Triisopropyl borate → (6-(Butylamino)imidazo[1,2-b]pyridazin-3-yl)boronic acid
Reaction equation
Br[C:2]1[N:6]2[N:7]=[C:8]([NH:11][CH2:12][CH2:13][CH2:14][CH3:15])[CH:9]=[CH:10][C:5]2=[N:4][CH:3]=1.C([Li])CCC.C([O:24][B:25](OC(C)C)[O:26]C(C)C)(C)C>O1CCCC1>[CH2:12]([NH:11][C:8]1[CH:9]=[CH:10][C:5]2[N:6]([C:2]([B:25]([OH:26])[OH:24])=[CH:3][N:4]=2)[N:7]=1)[CH2:13][CH2:14][CH3:15]Participants
Conditions
- Temperature
- -78 °C
Procedure
A precooled (−78° C.) solution of 3-bromo-N-butylimidazo[1,2-b]pyridazin-6-amine (200 mg, 0.74 mmol) and tetrahydrofuran (4 mL) was treated dropwise with n-butyllithium (1.2 mL, 1.6 M, 1.9 mmol). The resulting reaction mixture was maintained at −78° C. for 5 min, then treated dropwise with tris(isopropyl)borate (0.21 mL, 0.89 mmol) and maintained at −78° C. for 2.5 h. The reaction was quenched with H2O (1 mL) and allowed to warm to RT. The organic volatiles were removed under reduced pressure, and the aqueous layer was acidified with 1 N HCl until a white precipitate formed. The solid was collected by filtration to afford (6-(butylamino)imidazo[1,2-b]pyridazin-3-yl)boronic acid (100 mg, 58%) as a white solid: 1H NMR (400 MHz, METHANOL-d4) δ ppm 7.56 (d, J=9.9 Hz, 1H), 7.39 (s, 1H), 6.66 (d, J=9.9 Hz, 1H), 3.25-3.35 (m, 2H), 1.60-1.75 (m, 1H), 1.37-1.58 (m, 1H), 0.94-1.08 (m, 1H); LCMS (ESI) m/e 235.2 [(M+H)+, calcd for C10H15BN4O2 235.1].
Workup
- customThe resulting reaction mixture
- temperaturemaintained at −78° C. for 2.5 h
- customThe reaction was quenched with H2O (1 mL)
- temperatureto warm to RT
- customThe organic volatiles were removed under reduced pressure
- customformed
- filtrationThe solid was collected by filtration
Sources & evidence
- ORD record
- ord-fd6468e81d7040999338305af7f8898b
- Source dataset
- uspto-grants-2015_03
- Patent number
- US08969565B2
Reaction notes
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