Acetic Acid → 5-Bromo-N-(propan-2-yl)pyridin-3-amine

HRID 877121Notes

Reaction equation

HRID 877121 reaction equation
[NH2:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Br:8])[CH:7]=1.[CH3:9][C:10]([CH3:12])=O.CC(O)=O.[BH3-]C#N.[Na+]>CO>[Br:8][C:6]1[CH:7]=[C:2]([NH:1][CH:10]([CH3:12])[CH3:9])[CH:3]=[N:4][CH:5]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 180AcetoneHCID 8176813-Amino-5-bromopyridineHCID 5003444Sodium cyanoborohydride

Product 1

HCID 596129235-Bromo-N-(propan-2-yl)pyridin-3-amine

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 5-bromopyridin-3-amine (XXII) (535 mg, 3.09 mmol) in MeOH (62 mL) was added acetone (296 μL, 4.02 mL) The pH was adjusted to 4 using HOAc and stirred for 30 min NaCNBH3 (272 mg, 4.33 mmol) was added and stirred at room temperature overnight. The MeOH was removed under vacuum and the residue was partitioned between EtOAc and saturated aqueous NaHCO3. The organic layer was dried over MgSO4 and evaporated under vacuum. The crude product was purified on a silica gel column (100% hexane→90:10 hexane:EtOAc) to produce 5-bromo-N-isopropylpyridin-3-amine (XLIV) as an oil which slowly solidified into an off-white solid (309 mg, 1.44 mmol, 47% yield). 1H NMR (DMSO-d6, 500 MHz) δ ppm 1.12 (d, J=6.3 Hz, 6H), 3.55-3.59 (m, 1H), 6.03 (d, J=7.9 Hz, 1H), 7.05-7.06 (m, 1H), 7.75 (d, J=2 Hz, 1H), 7.90 (d, J=2 Hz, 1H); ESIMS found C8H11BrN2 m/z 215 (M+H).

Workup

  1. additionwas added
  2. customThe MeOH was removed under vacuum
  3. customthe residue was partitioned between EtOAc and saturated aqueous NaHCO3
  4. dry with materialThe organic layer was dried over MgSO4
  5. customevaporated under vacuum
  6. customThe crude product was purified on a silica gel column (100% hexane→90:10 hexane:EtOAc)

Sources & evidence

ORD record
ord-68ea7ca476b34ff08ec5725bfa84e190
Source dataset
uspto-grants-2015_03
Patent number
US08987298B2

Reaction notes

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