Cesium carbonate → 6-(Imidazo[1,2-a]pyridin-7-ylamino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-ylboronic Acid

HRID 1021839Notes

Reaction equation

HRID 1021839 reaction equation
Br[C:2]1[N:3]=[C:4]([NH:10][C:11]2[CH:16]=[CH:15][N:14]3[CH:17]=[CH:18][N:19]=[C:13]3[CH:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1.CC1(C)C(C)(C)[O:24][B:23](B2OC(C)(C)C(C)(C)O2)[O:22]1.C([O-])([O-])=O.[Cs+].[Cs+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O1CCOCC1>[N:19]1[CH:18]=[CH:17][N:14]2[CH:15]=[CH:16][C:11]([NH:10][C:4]3[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=[C:2]([B:23]([OH:24])[OH:22])[N:3]=3)=[CH:12][C:13]=12

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 2733548Bis(pinacolato)diboraneHCID 866843315-Bromo-3-(imidazo[1,2-a]pyridin-7-ylamino)-1-methylpyrazin-2(1H)-one

Product 1

HCID 866843326-(Imidazo[1,2-a]pyridin-7-ylamino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-ylboronic AcidYield 70.5%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

A 100-mL round-bottomed flask equipped with a reflux condenser was charged with 185a (638 mg, 1.99 mmol), 4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bi(1,3,2-dioxaborolane) (Pin2B2, 2.54 mg, 10 mmol), 1,1′-bis(diphenylphosphino)ferrocenedichloropalladium(II) (163 mg, 0.18 mmol), Cs2CO3 (1.3 g, 3.98 mmol), and 1,4-dioxane (20 mL). After bubbling nitrogen through the mixture for 30 minutes, it was heated at 80° C. under nitrogen atmosphere for 3 h. The reaction mixture was cooled to room temperature and filtered. The filtrate was diluted with petroleum ether (150 mL) and ethyl acetate (15 mL). The resulting suspension was stirred at room temperature for 30 minutes. The solid was collected by filtration and further purified by silica-gel column chromatography eluting with dichloromethane/methanol (60/1 to 15/1) to afford 185b (400 mg, 70%) as an off-white solid. MS-ESI: [M+H]+ 286

Workup

  1. customA 100-mL round-bottomed flask equipped with a reflux condenser
  2. customAfter bubbling nitrogen through the mixture for 30 minutes
  3. temperatureThe reaction mixture was cooled to room temperature
  4. filtrationfiltered
  5. additionThe filtrate was diluted with petroleum ether (150 mL) and ethyl acetate (15 mL)
  6. filtrationThe solid was collected by filtration
  7. customfurther purified by silica-gel column chromatography
  8. washeluting with dichloromethane/methanol (60/1 to 15/1)

Sources & evidence

ORD record
ord-67295517d2ab4bad80e857e8b3d2702c
Source dataset
uspto-grants-2014_05
Patent number
US08716274B2

Reaction notes

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