Cesium carbonate → (3-Bromo-imidazo[1,2-b]pyridazin-6-yl)-(tetrahydropyran-4-yl)-amine

HRID 870629Notes

Reaction equation

[Br:1][C:2]1[N:6]2[N:7]=[C:8](F)[CH:9]=[CH:10][C:5]2=[N:4][CH:3]=1.[O:12]1[CH2:17][CH2:16][CH:15]([NH2:18])[CH2:14][CH2:13]1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C>[Br:1][C:2]1[N:6]2[N:7]=[C:8]([NH:18][CH:15]3[CH2:16][CH2:17][O:12][CH2:13][CH2:14]3)[CH:9]=[CH:10][C:5]2=[N:4][CH:3]=1

Participants

Conditions

Temperature: 40 °C

Procedure

A mixture of 3-bromo-6-fluoroimidazo[1,2-b]pyridazine (1.4 g, 6.6 mmol), tetrahydro-2H-pyran-4-amine (1.0 g, 9.9 mmol), cesium carbonate (4.3 g, 13 mmol), and DMF (10 mL) was maintained at 40° C. for 16 h, then cooled to RT and partitioned between ethyl acetate (100 mL) and H2O (100 mL). The layers were separated, and the aqueous layer was extracted with ethyl acetate (4×40 mL). The combined organic layers were washed with H2O (100 mL) and brine (100 mL), then dried (MgSO4), filtered and concentrated to afford a residue that was purified by flash chromatography (SiO2) to afford 3-bromo-N-(tetrahydro-pyran-4-yl)imidazo[1,2-b]pyridazin-6-amine (1.6 g, 80%) as a light yellow solid: 1H NMR (400 MHz, MeOD-d4) δ 7.58 (d, J=9.9 Hz, 1H), 7.42 (s, 2H), 6.71 (d, J=9.9 Hz, 1H), 3.95-4.08 (m, 3H), 3.60 (td, J=11.5, 2.3 Hz, 2H), 2.16 (d, J=11.5 Hz, 2H), 1.53-1.69 (m, 2H); LCMS (ESI) m/e 297.1 [(M+H)+, calcd for C11H13BrN4O 297.0].

Workup

temperaturecooled to RT
custompartitioned between ethyl acetate (100 mL) and H2O (100 mL)
customThe layers were separated
extractionthe aqueous layer was extracted with ethyl acetate (4×40 mL)
washThe combined organic layers were washed with H2O (100 mL) and brine (100 mL)
dry with materialdried (MgSO4)
filtrationfiltered
concentrationconcentrated
customto afford a residue that
customwas purified by flash chromatography (SiO2)

Sources & evidence

ORD record: ord-9c790a6c273944789534cea966655f68
Source dataset: uspto-grants-2015_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08969565B2

Reaction notes

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