Potassium Phosphate, Tribasic → 3-(4-(aminomethyl)phenyl)-N-butylimidazo[1,2-b]pyridazin-6-amine mono acetic acid salt

HRID 870626Notes

Reaction equation

HRID 870626 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.[NH2:16][CH2:17][C:18]1[CH:23]=[CH:22][C:21](B(O)[OH:25])=[CH:20][CH:19]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[CH2:35]([CH2:38][O:39]C)OC.O>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:38]([OH:39])(=[O:25])[CH3:35].[NH2:16][CH2:17][C:18]1[CH:23]=[CH:22][C:21]([C:2]2[N:6]3[N:7]=[C:8]([NH:11][CH2:12][CH2:13][CH2:14][CH3:15])[CH:9]=[CH:10][C:5]3=[N:4][CH:3]=2)=[CH:20][CH:19]=1

Participants

6

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 2734312(4-(Aminomethyl)phenyl)boronic acidHCID 18180031Water 1,2-dimethoxyethaneHCID 866963223-Bromo-6-(butylamino)imidazo[1,2-b]pyridazine

Product 1

HCID 866963233-(4-(aminomethyl)phenyl)-N-butylimidazo[1,2-b]pyridazin-6-amine mono acetic acid saltYield 10%

Reagents, catalysts & solvents 1

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst

Conditions

Temperature
160 °C

Procedure

To a mixture of 3-bromo-N-butylimidazo[1,2-b]pyridazin-6-amine (190 mg, 0.71 mmol), (4-(aminomethyl)phenyl)boronic acid (331 mg, 1.76 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (26 mg, 0.036 mmol) and tripotassium phosphate (452 mg, 2.13 mmol) was added 1:1 dimethoxyethane/water (10 mL). The resulting mixture was heated at 160° C. (microwave) for 6 min. The reaction was then filtered and diluted with a mixture of 1:1:1 methanol/water/acetonitrile, and then filtered again. The filtration was finally purified by preparative HPLC (acidic) to afford 3-(4-(aminomethyl)phenyl)-N-butylimidazo[1,2-b]pyridazin-6-amine mono acetic acid salt (21 mg, 10% yield) as a white solid: 1H NMR (METHANOL-d4) δ: 8.25-8.29 (m, 2H), 7.80 (s, 1H), 7.63 (d, J=9.6 Hz, 1H), 7.54 (d, J=8.3 Hz, 2H), 6.74 (s, 1H), 6.72 (s, 1H), 4.11 (s, 2H), 3.39 (t, J=7.1 Hz, 2H), 1.93 (s, 3H), 1.68-1.76 (m, 2H), 1.46-1.55 (m, 2H), 1.02 (t, J=7.5 Hz, 3H); LRMS (ESI) m/e 296.4 [(M+H)+, calcd for C17H22N5 296.2].

Workup

  1. filtrationThe reaction was then filtered
  2. additiondiluted with a mixture of 1:1:1 methanol/water/acetonitrile
  3. filtrationfiltered again
  4. filtrationThe filtration
  5. customwas finally purified by preparative HPLC (acidic)

Sources & evidence

ORD record
ord-b80c9847afe84616b09c10322b4977d9
Source dataset
uspto-grants-2015_03
Patent number
US08969565B2

Reaction notes

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