2-Aminopyridine → HCID 58284795, compound

HRID 1963948Notes

Reaction equation

HRID 1963948 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][C:20]([CH3:24])([CH3:23])[CH2:19][O:18]1)(=O)=O.NC1C=CC=CN=1>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][C:20]([CH3:24])([CH3:23])[CH2:19][O:18]2)[CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 104392-AminopyridineHCID 24758Sodium hydrideHCID 3008092-Amino-6-bromopyridineHCID 86650641HCID 86650641, compound

Product 1

HCID 58284795HCID 58284795, compoundYield 46%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

6-Bromopyridin-2-amine (771 mg, 4.46 mmol) was dissolved in 10 mL of anhydrous DMF and cooled to 0° C. NaH (60% in mineral oil, 214 mg, 5.35 mmol) was added. After 10 min the solution was warmed to ambient temperature and stirred for 15 min until bubbling ceased, to give a dark green solution. (5,5-Dimethyl-1,4-dioxan-2-yl)methyl methanesulfonate (500 mg, 2.23 mmol) in 2 mL of DMF was added. After the addition was completed the solution was stirred at ambient temperature for 20 min, then heated at 60° C. for 1.5 hr. 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 a silica gel column (heptane:EtOAc 1:0 to 1:1) to give the product contaminated with the starting aminopyridine. Another purification on silica gel column (DCM:ether 20:1) gave the pure product (306 mg, 46%). LC-MS (m/z): 301.0/303.0 (M+H), retention time=0.89 min.

Workup

  1. temperatureAfter 10 min the solution was warmed to ambient temperature
  2. customuntil bubbling
  3. customto give a dark green solution
  4. additionAfter the addition
  5. stirringwas stirred at ambient temperature for 20 min
  6. temperatureheated at 60° C. for 1.5 hr
  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 a silica gel column (heptane:EtOAc 1:0 to 1:1)
  12. customto give the product
  13. customAnother purification on silica gel column (DCM:ether 20:1)

Sources & evidence

ORD record
ord-efe112a3e6b94c6f859d8bb37f63260d
Source dataset
uspto-grants-2013_04
Patent number
US08415381B2

Reaction notes

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