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

HRID 1045751Notes

Reaction equation

HRID 1045751 reaction equation
Br[C:2]1[N:7]2[CH:8]=[CH: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.[S:24]1[CH:28]=[CH:27][CH:26]=[C:25]1B(O)O.C([O-])([O-])=O.[Cs+].[Cs+]>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.CN(C=O)C>[S:24]1[CH:28]=[CH:27][CH:26]=[C:25]1[C:2]1[N:7]2[CH:8]=[CH: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

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 27339602-Thiopheneboronic acidHCID 10249304tert-Butyl 4-(5-bromoimidazo[1,2-a]pyrazin-8-yl)piperazine-1-carboxylate

Product 1

HCID 58447036tert-Butyl 4-(5-(thiophen-2-yl)imidazo[1,2-a]pyrazin-8-yl)piperazine-1-carboxylateYield 72%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

A 100 mL round bottom flask was charged with tert-butyl 4-(5-bromoimidazo[1,2-a]pyrazin-8-yl)piperazine-1-carboxylate (1.0 g, 2.62 mmol), thiophen-2-ylboronic acid (0.50 g, 3.93 mmol), Pd(PPh3)2Cl2 (200 mg, 0.26 mmol), Cs2CO3 (0.60 g, 3.93 mmol) and DMF (30 mL). After air was purged by bubbling N2 into the reaction solution, the reaction mixture was heated at 90° C. for 30 h. Work-up: the reaction mixture was poured into water (150 mL) and extracted with EtOAc (200 mL×3). The combined organic layers were dried over anhydrous Na2SO4 and then concentrated in vacuo. The residue was further purified by flash column chromatography on silica gel with 10% EtOAc in petroleum ether, to afford 0.70 g (72%) of the product as a yellow solid. MS m/z: 386 (M+H+).

Workup

  1. customAfter air was purged
  2. customby bubbling N2 into the reaction solution
  3. additionthe reaction mixture was poured into water (150 mL)
  4. extractionextracted with EtOAc (200 mL×3)
  5. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  6. concentrationconcentrated in vacuo
  7. customThe residue was further purified by flash column chromatography on silica gel with 10% EtOAc in petroleum ether

Sources & evidence

ORD record
ord-9249a64c31e341b9bacb3f4686670980
Source dataset
uspto-grants-2013_10
Patent number
US08569300B2

Reaction notes

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