1,2-Dichloroethane → N-(5-bromo-6-methylpyridin-3-yl)-2-(2-cyanopropan-2-yl)isonicotinamide

HRID 594026Notes

Reaction equation

HRID 594026 reaction equation
C(Cl)CCl.[Br:5][C:6]1[CH:7]=[C:8]([NH2:13])[CH:9]=[N:10][C:11]=1[CH3:12].[C:14]([C:16]([C:19]1[CH:20]=[C:21]([CH:25]=[CH:26][N:27]=1)[C:22](O)=[O:23])([CH3:18])[CH3:17])#[N:15].C1C=NC2N(O)N=NC=2C=1>CN(C=O)C.O>[Br:5][C:6]1[CH:7]=[C:8]([NH:13][C:22](=[O:23])[C:21]2[CH:25]=[CH:26][N:27]=[C:19]([C:16]([C:14]#[N:15])([CH3:17])[CH3:18])[CH:20]=2)[CH:9]=[N:10][C:11]=1[CH3:12]

Participants

7

Reactant 4

HCID 111,2-Dichloroethane2×HCID 181649HOAt2×HCID 184588965-Bromo-6-methylpyridin-3-amineHCID 579297032-(2-Cyanopropan-2-yl)isonicotinic acid2×

Product 1

HCID 90409405N-(5-bromo-6-methylpyridin-3-yl)-2-(2-cyanopropan-2-yl)isonicotinamide

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolvent2×

Procedure

EDC (1.3 equiv.) was added to a solution of 5-bromo-6-methylpyridin-3-amine (1.05 equiv), 2-(2-cyanopropan-2-yl)isonicotinic acid (1.0 equiv), HOAt (1.3 equiv) in DMF (0.17 M). The mixture was stirred at ambient temperature 3 hrs. The reaction mixture was diluted with water and extracted with ethyl acetate. The combined extracts were washed sequentially with 1M aqueous sodium hydroxide and brine, dried over sodium sulfate, filtered, and concentrated. The crude was purified by ISCO(50% EtOAc/Heptane). Combined fractions still contained 17% 5-bromo-6-methylpyridin-3-amine. Add 2-(2-cyanopropan-2-yl)isonicotinic acid (0.3 equiv), EDC (0.3 equiv), HOAt (0.3 equiv) in DMF (0.17 M). After stirred at rt overnight, the reaction mixture was diluted with water and extracted with ethyl acetate. The combined extracts were washed sequentially with 1M aqueous sodium hydroxide and brine, dried over sodium sulfate, filtered, and concentrated to yield N-(5-bromo-6-methylpyridin-3-yl)-2-(2-cyanopropan-2-yl)isonicotinamide in 71% over three steps. LCMS (m/z) (M+H)=359.0, Rt=0.73 min.

Workup

  1. extractionextracted with ethyl acetate
  2. washThe combined extracts were washed sequentially with 1M aqueous sodium hydroxide and brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude was purified by ISCO(50% EtOAc/Heptane)
  7. stirringAfter stirred at rt overnight
  8. extractionextracted with ethyl acetate
  9. washThe combined extracts were washed sequentially with 1M aqueous sodium hydroxide and brine
  10. dry with materialdried over sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-d4fb9f36be944097931ea2af9ad74dbb
Source dataset
uspto-grants-2016_01
Patent number
US09242969B2

Reaction notes

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