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

HRID 2200324Notes

Reaction equation

HRID 2200324 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)pyridine

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. The reaction was heated to 68° C. for 3.5 h, cooled to room temperature, and treated with triethylamine (0.4 equiv). The reaction mixture was concentrated under reduced pressure, treated with acetonitrile and concentrated under reduced pressure at 35° C. The residue was dissolved in acetonitrile (1 volume) and water (2.25 volumes), and the solids were collected by filtration, washed with a solution of 20% acetonitrile in water and dried. The crude product was triturated with hexanes, filtered, washed with hexanes and dried to provide the desired product, as a solid. MS (ESI) m/z 324.9 [M+2]+.

Workup

  1. temperaturecooled to room temperature
  2. concentrationThe reaction mixture was concentrated under reduced pressure
  3. additiontreated with acetonitrile
  4. concentrationconcentrated under reduced pressure at 35° C
  5. dissolutionThe residue was dissolved in acetonitrile (1 volume)
  6. filtrationwater (2.25 volumes), and the solids were collected by filtration
  7. washwashed with a solution of 20% acetonitrile in water
  8. customdried
  9. customThe crude product was triturated with hexanes
  10. filtrationfiltered
  11. washwashed with hexanes
  12. customdried

Sources & evidence

ORD record
ord-b05c784e2c7d43c8b6e0f70b3d2abbb8
Source dataset
uspto-grants-2016_06
Patent number
US09359364B2

Reaction notes

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