Cesium fluoride → HCID 68326551, compound

HRID 631843Notes

Reaction equation

HRID 631843 reaction equation
[CH2:1]([C:8]1[C:9](=[O:16])[NH:10][C:11](=[O:15])[NH:12][C:13]=1Cl)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC1(C)C(C)(C)OB([C:25]2[CH2:30][CH2:29][CH:28]([C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)[CH2:27][CH:26]=2)O1.[F-].[Cs+]>O1CCOCC1.O.[Cl-].[NH4+]>[CH2:1]([C:8]1[C:9](=[O:16])[NH:10][C:11](=[O:15])[NH:12][C:13]=1[C:34]1[CH2:35][CH2:36][CH:31]([C:28]2[CH:27]=[CH:26][CH:25]=[CH:30][CH:29]=2)[CH2:32][CH:33]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 3

HCID 25953Cesium fluorideHCID 112890924,4,5,5-Tetramethyl-2-([1,2,3,6-tetrahydro[1,1'-biphenyl]]-4-yl)-1,3,2-dioxaborolaneHCID 23648513HCID 23648513, compound

Product 1

HCID 68326551HCID 68326551, compoundYield 31.7%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 25517Ammonium ChlorideSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
140 °C

Procedure

A mixture of 5-benzyl-6-chloro-1H-pyrimidine-2,4-dione (WO006014394) (1.0 g), 4,4,5,5-tetramethyl-2-(4-phenylcyclohex-1-enyl)-[1,3,2]dioxaborolane (1.4 g), bis[di-tert-butyl(4-dimethylaminophenyl)phosphine]dichloropalladium(II) (0.06 g) and cesium fluoride (1.92 g) in 1,4-dioxane (18 mL) and water (2 mL) was heated at 140° C. in a microwave reactor for 20 minutes. The resulting mixture was diluted with saturated aqueous ammonium chloride and filtered to remove the precipitate. The filtrate was extracted with dichloromethane and the combined organic layers washed with water and brine, then dried over sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by column chromatography on silica gel, eluting with a mixture of methanol and dichloromethane (0:1 to 1:20 by volume) to afford the title compound 2a as an off-white solid (0.48 g). LCMS (Method A): Rt=3.56 min. (M+H)+=359. 1H NMR (DMSO-D6): δ 11.06 (1H, s), 10.69 (1H, s), 7.23-7.21 (10H, m), 5.84-5.79 (1H, m), 3.61 (2H, s), 3.57 (1H, s), 2.77-2.67 (1H, m), 2.19-2.16 (3H, m), 1.84-1.81 (1H, m), 1.68-1.67 (1H, m).

Workup

  1. filtrationfiltered
  2. customto remove the precipitate
  3. extractionThe filtrate was extracted with dichloromethane
  4. washthe combined organic layers washed with water and brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe resulting residue was purified by column chromatography on silica gel
  8. washeluting with a mixture of methanol and dichloromethane (0:1 to 1:20 by volume)

Sources & evidence

ORD record
ord-e3edab9a7f684295a0889f6e1ab4f621
Source dataset
uspto-grants-2016_04
Patent number
US09321736B2

Reaction notes

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