Sodium hydride → HCID 58284662, compound

HRID 1623393Notes

Reaction equation

HRID 1623393 reaction equation
[Br:1][C:2]1[N:7]=[C:6]([NH2:8])[CH:5]=[CH:4][CH:3]=1.[H-].[Na+].CS(O[CH2:16][CH:17]1[CH2:22][O:21][CH2:20][C:19]([CH3:24])([CH3:23])[O:18]1)(=O)=O>CN(C=O)C.CCOC(C)=O>[Br:1][C:2]1[N:7]=[C:6]([NH:8][CH2:16][CH:17]2[CH2:22][O:21][CH2:20][C:19]([CH3:24])([CH3:23])[O:18]2)[CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 3008092-Amino-6-bromopyridineHCID 86650639HCID 86650639, compound

Product 1

HCID 58284662HCID 58284662, compoundYield 39%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

6-Bromopyridin-2-amine (722 mg, 4.17 mmol) was dissolved in 8 mL of anhydrous DMF and cooled to 0° C. NaH (60% in mineral oil, 195 mg, 4.87 mmol) was added. After 10 min the solution was warmed to ambient temperature and stirred for 45 min until bubbling ceased. The solution was cooled to 0° C. again and (6,6-dimethyl-1,4-dioxan-2-yl)methyl methanesulfonate (520 mg, 2.32 mmol) in 2 mL of DMF was added. After the addition was completed the solution was warmed to ambient temperature and stirred overnight. It was diluted with EtOAc and washed four times with water. The aqueous layers were combined and extracted once with EtOAc. The organic layers were combined, dried over Na2SO4 and concentrated. The resulting residue was purified on prep HPLC and the collected fractions were combined, concentrated, basified with Na2CO3 and extracted with EtOAc three times. The organic layers were combined, dried over Na2SO4 and concentrated to give the product as a light yellow oil (270 mg, 39%). LC-MS (m/z): 301.0/303.0 (M+H), retention time=0.86 min.

Workup

  1. temperatureAfter 10 min the solution was warmed to ambient temperature
  2. customuntil bubbling
  3. temperatureThe solution was cooled to 0° C. again
  4. additionAfter the addition
  5. temperaturewas warmed to ambient temperature
  6. stirringstirred overnight
  7. washwashed four times with water
  8. extractionextracted once with EtOAc
  9. dry with materialdried over Na2SO4
  10. concentrationconcentrated
  11. customThe resulting residue was purified on prep HPLC
  12. concentrationconcentrated
  13. extractionextracted with EtOAc three times
  14. dry with materialdried over Na2SO4
  15. concentrationconcentrated

Sources & evidence

ORD record
ord-363f87ffb1fe4e86826c9b03fb890923
Source dataset
uspto-grants-2014_07
Patent number
US08778951B2

Reaction notes

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