Potassium Carbonate → 3-(6-(aminomethyl)pyridin-3-yl)-N-butylimidazo[1,2-b]pyridazin-6-amine acetic acid salt

HRID 870670Notes

Reaction equation

HRID 870670 reaction equation
[CH2:1]([NH:5][C:6]1[CH:7]=[CH:8][C:9]2[N:10]([C:12](B(O)O)=[CH:13][N:14]=2)[N:11]=1)[CH2:2][CH2:3][CH3:4].Br[C:19]1[CH:20]=[CH:21][C:22]([CH2:25][NH2:26])=[N:23][CH:24]=1.[C:27](=[O:30])([O-])[O-:28].[K+].[K+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(#N)C.O>[C:27]([OH:28])(=[O:30])[CH3:1].[NH2:26][CH2:25][C:22]1[N:23]=[CH:24][C:19]([C:12]2[N:10]3[N:11]=[C:6]([NH:5][CH2:1][CH2:2][CH2:3][CH3:4])[CH:7]=[CH:8][C:9]3=[N:14][CH:13]=2)=[CH:20][CH:21]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 49761678(5-Bromopyridin-2-yl)methanamineHCID 86696352(6-(Butylamino)imidazo[1,2-b]pyridazin-3-yl)boronic acid

Product 1

HCID 866963723-(6-(aminomethyl)pyridin-3-yl)-N-butylimidazo[1,2-b]pyridazin-6-amine acetic acid saltYield 48.6%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 18373917Acetonitrile--water (1/1)Solvent

Conditions

Temperature
145 °C

Procedure

To a mixture of (6-(butylamino)imidazo[1,2-b]pyridazin-3-yl)boronic acid (36 mg, 0.15 mmol), (5-bromopyridin-2-yl)methanamine (35 mg, 0.18 mmol), [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium(II) (5 mg, 0.01 mmol) and potassium carbonate (31 mg, 0.23 mmol) was added 3:1 acetonitrile/water (3 mL). The resulting mixture was heated at 145° C. (microwave) for 800 s. The reaction was then filtered and concentrated. The residue was dissolved in methanol, and then filtered again. The filtration was finally purified by preparative HPLC to afford 3-(6-(aminomethyl)pyridin-3-yl)-N-butylimidazo[1,2-b]pyridazin-6-amine acetic acid salt (13 mg, 29% yield) as a white solid: 1H NMR (METHANOL-d4) δ: 8.64 (d, J=8.3 Hz, 1H), 7.91 (s, 1H), 7.66 (d, J=9.6 Hz, 1H), 6.77 (d, J=9.9 Hz, 1H), 3.39 (t, J=7.1 Hz, 2H), 1.94 (s, 4H), 1.71 (t, J=7.3 Hz, 2H), 1.41-1.58 (m, 2H), 1.01 (t, J=7.5 Hz, 3H); LRMS (ESI) m/e 297.4 [(M+H)+, calcd for C16H21N6, 297.2].

Workup

  1. filtrationThe reaction was then filtered
  2. concentrationconcentrated
  3. dissolutionThe residue was dissolved in methanol
  4. filtrationfiltered again
  5. filtrationThe filtration
  6. customwas finally purified by preparative HPLC

Sources & evidence

ORD record
ord-14abbf3adccc4ac0a0adcaa2784d9294
Source dataset
uspto-grants-2015_03
Patent number
US08969565B2

Reaction notes

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