Methyl iodide → HCID 86267585, compound

HRID 718178Notes

Reaction equation

HRID 718178 reaction equation
[C:1]([C:5]1[NH:9][C:8](=[O:10])[N:7]([C:11]2[CH:16]=[CH:15][C:14]([O:17][C:18]3[CH:23]=[CH:22][N:21]=[C:20]([C:24]4[CH:25]=[N:26][N:27]([CH3:29])[CH:28]=4)[CH:19]=3)=[C:13]([CH3:30])[N:12]=2)[N:6]=1)([CH3:4])([CH3:3])[CH3:2].[C:31]([O-])([O-])=O.[Cs+].[Cs+].IC>CC(C)=O>[C:1]([C:5]1[N:9]([CH3:31])[C:8](=[O:10])[N:7]([C:11]2[CH:16]=[CH:15][C:14]([O:17][C:18]3[CH:23]=[CH:22][N:21]=[C:20]([C:24]4[CH:25]=[N:26][N:27]([CH3:29])[CH:28]=4)[CH:19]=3)=[C:13]([CH3:30])[N:12]=2)[N:6]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 10796Cesium carbonateHCID 136297934HCID 136297934, compound

Product 1

HCID 86267585HCID 86267585, compoundYield 47.7%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

A suspension of Example 7 (0.050 g, 0.12 mmol) in acetone (2.5 mL) was treated with Cs2CO3 (0.080 g, 0.25 mmol) and iodomethane (0.02 mL, 0.32 mmol) and the mixture was stirred at RT for 12 h. The solvent was removed in vacuo and the residue was dissolved in DCM (3 mL) and washed with water (3 mL). The aqueous phase was extracted with DCM (4×5 mL) and the combined organics were dried (MgSO4) and concentrated in in vacuo. The residue was triturated with Et2O (2 mL) and sonicated for 5 min, which lead to the precipitation of an off white solid. Solid was isolated by filtration and washed with Et2O (3×1 mL). The solid was dried under high vacuum for 3 h, and was then dissolved in MeCN and water, frozen to −78° C., and lyophilized to afford 3-(tert-butyl)-4-methyl-1-(6-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-1H-1,2,4-triazol-5(4H)-one (0.024 g, 46.4%) as an off white solid. 1H NMR (400 MHz, DMSO-d6): δ 8.37 (d, J=5.7 Hz, 1H), 8.26 (s, 1H), 7.96 (s, 1H), 7.85 (d, J=8.7 Hz, 1H), 7.72 (d, J=8.7 Hz, 1H), 7.20 (d, J=2.4 Hz, 1H), 6.65 (dd, J=5.7, 2.4 Hz, 1H), 3.84 (s, 3H), 3.39 (s, 3H), 2.34 (s, 3H), 1.37 (s, 9H); MS (ESI) m/z: 420.2 (M+H+).

Workup

  1. customThe solvent was removed in vacuo
  2. dissolutionthe residue was dissolved in DCM (3 mL)
  3. washwashed with water (3 mL)
  4. extractionThe aqueous phase was extracted with DCM (4×5 mL)
  5. dry with materialthe combined organics were dried (MgSO4)
  6. concentrationconcentrated in in vacuo
  7. customThe residue was triturated with Et2O (2 mL)
  8. customsonicated for 5 min
  9. customwhich lead to the precipitation of an off white solid
  10. customSolid was isolated by filtration
  11. washwashed with Et2O (3×1 mL)
  12. customThe solid was dried under high vacuum for 3 h
  13. dissolutionwas then dissolved in MeCN
  14. temperaturewater, frozen to −78° C.

Sources & evidence

ORD record
ord-59194cb9687d40d69a5acf9d88b23d11
Source dataset
uspto-grants-2015_11
Patent number
US09193719B2

Reaction notes

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