Nitrogen → 1-(4-(3-Bromoimidazo[1,2-b]pyridazin-6-yl)piperazin-1-yl)-3,3-dimethylbutan-1-one

HRID 870737Notes

Reaction equation

HRID 870737 reaction equation
N#N.[Br:3][C:4]1[N:8]2[N:9]=[C:10]([N:13]3[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]3)[CH:11]=[CH:12][C:7]2=[N:6][CH:5]=1.C1(N)C(F)=C(F)C(F)=C(N)C=1F.Cl.Cl.[CH3:33][C:34]([CH3:40])([CH3:39])[CH2:35][C:36](Cl)=[O:37].CCN(C(C)C)C(C)C>C(OCC)(=O)C>[Br:3][C:4]1[N:8]2[N:9]=[C:10]([N:13]3[CH2:14][CH2:15][N:16]([C:36](=[O:37])[CH2:35][C:34]([CH3:40])([CH3:39])[CH3:33])[CH2:17][CH2:18]3)[CH:11]=[CH:12][C:7]2=[N:6][CH:5]=1

Participants

7

Reactant 5

HCID 947NitrogenHCID 815143,3-Dimethylbutanoyl chlorideHCID 81531DiisopropylethylamineHCID 149026Tetrafluoro-m-phenylenediamine dihydrochlorideHCID 866964323-Bromo-6-piperazin-1-yl-imidazo[1,2-b]pyridazine

Product 1

HCID 866964461-(4-(3-Bromoimidazo[1,2-b]pyridazin-6-yl)piperazin-1-yl)-3,3-dimethylbutan-1-one

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a rapidly stirred, ambient temperature, N2 blanketed, suspension of 3-bromo-6-piperazin-1-yl-imidazo[1,2-b]pyridazine (dihydrochloride (400.5 mg, 1.1 mmol) and 3,3-dimethylbutanoyl chloride [7065-46-5] (0.2 mL, 1.4 mmol) in ethyl acetate (50 mL) was added Hunig's base [7087-68-5] (0.8 mL, 4.6 mmol) and the reaction allowed to stir over night. Once complete, the reaction was washed with brine, dried (MgSO4), and crystallized from chilled ethyl acetate/heptane to afford 392.5 mg of white crystalline powder, mp. 170-171° C. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.02 (s, 9H) 2.30 (s, 2H) 3.57 (d, J=7.06 Hz, 4H) 3.63-3.72 (m, 4H) 7.26 (d, J=9.92 Hz, 1H) 7.63 (s, 1H) 7.91 (d, J=9.92 Hz, 1H). 13C NMR (100 MHz, DMSO-d6) δ ppm 29.57, 30.81, 40.12, 43.50, 45.26, 45.34, 99.17, 110.56, 125.96, 131.44, 136.42, 154.89, 169.49. LRMS (ESI) m/z 380.1/382.1 [(M+H)]+, calc'd for C16H22BrN5O: 380.28.

Workup

  1. stirringto stir over night
  2. washOnce complete, the reaction was washed with brine
  3. dry with materialdried (MgSO4)
  4. customcrystallized
  5. temperaturefrom chilled ethyl acetate/heptane

Sources & evidence

ORD record
ord-d41493b453644ab8a3b153e81bac7fd8
Source dataset
uspto-grants-2015_03
Patent number
US08969565B2

Reaction notes

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