1,2-Dimethoxyethane → 5-(6-Butylamino-imidazo[1,2-b]pyridazin-3-yl)-indan-1-one

HRID 870676Notes

Reaction equation

HRID 870676 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.CC1(C)C(C)(C)OB([C:24]2[CH:25]=[C:26]3[C:30](=[CH:31][CH:32]=2)[C:29](=[O:33])[CH2:28][CH2:27]3)O1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].COCCOC>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].O>[CH2:12]([NH:11][C:8]1[CH:9]=[CH:10][C:5]2[N:6]([C:2]([C:24]3[CH:25]=[C:26]4[C:30](=[CH:31][CH:32]=3)[C:29](=[O:33])[CH2:28][CH2:27]4)=[CH:3][N:4]=2)[N:7]=1)[CH2:13][CH2:14][CH3:15]

Participants

7

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 62657Potassium Phosphate, TribasicHCID 185417105-(tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1H-inden-1-oneHCID 866963223-Bromo-6-(butylamino)imidazo[1,2-b]pyridazine

Product 1

HCID 866963775-(6-Butylamino-imidazo[1,2-b]pyridazin-3-yl)-indan-1-oneYield 85.3%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 3-bromo-N-butylimidazo[1,2-b]pyridazin-6-amine (400 mg, 1.5 mmol), 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1H-inden-1-one (770 mg, 3.0 mmol), dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium (II) dichloromethane adduct (240 mg, 0.30 mmol), potassium phosphate (1.0 g, 4.5 mmol), DME (6 mL) and H2O (2 mL) was heated in a sealed vessel at 80° C. for 12 h. The reaction was cooled to RT, then the organic layer was separated and concentrated under reduced pressure to afford an oil that was purified by flash chromatography (SiO2) to afford 5-(6-butylamino-imidazo[1,2-b]pyridazin-3-yl)-indan-1-one (410 mg, 85%) as a pink solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 8.52 (s, 1H), 8.22 (d, J=8.1 Hz, 1H), 8.07 (s, 1H), 7.78 (s, 1H), 7.65 (d, J=8.1 Hz, 1H), 7.17 (t, J=5.4 Hz, 1H), 6.75 (d, J=9.6 Hz, 1H), 3.22-3.42 (m, 3H), 3.05-3.18 (m, 2H), 2.58-2.71 (m, 2H), 1.58-1.73 (m, 2H), 1.34-1.51 (m, 2H), 0.89-1.00 (m, 3H); LCMS (ESI) m/e 321.2 [(M+H)+, calcd for C19H21N4O 321.2].

Workup

  1. temperatureThe reaction was cooled to RT
  2. customthe organic layer was separated
  3. concentrationconcentrated under reduced pressure
  4. customto afford an oil that
  5. customwas purified by flash chromatography (SiO2)

Sources & evidence

ORD record
ord-ab9437289b1e42489a197ba131207848
Source dataset
uspto-grants-2015_03
Patent number
US08969565B2

Reaction notes

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