1,4-Dioxane → 2-(2-(3-Methoxy-4-(4-methyl-1H-imidazol-1-yl)phenylamino)-6-(1-(2,2,2-trifluoroethoxy)ethyl)pyrimidin-4-yl)propan-2-ol

HRID 59141Notes

Reaction equation

HRID 59141 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH:15][C:16]2[N:21]=[C:20]([C:22](=[O:24])[CH3:23])[CH:19]=[C:18]([CH:25]([O:27][CH2:28][C:29]([F:32])([F:31])[F:30])[CH3:26])[N:17]=2)[CH:6]=[CH:7][C:8]=1[N:9]1[CH:13]=[C:12]([CH3:14])[N:11]=[CH:10]1.O1CCOC[CH2:34]1.C[Mg]Br>C1COCC1>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH:15][C:16]2[N:21]=[C:20]([C:22]([OH:24])([CH3:34])[CH3:23])[CH:19]=[C:18]([CH:25]([O:27][CH2:28][C:29]([F:30])([F:31])[F:32])[CH3:26])[N:17]=2)[CH:6]=[CH:7][C:8]=1[N:9]1[CH:13]=[C:12]([CH3:14])[N:11]=[CH:10]1

Participants

5

Reactant 3

HCID 312751,4-DioxaneHCID 117824086HCID 117824086, compoundHCID 178418573HCID 178418573, compound

Product 1

HCID 863440692-(2-(3-Methoxy-4-(4-methyl-1H-imidazol-1-yl)phenylamino)-6-(1-(2,2,2-trifluoroethoxy)ethyl)pyrimidin-4-yl)propan-2-olYield 64%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

1-(2-(3-Methoxy-4-(4-methyl-1H-imidazol-1-yl)phenylamino)-6-(1-(2,2,2-trifluoroethoxy)-ethyl)pyrimidin-4-yl)ethanone (120 mg, 0.27 mmol) was coevaporated with dioxane and dissolved in THF (5 mL). The mixture was added slowly to a vigorously stirred solution of methylmagnesium bromide (0.712 mL of 3M solution, 2.14 mmol). The mixture was stirred for 10 minutes. The mixture was cooled in an ice bath and slowly quenched with a saturated solution of ammonium chloride in water (10 mL). The mixture was extracted with ethyl acetate (2×20 mL). The organic phase was separated, dried over sodium sulfate and concentrated. The residue was purified by preparative HPLC to give the title compound as a solid 81 mg (64%).

Workup

  1. temperatureThe mixture was cooled in an ice bath
  2. customslowly quenched with a saturated solution of ammonium chloride in water (10 mL)
  3. extractionThe mixture was extracted with ethyl acetate (2×20 mL)
  4. customThe organic phase was separated
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated
  7. customThe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-d7cf721f583f45b4baba100f76d757e4
Source dataset
uspto-grants-2016_09
Patent number
US09439904B2

Reaction notes

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