Methyl Ethyl Ketone → HCID 131735909, compound

HRID 2207404Notes

Reaction equation

HRID 2207404 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([NH2:8])=[N:6][CH:7]=1.[CH3:9][C:10](=O)[CH2:11][CH3:12].[Si]([C:18]#[N:19])(C)(C)C>C(#N)C.O.[Cl-].[Zn+2].[Cl-]>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][C:10]([CH3:9])([CH2:11][CH3:12])[C:18]#[N:19])=[N:6][CH:7]=1

Participants

7

Reactant 3

HCID 6569Methyl Ethyl KetoneHCID 706222-Amino-5-bromopyridineHCID 82115Trimethylsilyl cyanide

Product 1

HCID 131735909HCID 131735909, compound

Reagents, catalysts & solvents 3

HCID 3007855ZincchlorideCatalystHCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of 5-bromopyridin-2-amine (500 mg, 2.89 mmol), butan-2-one (611 μl, 6.82 mmol), and zinc chloride (0.5 M, 1.15 mL, 0.578 mmol) in acetonitrile (1.44 mL) was purged with Ar(g) for ˜5 minutes. The reaction was cooled to 0° C. and TMS-CN (775 μl, 5.78 mmol) was added dropwise. The reaction mixture was heated to 85° C. overnight. Upon cooling, the reaction mixture was diluted with water and extracted with dichloromethane (3×). The organic layer was concentrated under reduced pressure and the residue was purified by silica gel chromatography (ethyl acetate/hexanes) to yield 2-[(5-bromopyridin-2-yl)amino]-2-methylbutanenitrile. 1H NMR (500 MHz, CDCl3) δ 8.19 (d, J=3.2, 1H), 7.49 (dd, J=2.6, 8.9, 1H), 6.46 (d, J=9.6, 1H), 4.74 (s, 1H), 2.11-1.95 (m, 2H), 1.69 (s, 3H), 1.10-1.06 (m, 3H).

Workup

  1. customwas purged with Ar(g) for ˜5 minutes
  2. temperatureThe reaction mixture was heated to 85° C. overnight
  3. temperatureUpon cooling
  4. extractionextracted with dichloromethane (3×)
  5. concentrationThe organic layer was concentrated under reduced pressure
  6. customthe residue was purified by silica gel chromatography (ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-0fa2ab0ac1ad40c3ab07fa421e4af1f5
Source dataset
uspto-grants-2016_06
Patent number
US09376418B2

Reaction notes

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