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

HRID 870631Notes

Reaction equation

HRID 870631 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.[CH:12]1([NH2:18])[CH2:17][CH2:16]C[CH2:14][CH2:13]1.C(=O)([O-])[O-:20].[Cs+].[Cs+]>CN(C=O)C>[Br:1][C:2]1[N:6]2[N:7]=[C:8]([NH:18][CH:12]3[CH2:17][CH2:16][O:20][CH2:14][CH2:13]3)[CH:9]=[CH:10][C:5]2=[N:4][CH:3]=1

Participants

5

Reactant 3

HCID 7965CyclohexylamineHCID 10796Cesium carbonateHCID 866963183-Bromo-6-fluoroimidazo[1,2-b]pyridazine

Product 1

HCID 25103082(3-Bromo-imidazo[1,2-b]pyridazin-6-yl)-(tetrahydropyran-4-yl)-amineYield 74%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
40 °C

Procedure

A mixture of 3-bromo-6-fluoroimidazo[1,2-b]pyridazine (1.1 g, 5.0 mmol), cyclohexylamine (0.86 mL, 7.5 mmol), cesium carbonate (3.3 g, 10 mmol), and DMF (10 mL) was maintained at 40° C. for 6 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 (1.1 g, 73%) as a light yellow solid: 1H NMR (400 MHz, MeOD) δ 7.53 (d, J=9.6 Hz, 1H), 7.39 (s, 1H), 6.68 (d, J=9.9 Hz, 1H), 3.68-3.87 (m, 1H), 2.14 (dd, J=12.6, 3.3 Hz, 2H), 1.82 (dt, J=13.3, 3.7 Hz, 2H), 1.70 (dt, J=12.8, 3.7 Hz, 1H), 1.38-1.52 (m, 2H), 1.23-1.38 (m, 3H); LCMS (ESI) m/e 295.2 [(M+H)+, calcd for C12H15BrN4 295.1].

Workup

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

Sources & evidence

ORD record
ord-824f08df3ffd418cad29403a1d3a4331
Source dataset
uspto-grants-2015_03
Patent number
US08969565B2

Reaction notes

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