3-(4-bromo-2-fluoro-5-methylphenyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazole → 7-(5-Fluoro-2-methyl-4-(1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-3-yl)phenyl)-1-isopropyl-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

HRID 1890850Notes

Reaction equation

HRID 1890850 reaction equation
[CH:1]([N:4]1[C:9]2=[N:10][C:11]([Sn](C)(C)C)=[CH:12][N:13]=[C:8]2[NH:7][CH2:6][C:5]1=[O:18])([CH3:3])[CH3:2].Br[C:20]1[C:25]([CH3:26])=[CH:24][C:23]([C:27]2[N:31]=[CH:30][N:29]([CH:32]3[CH2:37][CH2:36][CH2:35][CH2:34][O:33]3)[N:28]=2)=[C:22]([F:38])[CH:21]=1>CN(C)C=O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[F:38][C:22]1[C:23]([C:27]2[N:31]=[CH:30][N:29]([CH:32]3[CH2:37][CH2:36][CH2:35][CH2:34][O:33]3)[N:28]=2)=[CH:24][C:25]([CH3:26])=[C:20]([C:11]2[N:10]=[C:9]3[N:4]([CH:1]([CH3:3])[CH3:2])[C:5](=[O:18])[CH2:6][NH:7][C:8]3=[N:13][CH:12]=2)[CH:21]=1

Participants

5

Reactant 2

HCID 666072813-(4-bromo-2-fluoro-5-methylphenyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazoleHCID 666080081-Isopropyl-7-(trimethylstannyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

Product 1

HCID 666075107-(5-Fluoro-2-methyl-4-(1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-3-yl)phenyl)-1-isopropyl-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-oneYield 52.7%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
140 °C

Procedure

1-Isopropyl-7-(trimethylstannyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one (300 mg, 0.84 mmol), 3-(4-bromo-2-fluoro-5-methylphenyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazole (428 mg, 1.26 mmol) and bis(triphenylphosphine)palladium(II) dichloride (56 mg, 0.08 mmol) were combined in N,N-dimethylformamide (5 mL). The mixture was degassed and heated at 140° C. under nitrogen for 3 h. After being cooled to room temperature, the reaction mixture was filtered and the filtrate was partitioned between ethyl acetate (15 mL) and water (15 mL). The organic layer was separated and the aqueous layer was extracted with ethyl acetate (10 mL×2). The combined organic layer was dried over sodium sulfate, filtered, concentrated under reduced pressure and purified by preparative TLC (15% methanol in dichloromethane) to give the title compound (200 mg, yield 52%) as a solid.

Workup

  1. customThe mixture was degassed
  2. temperatureAfter being cooled to room temperature
  3. filtrationthe reaction mixture was filtered
  4. customthe filtrate was partitioned between ethyl acetate (15 mL) and water (15 mL)
  5. customThe organic layer was separated
  6. extractionthe aqueous layer was extracted with ethyl acetate (10 mL×2)
  7. dry with materialThe combined organic layer was dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. custompurified by preparative TLC (15% methanol in dichloromethane)

Sources & evidence

ORD record
ord-300e9735495a4b03ac8800801a7d2d7d
Source dataset
uspto-grants-2013_08
Patent number
US08507492B2

Reaction notes

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