Potassium Carbonate → Tert-butyl 4-(5-isopentyl-[1,2,4]triazolo[4,3-a]pyrazin-8-yl)piperazine-1-carboxylate

HRID 1045713Notes

Reaction equation

HRID 1045713 reaction equation
Br[C:2]1[N:7]2[CH:8]=[N:9][N:10]=[C:6]2[C:5]([N:11]2[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]2)=[N:4][CH:3]=1.[CH2:24](B(O)O)[CH2:25][CH:26]([CH3:28])[CH3:27].C([O-])([O-])=O.[K+].[K+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1(C)C=CC=CC=1>[CH2:24]([C:2]1[N:7]2[CH:8]=[N:9][N:10]=[C:6]2[C:5]([N:11]2[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]2)=[N:4][CH:3]=1)[CH2:25][CH:26]([CH3:28])[CH3:27]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 15061386(3-Methylbutyl)boronic acidHCID 58447004Tert-butyl 4-(5-bromo-[1,2,4]triazolo[4,3-a]pyrazin-8-yl)piperazine-1-carboxylate

Product 1

HCID 67393351Tert-butyl 4-(5-isopentyl-[1,2,4]triazolo[4,3-a]pyrazin-8-yl)piperazine-1-carboxylateYield 44%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

A 50 mL round bottom flask was charged with tert-butyl 4-(5-bromo-[1,2,4]triazolo[4,3-a]pyrazin-8-yl)piperazine-1-carboxylate (1.0 g, 2.61 mmol), isopentylboronic acid (484 mg, 4.18 mmol), Pd(PPh3)4 (300 mg, 0.261 mmol), 2 M aqueous K2CO3 (2.6 mL, 5.2 mmol) and toluene (15 mL) under N2. The resulting mixture was heated under N2 at 100° C. overnight. Work-up: the reaction mixture was filtered. The filter cake was washed with EtOAc (10 mL) and the filtrate was extracted with more EtOAc (10 mL×3). The combined organic solutions were washed with brine, dried over anhydrous Na2SO4, and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel with 2% methanol in dichloromethane, to afford 0.43 g (44%) of tert-butyl 4-(5-isopentyl-[1,2,4]triazolo[4,3-a]pyrazin-8-yl)piperazine-1-carboxylate as a yellow solid. MS m/z: 375 (M+H+).

Workup

  1. filtrationthe reaction mixture was filtered
  2. washThe filter cake was washed with EtOAc (10 mL)
  3. extractionthe filtrate was extracted with more EtOAc (10 mL×3)
  4. washThe combined organic solutions were washed with brine
  5. dry with materialdried over anhydrous Na2SO4
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash column chromatography on silica gel with 2% methanol in dichloromethane

Sources & evidence

ORD record
ord-016af2443c57481ab0fcbf70e68e73be
Source dataset
uspto-grants-2013_10
Patent number
US08569300B2

Reaction notes

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