Reaction #421654

Reaction equation

NaCNBH3

HOAc

5-bromopyridin-3-amine

acetone

→

5-bromo-N-isopropylpyridin-3-amine

Solvents

MeOH

Conditions

Workup

1. 1
   workup.STIRRINGstirred at room temperature overnight
2. 2
   OtherThe MeOH was removed under vacuum
3. 3
   Otherthe residue was partitioned between EtOAc and saturated aqueous NaHCO3
4. 4
   DryingThe organic layer was dried over MgSO4
5. 5
   Otherevaporated under vacuum
6. 6
   OtherThe crude product was purified on a silica gel column (100% hexane→90:10 hexane:EtOAc)

Procedure

To a solution of 5-bromopyridin-3-amine (XXV) (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 (XLVI) 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).

Source