Potassium Acetate → 1-Methyl-5-(5-(oxetan-3-yl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)-6-oxo-1,6-dihydropyridin-3-ylboronic acid

HRID 1021784Notes

Reaction equation

HRID 1021784 reaction equation
Br[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:23]=[C:14]3[CH2:15][N:16]([CH:19]4[CH2:22][O:21][CH2:20]4)[CH2:17][CH2:18][N:13]3[N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1.CC1(C)C(C)(C)[O:28][B:27](B2OC(C)(C)C(C)(C)O2)[O:26]1.C([O-])(=O)C.[K+]>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>[CH3:8][N:6]1[C:5](=[O:9])[C:4]([NH:10][C:11]2[CH:23]=[C:14]3[CH2:15][N:16]([CH:19]4[CH2:22][O:21][CH2:20]4)[CH2:17][CH2:18][N:13]3[N:12]=2)=[CH:3][C:2]([B:27]([OH:28])[OH:26])=[CH:7]1

Participants

6

Reactant 3

HCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 580441695-bromo-1-methyl-3-(5-(oxetan-3-yl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)pyridin-2(1H)-one

Product 1

HCID 580443071-Methyl-5-(5-(oxetan-3-yl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)-6-oxo-1,6-dihydropyridin-3-ylboronic acidYield 33%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

A 100-mL round bottomed flask equipped with a magnetic stirrer was charged with 5-bromo-1-methyl-3-(5-(oxetan-3-yl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)pyridin-2(1H)-one 125i (1.0 g, 2.64 mmol), 4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bi(1,3,2-dioxaborolane) (2.0 g, 7.92 mmol), PdCl2(dppf) (190 mg, 0.26 mmol), potassium acetate (776 mg, 7.92 mmol), and dioxane (40 mL). After bubbling argon into the mixture for 30 minutes, a reflux condenser was attached to the flask and mixture was stirred at 100° C. for 6 h under an argon atmosphere. The resulting mixture was filtered and the filtrate was evaporated under reduced pressure. The residue was purified by reverse-phase Combiflash eluting with 0.3% NH4HCO3 water/CH3CN to afford 163a as a white solid (300 mg, 33%). MS: [M+H]+ 346.

Workup

  1. customA 100-mL round bottomed flask equipped with a magnetic stirrer
  2. customAfter bubbling argon into the mixture for 30 minutes
  3. customa reflux condenser was attached to the flask and mixture
  4. filtrationThe resulting mixture was filtered
  5. customthe filtrate was evaporated under reduced pressure
  6. customThe residue was purified by reverse-phase Combiflash
  7. washeluting with 0.3% NH4HCO3 water/CH3CN

Sources & evidence

ORD record
ord-11b637c137fe4a41aa9e0f9105204e7f
Source dataset
uspto-grants-2014_05
Patent number
US08716274B2

Reaction notes

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