Methanesulfonic Acid → 3-bromo-2-methyl-6-(1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-3-yl)pyridine

HRID 1047295Notes

Reaction equation

HRID 1047295 reaction equation
[Br:1][C:2]1[C:3]([CH3:13])=[N:4][C:5]([C:8]2[NH:12][CH:11]=[N:10][N:9]=2)=[CH:6][CH:7]=1.[O:14]1[CH:19]=[CH:18][CH2:17][CH2:16][CH2:15]1.CS(O)(=O)=O.C(N(CC)CC)C>O1CCCC1>[Br:1][C:2]1[C:3]([CH3:13])=[N:4][C:5]([C:8]2[N:12]=[CH:11][N:10]([CH:15]3[CH2:16][CH2:17][CH2:18][CH2:19][O:14]3)[N:9]=2)=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 6395Methanesulfonic AcidHCID 80803,4-dihydro-2H-pyranHCID 8471TriethylamineHCID 178432647HCID 178432647, compound

Product 1

HCID 582983093-bromo-2-methyl-6-(1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-3-yl)pyridineYield 80%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
68 °C

Procedure

3-Bromo-2-methyl-6-(4H-1,2,4-triazol-3-yl)pyridine (1 equiv), 3,4-dihydro-2H-pyran (2 equiv) and methanesulfonic acid (0.1 equiv) were combined in tetrahydrofuran, while stirring under nitrogen. The reaction was heated to 68° C. for 3.5 h. After cooling to room temperature over 1 h, triethylamine (0.4 equiv) was added and the resulting solution was stirred 10 min and then concentrated under reduced pressure. Acetonitrile was added and excess tetrahydrofuran was removed by codistillation under reduced pressure, with heating to 35° C. (twice). The resulting residue was dissolved in acetonitrile (1 volume) and water (2.25 volumes) was added. The resultant suspension was stirred 30 min. Solids were collected by filtration, washed with a solution of 20% acetonitrile in water and dried under reduced pressure. The crude product was triturated with hexanes, filtered, further washed with hexanes and dried in a vacuum oven at 35° C. to provide the desired product in 80% yield, as an off white solid. MS (ESI) m/z 324.9 [M+2]+.

Workup

  1. temperatureAfter cooling to room temperature over 1 h
  2. stirringthe resulting solution was stirred 10 min
  3. concentrationconcentrated under reduced pressure
  4. additionAcetonitrile was added
  5. customexcess tetrahydrofuran was removed by codistillation under reduced pressure
  6. temperaturewith heating to 35° C. (twice)
  7. dissolutionThe resulting residue was dissolved in acetonitrile (1 volume)
  8. additionwater (2.25 volumes) was added
  9. stirringThe resultant suspension was stirred 30 min
  10. filtrationSolids were collected by filtration
  11. washwashed with a solution of 20% acetonitrile in water
  12. customdried under reduced pressure
  13. customThe crude product was triturated with hexanes
  14. filtrationfiltered
  15. washfurther washed with hexanes
  16. customdried in a vacuum oven at 35° C.

Sources & evidence

ORD record
ord-7020e71fb79447e88b62db499b153772
Source dataset
uspto-grants-2013_10
Patent number
US08569494B2

Reaction notes

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