20.89%.

Workup

  1. customwas degassed
  2. customthe mixture was further degassed with two more freeze-pump-thaw cycles
  3. filtrationThe mixture was filtered through glass fibre paper
  4. washwashing well with ethyl acetate (25 ml)
  5. washThe filtrate was washed with saturated aqueous NaCl (10 ml)
  6. extractionthe aqueous layer was further extracted with ethyl acetate (25 ml)
  7. dry with materialThe combined organic extracts were dried (Na2SO4)
  8. customevaporated in vacuo
  9. customThe residue was purified by flash chromatography (silica gel, 2% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-ee410693c28b48cba20ed075b0fe480e
Source dataset
uspto-grants-2002_11
Patent number
US06476030B1

Reaction notes

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