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

HRID 870624Notes

Reaction equation

HRID 870624 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.[C:16]([C:19]1[CH:24]=[CH:23][C:22](B(O)O)=[CH:21][CH:20]=1)(=O)[NH2:17].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>[NH2:17][CH2:16][C:19]1[CH:24]=[CH:23][C:22]([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:21][CH:20]=1

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 27378114-Aminocarbonylphenylboronic acidHCID 574706223-bromo-N-(2-methoxyethyl)imidazo[1,2-b]pyridazin-6-amine

Product 1

HCID 866963213-(4-(aminomethyl)phenyl)-N-(2-methoxyethyl)imidazo[1,2-b]pyridazin-6-amineYield 14.4%

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 (57.6 mg, 0.21 mmol), (4-carbamoylphenyl)boronic acid (87.4 mg, 0.53 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (7.7 mg, 0.011 mmol) and potassium phosphate (134 mg, 0.63 mmol) was added 1:1 Dimethoxyethane/water (0.75 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 (neutral) to afford 3-(4-(aminomethyl)phenyl)-N-(2-methoxyethyl)imidazo[1,2-b]pyridazin-6-amine (9 mg, 14% yield) as a white solid: 1H NMR (METHANOL-d4) δ: 8.29 (d, J=8.6 Hz, 2H), 7.98 (d, J=8.6 Hz, 2H), 7.89 (s, 1H), 7.66 (d, J=9.6 Hz, 1H), 6.79 (d, J=9.9 Hz, 1H), 3.69 (t, J=5.6 Hz, 2H), 3.59 (t, J=5.4 Hz, 2H), 3.42 (s, 3H); LRMS (ESI) m/e 312.2 [(M+H)+, calcd for C16H18N5O2 312.2].

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 (neutral)

Sources & evidence

ORD record
ord-debae2291e834c22894c728de5bd74ae
Source dataset
uspto-grants-2015_03
Patent number
US08969565B2

Reaction notes

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