Cesium fluoride → 2-((trans)-2-(6-(3,5-dimethyl-1H-1,2,4-triazol-1-yl)-2-methylpyrimidin-4-yl)cyclopropyl)-3-vinylimidazo[1,2-a]pyridine

HRID 2199855Notes

Reaction equation

HRID 2199855 reaction equation
[CH3:1][C:2]1[N:6]=[C:5]([CH3:7])[N:4]([C:8]2[N:13]=[C:12]([CH3:14])[N:11]=[C:10]([C@@H:15]3[CH2:17][C@H:16]3[C:18]3[N:19]=[C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][N:21]4[C:26]=3I)[CH:9]=2)[N:3]=1.[F-].[Cs+].[CH2:30]([Sn](CCCC)(CCCC)C=C)[CH2:31]CC>CCOC(C)=O>[CH3:1][C:2]1[N:6]=[C:5]([CH3:7])[N:4]([C:8]2[N:13]=[C:12]([CH3:14])[N:11]=[C:10]([C@@H:15]3[CH2:17][C@H:16]3[C:18]3[N:19]=[C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][N:21]4[C:26]=3[CH:30]=[CH2:31])[CH:9]=2)[N:3]=1

Participants

5

Reactant 3

HCID 25953Cesium fluorideHCID 81998TributylvinyltinHCID 760714242-((trans)-2-(6-(3,5-dimethyl-1H-1,2,4-triazol-1-yl)-2-methylpyrimidin-4-yl)cyclopropyl)-3-iodoimidazo[1,2-a]pyridine

Product 1

HCID 760714252-((trans)-2-(6-(3,5-dimethyl-1H-1,2,4-triazol-1-yl)-2-methylpyrimidin-4-yl)cyclopropyl)-3-vinylimidazo[1,2-a]pyridine

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To Example 8 (0.11 g, 0.23 mmol), cesium fluoride (0.14 g, 0.93 mmol) and bis(tri-t-butylphosphine)palladium(O) (18 mg, 0.04 mmol) under nitrogen was added degassed dioxane (2.3 mL) followed by tributyl(vinyl)stannane (0.30 mg, 0.93 mmol). The reaction was heated at 80° C. for 2 h and, after cooling to room temperature, was diluted with EtOAc (10 mL). The organic layer was washed with saturated aqueous sodium carbonate (2×10 mL), dried over sodium sulfate, filtered and concentrated in vacuo. The crude material was purified by silica gel chromatography (0-100% EtOAc/hexanes) to give Example 10. 1H NMR (500 MHz, CDCl3) δ 8.17 (d, J=7.0 Hz, 1H), 7.60 (s, 1H), 7.55 (d, J=9.2 Hz, 1H), 7.21-7.17 (m, 1H), 6.93-6.82 (m, 2H), 5.63 (d, J=18.1 Hz, 1H), 5.43 (d, J=12.1 Hz, 1H), 2.93-2.87 (m, 1H), 2.89 (s, 3H), 2.74-2.70 (m, 1H), 2.67 (s, 3H), 2.39 (s, 3H), 2.00-1.92 (m, 2H) ppm; MS: m/z=372.3 (M+H).

Workup

  1. customdegassed dioxane (2.3 mL)
  2. temperatureafter cooling to room temperature
  3. washThe organic layer was washed with saturated aqueous sodium carbonate (2×10 mL)
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude material was purified by silica gel chromatography (0-100% EtOAc/hexanes)
  8. customto give Example 10

Sources & evidence

ORD record
ord-c4c4b3b9998f4ea5894300bf3259bbd7
Source dataset
uspto-grants-2016_06
Patent number
US09359348B2

Reaction notes

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