Cesium carbonate → 6-((2-((4-(trifluoromethoxy)phenyl)amino)pyrimidin-5-yl)methoxy)-3-((2-(trimethylsilyl)ethoxy)methyl)benzo[d]oxazol-2(3H)-one

HRID 77458Notes

Reaction equation

HRID 77458 reaction equation
[OH:1][C:2]1[CH:19]=[CH:18][C:5]2[N:6]([CH2:10][O:11][CH2:12][CH2:13][Si:14]([CH3:17])([CH3:16])[CH3:15])[C:7](=[O:9])[O:8][C:4]=2[CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].Cl[CH2:27][C:28]1[CH:29]=[N:30][C:31]([NH:34][C:35]2[CH:40]=[CH:39][C:38]([O:41][C:42]([F:45])([F:44])[F:43])=[CH:37][CH:36]=2)=[N:32][CH:33]=1>CN(C=O)C>[F:45][C:42]([F:43])([F:44])[O:41][C:38]1[CH:37]=[CH:36][C:35]([NH:34][C:31]2[N:30]=[CH:29][C:28]([CH2:27][O:1][C:2]3[CH:19]=[CH:18][C:5]4[N:6]([CH2:10][O:11][CH2:12][CH2:13][Si:14]([CH3:15])([CH3:16])[CH3:17])[C:7](=[O:9])[O:8][C:4]=4[CH:3]=3)=[CH:33][N:32]=2)=[CH:40][CH:39]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 866797425-(chloromethyl)-N-(4-(trifluoromethoxy)phenyl)pyrimidin-2-amineHCID 86679744HCID 86679744, compound

Product 1

HCID 866797456-((2-((4-(trifluoromethoxy)phenyl)amino)pyrimidin-5-yl)methoxy)-3-((2-(trimethylsilyl)ethoxy)methyl)benzo[d]oxazol-2(3H)-oneYield 39%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 6-hydroxy-3-((2-(trimethylsilyl)ethoxy)methyl)benzo[d]oxazol-2(3H)-one (0.093 g, 0.329 mmol) in DMF (4 mL) was add cesium carbonate (0.322 g, 0.988 mmol) and 5-(chloromethyl)-N-(4-(trifluoromethoxy)phenyl)pyrimidin-2-amine (0.1 g, 0.329 mmol). The reaction mixture was stirred at room temperature for 18 h. Solvent was removed under vacuum. The residue was dissolved in ethyl acetate, and washed with 10% NaOH solution, water, and brine. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated. The crude product was purified by flash chromatography on silica gel using 20 to 80% ethyl acetate in hexanes to give 6-((2-((4-(trifluoromethoxy)phenyl)amino)pyrimidin-5-yl)methoxy)-3-((2-(trimethylsilyl)ethoxy)methyl)benzo[d]oxazol-2(3H)-one as an white solid (0.07 g, 39%). LCMS: RT 2.216 min; 529.2 [M−H].

Workup

  1. customSolvent was removed under vacuum
  2. dissolutionThe residue was dissolved in ethyl acetate
  3. washwashed with 10% NaOH solution, water, and brine
  4. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product was purified by flash chromatography on silica gel using 20 to 80% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-d975a99e448f49cd8c4e88457209b2f9
Source dataset
uspto-grants-2014_09
Patent number
US08841301B2

Reaction notes

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