2-(Tributylstannyl)pyridine → 7-(2-Fluorophenyl)-2-(2-methyl-2H-[1,2,4]triazol-3-ylmethoxy)-3-(pyridin-2-yl)pyrazolo[1,5-d][1,2,4]triazine

HRID 1016410Notes

Reaction equation

HRID 1016410 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].C([Sn](CCCC)(CCCC)[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][N:32]=1)CCC>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cu]I>[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:31]3[CH:36]=[CH:35][CH:34]=[CH:33][N:32]=3)=[C:10]2[CH:9]=[N:8][N:7]=1

Participants

6

Reactant 2

HCID 6077842-(Tributylstannyl)pyridineHCID 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 184069147-(2-Fluorophenyl)-2-(2-methyl-2H-[1,2,4]triazol-3-ylmethoxy)-3-(pyridin-2-yl)pyrazolo[1,5-d][1,2,4]triazineYield 77%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °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 (81.8 mg, 0.202 mmol) and 2-(tributylstannyl)pyridine (0.1520 g, 0.413 mmol) in anhydrous 1,4-dioxane (8 ml) was degassed using three freeze-pump-thaw cycles. Tetrakis(triphenylphosphine)palladium(0) (32.5 mg, 0.0281 mmol) and copper(I) iodide (4.5 mg, 0.024 mmol) were added and the mixture was further degassed with one freeze-pump-thaw cycle before heating at 100° C. under nitrogen for 18 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 bar flash chromatography (silica gel, 4% MeOH/CH2Cl2 and silica gel, 0-4% MeOH/EtOAc) to give 62.4 mg (77%) of the title compound as a white solid, mp=186-187° C. (CH2Cl2-EtOAc); 1H NMR (400 MHz, CDCl3) δ 3.79 (3H, s), 5.61 (2H, s), 7.20 (1H, m), 7.29 (1H, t, J=9.4 Hz), 7.40 (1H, td, J=7.6 and 0.8 Hz), 7.64 (1H, mn), 7.73 (1H, td, J=7.8 and 1.8 Hz), 7.80 (1H, m), 7.89 (1H, s), 7.94 (1H, d, J=8.0 Hz), 8.70 (1H, m), 10.30 (1H, s); MS (ES+) m/e 403 [MH]+. Anal. Found C, 59.76; H, 3.65; N, 27.65%. C20H15FN8O requires C, 59.70; H, 3.76; N, 27.85%.

Workup

  1. customwas degassed
  2. customthe mixture was further degassed with one freeze-pump-thaw cycle
  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 bar flash chromatography (silica gel, 4% MeOH/CH2Cl2 and silica gel, 0-4% MeOH/EtOAc)

Sources & evidence

ORD record
ord-9418b033aafb405e9f6a0d6dd621ecae
Source dataset
uspto-grants-2002_11
Patent number
US06476030B1

Reaction notes

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