1,4-Dioxane → 2-Cyclopropyl-1-(2-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenylamino)-6-((2,2,2-trifluoroethoxy)methyl)pyrimidin-4-yl)ethanol

HRID 59143Notes

Reaction equation

HRID 59143 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH:15][C:16]2[N:21]=[C:20]([CH:22]=[O:23])[CH:19]=[C:18]([CH2:24][O:25][CH2:26][C:27]([F:30])([F:29])[F:28])[N:17]=2)[CH:6]=[CH:7][C:8]=1[N:9]1[CH:13]=[C:12]([CH3:14])[N:11]=[CH:10]1.O1CCOCC1.[CH:37]1([CH2:40][Mg]Br)[CH2:39][CH2:38]1>C1COCC1>[CH:37]1([CH2:40][CH:22]([C:20]2[CH:19]=[C:18]([CH2:24][O:25][CH2:26][C:27]([F:29])([F:30])[F:28])[N:17]=[C:16]([NH:15][C:5]3[CH:6]=[CH:7][C:8]([N:9]4[CH:13]=[C:12]([CH3:14])[N:11]=[CH:10]4)=[C:3]([O:2][CH3:1])[CH:4]=3)[N:21]=2)[OH:23])[CH2:39][CH2:38]1

Participants

5

Reactant 3

HCID 312751,4-DioxaneHCID 1178240362-(3-Methoxy-4-(4-methyl-1H-imidazol-1-yl)phenylamino)-6-((2,2,2-trifluoroethoxy)methyl)-pyrimidine-4-carbaldehydeHCID 178419657HCID 178419657, compound

Product 1

HCID 863440662-Cyclopropyl-1-(2-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenylamino)-6-((2,2,2-trifluoroethoxy)methyl)pyrimidin-4-yl)ethanol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

2-(3-Methoxy-4-(4-methyl-1H-imidazol-1-yl)phenylamino)-6-((2,2,2-trifluoroethoxy)methyl)-pyrimidine-4-carbaldehyde (92 mg, 0.22 mmol) was coevaporated with dioxane and dissolved in THF (5 mL). The solution was cooled on an ice bath and (cyclopropylmethyl)magnesium bromide was added over 30 min. The mixture was quenched by addition of an ammonium chloride (aq, sat). The organic phase was separated and aquous phase was extracted with ethyl acetate (2×5 mL). The combined organic phase was dried over sodium sulfate and filtered through a short pad of silica. The solvents were removed and the residue was purified by preparative HPLC to give the title compound as a dry film 17 mg (16%).

Workup

  1. temperatureThe solution was cooled on an ice bath
  2. customThe mixture was quenched by addition of an ammonium chloride (aq, sat)
  3. customThe organic phase was separated
  4. extractionaquous phase was extracted with ethyl acetate (2×5 mL)
  5. dry with materialThe combined organic phase was dried over sodium sulfate
  6. filtrationfiltered through a short pad of silica
  7. customThe solvents were removed
  8. customthe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-9e29fce59b4743f2b3afea152abcf297
Source dataset
uspto-grants-2016_09
Patent number
US09439904B2

Reaction notes

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