Sodium Carbonate → HCID 118126889, compound

HRID 1482880Notes

Reaction equation

HRID 1482880 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([NH:17][C:18]2[N:23]=[C:22]([C:24]([F:27])([F:26])[F:25])[CH:21]=[CH:20][N:19]=2)[CH:5]=[C:6](B2OC(C)(C)C(C)(C)O2)[CH:7]=1.Br[C:29]1[CH:30]=[N:31][C:32]([O:35][CH:36]2[CH2:41][CH2:40][CH:39]([C:42]([O:44][CH2:45][CH3:46])=[O:43])[CH2:38][CH2:37]2)=[N:33][CH:34]=1.O1CCOCC1.C(=O)([O-])[O-].[Na+].[Na+]>C(OCC)(=O)C.C(=O)(O)[O-].[Na+].O>[CH3:1][C:2]1[CH:7]=[C:6]([C:29]2[CH:30]=[N:31][C:32]([O:35][CH:36]3[CH2:41][CH2:40][CH:39]([C:42]([O:44][CH2:45][CH3:46])=[O:43])[CH2:38][CH2:37]3)=[N:33][CH:34]=2)[CH:5]=[C:4]([NH:17][C:18]2[N:23]=[C:22]([C:24]([F:27])([F:25])[F:26])[CH:21]=[CH:20][N:19]=2)[CH:3]=1

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 312751,4-DioxaneHCID 58456089N-(3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-4-(trifluoromethyl)pyrimidin-2-amineHCID 89582057HCID 89582057, compound

Product 1

HCID 118126889HCID 118126889, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
160 °C

Procedure

A suspension of N-[3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-4-(trifluoromethyl)pyrimidin-2-amine (150 mg, 0.396 mmol), ethyl 4-[(5-bromopyrimidin-2-yl)oxy]cyclohexanecarboxylate (130 mg, 0.396 mmol), 1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (0.026 g, 0.032 mmol), 1,4-dioxane (3.6 mL), water (0.36 mL), and aqueous sodium carbonate (2 M, 0.396 mL, 0.791 mmol) was placed under an argon atmosphere by performing 6 vacuum/argon cycles. The reaction mixture was then heated to 160° C. for 10 minutes using a microwave reactor. The resulting suspension was diluted with ethyl acetate (30 mL) and saturated aqueous sodium bicarbonate solution (15 mL). The layers were separated, and the organic layer was washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by chromatography on silica gel (ethyl acetate/hexanes) to afford ethyl 4-{[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyrimidin-2-yl]oxy}cyclohexanecarboxylate as a mixture of cis and trans isomers. MS ESI calc'd. for C25H27F3N5O3 [M+H]+ 502. found 502.

Workup

  1. customThe layers were separated
  2. washthe organic layer was washed with brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by chromatography on silica gel (ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-e559088fbe3842d8b469a7c412dbe117
Source dataset
uspto-grants-2016_08
Patent number
US09416111B2

Reaction notes

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