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

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).

1. stirringstirred at room temperature overnight
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)

ORD record

ord-a7f2e049b38e4e6e942c4577f3fa7ac1

Source dataset

uspto-grants-2016_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09233104B2