1,4-Dioxane → HCID 86684829, compound

HRID 1853130Notes

Reaction equation

HRID 1853130 reaction equation
[O:1]1CCO[CH2:3][CH2:2]1.Br[C:8]1[CH:9]=[N:10][C:11]([NH:14][C:15]([C:18]2[C:23]([Cl:24])=[CH:22][CH:21]=[CH:20][N:19]=2)([CH3:17])[CH3:16])=[N:12][CH:13]=1.C([Sn](CCCC)(CCCC)C(OCC)=C)CCC.C1C(=O)N([Br:50])C(=O)C1>C(OCC)(=O)C>[Br:50][CH2:3][C:2]([C:8]1[CH:9]=[N:10][C:11]([NH:14][C:15]([C:18]2[C:23]([Cl:24])=[CH:22][CH:21]=[CH:20][N:19]=2)([CH3:17])[CH3:16])=[N:12][CH:13]=1)=[O:1]

Participants

6

Reactant 4

HCID 312751,4-DioxaneHCID 67184N-bromobutanimideHCID 619414Stannane, tributyl(1-ethoxyethenyl)-HCID 67452850HCID 67452850, compound

Product 1

HCID 86684829HCID 86684829, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

To a stirring solution of dioxane (50 mL, degassed) was added 5-bromo-N-(2-(3-chloropyridin-2-yl)propan-2-yl)pyrimidin-2-amine (3.0 g, 12 mmol), Cl2Pd(PPh3)2 (0.65 g, 1.2 mmol), and tributyl(1 ethoxyvinyl)tin (2.66 mL, 13.8 mmol). The reaction was heated to 90° C. and stirred for 2 h. The reaction was then concentrated, followed by the addition of EtOAc (100 mL) and potassium fluoride (50 mL of a saturated aqueous solution). The mixture was stirred for 10 min and then filtered through a pad of celite. The filtrate was concentrated and then dissolved in THF (20 mL) and water (20 mL). NBS (4.9 g, 27.6 mmol) was then added, and the reaction was stirred for 20 min at rt. The reaction mixture was poured into ethyl acetate (200 mL), washed with saturated aqueous sodium bicarbonate (50 mL), dried over Na2SO4, filtered, concentrated, and purified by silica gel chromatography to afford 1.5 g of 2-bromo-1-(2-(2-(3-chloropyridin-2-yl)propan-2-ylamino)pyrimidin-5-yl)ethanone as a white powder.

Workup

  1. concentrationThe reaction was then concentrated
  2. additionfollowed by the addition of EtOAc (100 mL) and potassium fluoride (50 mL of a saturated aqueous solution)
  3. stirringThe mixture was stirred for 10 min
  4. filtrationfiltered through a pad of celite
  5. concentrationThe filtrate was concentrated
  6. dissolutiondissolved in THF (20 mL)
  7. stirringthe reaction was stirred for 20 min at rt
  8. washwashed with saturated aqueous sodium bicarbonate (50 mL)
  9. dry with materialdried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated
  12. custompurified by silica gel chromatography

Sources & evidence

ORD record
ord-f8d5de03304d4db5ae1bbd797a82d438
Source dataset
uspto-grants-2015_02
Patent number
US08962632B2

Reaction notes

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