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

HRID 870623Notes

Reaction equation

HRID 870623 reaction equation
Br[C:2]1[N:6]2[N:7]=[C:8]([NH:11][CH2:12][CH2:13][O: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+]>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(COC)OC.O>[C:13]([OH:14])(=[O:25])[CH3:12].[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][O:14][CH3:15])[CH:9]=[CH:10][C:5]3=[N:4][CH:3]=2)=[CH:20][CH:19]=1

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 2734312(4-(Aminomethyl)phenyl)boronic acidHCID 574706223-bromo-N-(2-methoxyethyl)imidazo[1,2-b]pyridazin-6-amine

Product 1

HCID 866963203-(4-(aminomethyl)phenyl)-N-(2-methoxyethyl)imidazo[1,2-b]pyridazin-6-amine mono acetic acid salt

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 18180031Water 1,2-dimethoxyethaneSolvent

Conditions

Temperature
160 °C

Procedure

To a mixture of 3-bromo-N-(2-methoxyethyl)imidazo[1,2-b]pyridazin-6-amine (229 mg, 0.85 mmol), (4-(aminomethyl)phenyl)boronic acid (395 mg, 2.11 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (62 mg, 0.085 mmol) and potassium phosphate (540 mg, 2.54 mmol) was added 1:1 Dimethoxyethane/water (3 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-(2-methoxyethyl)imidazo[1,2-b]pyridazin-6-amine mono acetic acid salt as a white solid: 1H NMR (METHANOL-d4) δ: 8.18-8.33 (m, J=8.3 Hz, 2H), 7.82 (s, 1H), 7.67 (d, J=9.6 Hz, 1H), 7.53-7.58 (m, J=8.3 Hz, 2H), 6.78 (d, J=9.6 Hz, 1H), 4.14 (s, 2H), 3.68 (t, J=5.7 Hz, 2H), 3.58 (t, J=5.4 Hz, 2H), 3.42 (s, 3H), 1.93 (s, 3H); LRMS (ESI) m/e 298.2 [(M+H)+, calcd for C16H20N5O 298.2]

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-6d32a3fbea86499ca7f0cc925e3dc6e2
Source dataset
uspto-grants-2015_03
Patent number
US08969565B2

Reaction notes

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