Nitrogen → 3-[3-Chloro-5-(6-methyl-pyridin-2-yl)-thiophen-2-yl]-8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazine

HRID 1432625Notes

Reaction equation

HRID 1432625 reaction equation
[CH2:1]([CH:3]([C:6]1[C:7]2[N:8]([CH:13]=[C:14]([CH3:16])[N:15]=2)[N:9]=[C:10]([CH3:12])[CH:11]=1)[CH2:4][CH3:5])[CH3:2].Br[C:18]1[S:22][C:21]([C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([CH3:29])[N:24]=2)=[CH:20][C:19]=1[Cl:30].C([O-])([O-])=O.[Cs+].[Cs+].N#N.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>CCOC(C)=O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CN(C=O)C>[Cl:30][C:19]1[CH:20]=[C:21]([C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([CH3:29])[N:24]=2)[S:22][C:18]=1[C:13]1[N:8]2[N:9]=[C:10]([CH3:12])[CH:11]=[C:6]([CH:3]([CH2:4][CH3:5])[CH2:1][CH3:2])[C:7]2=[N:15][C:14]=1[CH3:16]

Participants

9

Reactant 5

HCID 947NitrogenHCID 10796Cesium carbonateHCID 11776TriphenylphosphineHCID 688412672,6-Dimethyl-8-(pentan-3-yl)imidazo[1,2-b]pyridazineHCID 688441482-(5-Bromo-4-chloro-thiophen-2-yl)-6-methyl-pyridine

Product 1

HCID 579329983-[3-Chloro-5-(6-methyl-pyridin-2-yl)-thiophen-2-yl]-8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazineYield 10.1%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

A solution of 8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazine (0.39 g, 1.78 mmol), 2-(5-bromo-4-chloro-thiophen-2-yl)-6-methyl-pyridine (0.59 g, 2.04 mmol), Cs2CO3 (1.23 g, 3.77 mmol), and DMF (5 mL), is de-gassed with N2 for 15 minutes. PPh3 (0.089 g, 0.34 mmol) and Pd2(dba)3 (0.079 g, 0.86 mmol) is added and the solution heated at 110° C. for 48 hours. The solution is diluted with EtOAc (30 mL), washed with sat. NH4Cl (25 mL), dried over MgSO4, filtered and concentrated. The residue is purified by ISCO column chromatography (20%-30% EtOAc/hexane gradient) and is chromatographed (19×300 C18 Symmetry column, 20-45% water: 0.1% TFA/ACN: 0.1% TFA gradient) furnish the title compound (0.078 g, 0.18 mmol, 10%). Spectrum identical to Method A.

Workup

  1. washwashed with sat. NH4Cl (25 mL)
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue is purified by ISCO column chromatography (20%-30% EtOAc/hexane gradient)
  6. customis chromatographed (19×300 C18 Symmetry column, 20-45% water: 0.1% TFA/ACN: 0.1% TFA gradient)

Sources & evidence

ORD record
ord-a3466622400542bc9be8c9e9f022c812
Source dataset
uspto-grants-2009_11
Patent number
US07612067B2

Reaction notes

Loading…