Potassium Carbonate → HCID 89487095, compound

HRID 510175Notes

Reaction equation

HRID 510175 reaction equation
Br[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Br:8])[CH:7]=1.Cl.[NH2:10][C@H:11]([CH3:20])[C:12]([NH:14][CH2:15][C:16]([F:19])([F:18])[F:17])=[O:13].C(=O)([O-])[O-].[K+].[K+]>[Cu]I.CS(C)=O>[Br:8][C:6]1[CH:7]=[C:2]([NH:10][C@H:11]([CH3:20])[C:12]([NH:14][CH2:15][C:16]([F:17])([F:18])[F:19])=[O:13])[CH:3]=[N:4][CH:5]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 693693,5-DibromopyridineHCID 89487026HCID 89487026, compound

Product 1

HCID 89487095HCID 89487095, compoundYield 74.8%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
120 °C

Procedure

In a microwave vial equipped with a magnetic stirrer, 3,5-Dibromopyridine (Aldrich Chemical) (1 g, 4.22 mmol), (R)-2-amino-N-(2,2,2-trifluoroethyl)propanamide hydrochloride (0.872 g, 4.22 mmol), Potassium carbonate (2.334 g, 16.89 mmol) were added followed by DMSO (6.03 ml, 0.7M). The reaction mixture was stirred and purged under nitrogen for 10 minutes, then Copper (I) Iodide (0.08 g, 0.422 mmol) was added and the reaction mixture was heated in an oil bath at 120° C. for 2 hours. The cooled reaction mixture was then partitioned between Isopropanol (IPA): Chloroform (1:3) and Water, the aqueous layer was extracted with twice with IPA:Chloroform mixture. The combined organic layers were extracted with water, dried over anhydrous magnesium sulfate, filtered and concentrated to give the crude sample. Purification on silica (100 g SNAP Biotage column) using 0-5% Methanol/Dichloromethane gave (R)-2-(5-bromopyridin-3-ylamino)-N-(2,2,2-trifluoroethyl)propanamide, I-1, (1.03 g, 74.8% yield) LRMS (ESI) m/z 325.9 [(M+H)+; calcd for C10H11BrF3N3O: 326.01]

Workup

  1. customIn a microwave vial equipped with a magnetic stirrer
  2. custompurged under nitrogen for 10 minutes
  3. customThe cooled reaction mixture
  4. customwas then partitioned between Isopropanol (IPA)
  5. extractionChloroform (1:3) and Water, the aqueous layer was extracted with twice with IPA
  6. extractionThe combined organic layers were extracted with water
  7. dry with materialdried over anhydrous magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customto give the crude sample
  11. customPurification on silica (100 g SNAP Biotage column)

Sources & evidence

ORD record
ord-81f497aa251f4de2bd323b621b8464a0
Source dataset
uspto-grants-2015_08
Patent number
US09096598B2

Reaction notes

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