Potassium Phosphate, Tribasic → 4-(6-(Butylamino)imidazo[1,2-b]pyridazin-3-yl)benzaldehyde

HRID 870634Notes

Reaction equation

HRID 870634 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.[CH:16]([C:18]1[CH:23]=[CH:22][C:21](B(O)O)=[CH:20][CH:19]=1)=[O: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>[CH2:12]([NH:11][C:8]1[CH:9]=[CH:10][C:5]2[N:6]([C:2]([C:21]3[CH:22]=[CH:23][C:18]([CH:16]=[O:17])=[CH:19][CH:20]=3)=[CH:3][N:4]=2)[N:7]=1)[CH2:13][CH2:14][CH3:15]

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 5910734-Formylphenylboronic AcidHCID 866963223-Bromo-6-(butylamino)imidazo[1,2-b]pyridazine

Product 1

HCID 866963304-(6-(Butylamino)imidazo[1,2-b]pyridazin-3-yl)benzaldehydeYield 72%

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-butylimidazo[1,2-b]pyridazin-6-amine (100 mg, 0.37 mmol), (4-formylphenyl)boronic acid (139 mg, 0.93 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (13.5 mg, 0.02 mmol) and potassium phosphate (236 mg, 1.11 mmol) was added 3:1 dimethoxyethane/water (2 mL). The resulting mixture was heated at 160° C. (microwave) for 6 min. After the reaction was cooled down and separated into two layers, the dark upper layer 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 4-(6-(butylamino)imidazo[1,2-b]pyridazin-3-yl)benzaldehyde (78 mg, 72% yield) as a yellow solid: 1H NMR (METHANOL-d4) δ: 10.01 (s, 1H), 8.47 (d, J=8.6 Hz, 2H), 7.98-8.03 (m, 2H), 7.97 (s, 1H), 7.66 (d, J=9.6 Hz, 1H), 6.77 (d, J=9.6 Hz, 1H), 3.42 (t, J=7.1 Hz, 2H), 1.74 (t, J=7.2 Hz, 2H), 1.52 (d, J=7.8 Hz, 2H), 1.03 (t, J=7.5 Hz, 4H); LRMS (ESI) m/e 295.2 [(M+H)+, calcd for C17H19N4O 295.2].

Workup

  1. temperatureAfter the reaction was cooled down
  2. customseparated into two layers
  3. filtrationthe dark upper layer was then filtered
  4. additiondiluted with a mixture of 1:1:1 methanol/water/acetonitrile
  5. filtrationfiltered again
  6. filtrationThe filtration
  7. customwas finally purified by preparative HPLC (neutral)

Sources & evidence

ORD record
ord-2d1d2dea86db4eda83fd88ff5c5b2052
Source dataset
uspto-grants-2015_03
Patent number
US08969565B2

Reaction notes

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