Cesium carbonate → tert-Butyl 4-(5-(furan-3-yl)-[1,2,4]triazolo[4,3-a]pyrazin-8-yl)piperazine-1-carboxylate

HRID 1045710Notes

Reaction equation

HRID 1045710 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.[O:24]1[CH:28]=[CH:27][C:26](B(O)O)=[CH:25]1.C([O-])([O-])=O.[Cs+].[Cs+].O1CCOCC1>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.O>[O:24]1[CH:28]=[CH:27][C:26]([C:2]2[N:7]3[CH:8]=[N:9][N:10]=[C:6]3[C:5]([N:11]3[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]3)=[N:4][CH:3]=2)=[CH:25]1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 312751,4-DioxaneHCID 2734358Furan-3-boronic acidHCID 58447004Tert-butyl 4-(5-bromo-[1,2,4]triazolo[4,3-a]pyrazin-8-yl)piperazine-1-carboxylate

Product 1

HCID 58447023tert-Butyl 4-(5-(furan-3-yl)-[1,2,4]triazolo[4,3-a]pyrazin-8-yl)piperazine-1-carboxylateYield 97.3%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

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 (800 mg, 2.08 mmol), furan-3-ylboronic acid (349 mg, 3.12 mmol), Pd(PPh3)4 (240 mg, 0.312 mmol), Cs2CO3 (1.00 g, 3.12 mmol), 1,4-dioxane (11 mL) and water (4 mL). 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 0.75 g (97%) of the product as a yellow solid. MS m/z: 371 (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-8463c6b0fd0b4ab38940c8e72f8116c7
Source dataset
uspto-grants-2013_10
Patent number
US08569300B2

Reaction notes

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