Potassium Phosphate, Tribasic → 4-(6-(butylamino)imidazo[1,2-b]pyridazin-3-yl)-N-methylbenzamide

HRID 870628Notes

Reaction equation

HRID 870628 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.[CH3:16][NH:17][C:18]([C:20]1[CH:25]=[CH:24][C:23](B(O)O)=[CH:22][CH:21]=1)=[O:19].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:23]3[CH:24]=[CH:25][C:20]([C:18]([NH:17][CH3:16])=[O:19])=[CH:21][CH:22]=3)=[CH:3][N:4]=2)[N:7]=1)[CH2:13][CH2:14][CH3:15]

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 27735264-(Methylcarbamoyl)benzeneboronic acidHCID 866963223-Bromo-6-(butylamino)imidazo[1,2-b]pyridazine

Product 1

HCID 866963264-(6-(butylamino)imidazo[1,2-b]pyridazin-3-yl)-N-methylbenzamideYield 27%

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-(methylcarbamoyl)phenyl)boronic acid (166 mg, 0.93 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (15 mg, 0.02 mmol) and potassium phosphate (236 mg, 1.11 mmol) was added 1:1 Dimethoxyethane/water (5 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 4-(6-(butylamino)imidazo[1,2-b]pyridazin-3-yl)-N-methylbenzamide (32.1 mg, 27% yield) as a white solid: 1H NMR (METHANOL-d4) δ: 8.21-8.41 (m, 2H), 7.86-7.94 (m, 3H), 7.64 (d, J=9.6 Hz, 1H), 6.74 (d, J=9.6 Hz, 1H), 3.35-3.44 (m, 5H), 2.97 (s, 3H), 1.68-1.77 (m, 2H), 1.46-1.56 (m, 2H), 1.03 (t, J=7.3 Hz, 3H); LRMS (ESI) m/e 324.4 [(M+H)+, calcd for C18H22N5O 324.2].

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-9ecce2ad71b24d478924de6c1d141647
Source dataset
uspto-grants-2015_03
Patent number
US08969565B2

Reaction notes

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