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Nitrogen → 3-(1,5-dimethyl-1H-indol-2-yl)-8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazine

HRID 226089
Notes
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Reaction equation

HRID 226089 reaction equation
[CH2:1]([CH:3]([C:6]1[C:7]2[N:8]([C:13](I)=[C:14]([CH3:16])[N:15]=2)[N:9]=[C:10]([CH3:12])[CH:11]=1)[CH2:4][CH3:5])[CH3:2].C([C:21]1[CH:22]=[CH:23][CH:24]=[C:25]2[C:29]=1[N:28]([CH3:30])[C:27](C)=[CH:26]2)(C)C.[C:32]([O-])([O-])=O.[Cs+].[Cs+].N#N>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].CCOC(C)=O.CN(C=O)C>[CH3:30][N:28]1[C:29]2[C:25](=[CH:24][C:23]([CH3:32])=[CH:22][CH:21]=2)[CH:26]=[C:27]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]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

8

Reactant 4

HCID 947NitrogenHCID 10796Cesium carbonateHCID 577526818-(1-Ethyl-propyl)-3-iodo-2,6-dimethyl-imidazo[1,2-b]pyridazineHCID 688581427-isopropyl-1,2-dimethyl-1H-indole

Product 1

HCID 577526543-(1,5-dimethyl-1H-indol-2-yl)-8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazineYield 4.8%

Reagents, catalysts & solvents

3
HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
130 °C

Procedure

A solution of 8-(1-ethyl-propyl)-3-iodo-2,6-dimethyl-imidazo[1,2-b]pyridazine (0.30 g, 0.87 mmol), 7-isopropyl-1,2-dimethyl-1H-indole (0.33 g, 1.76 mmol), Cs2CO3 (0.57 g, 1.75 mmol), and DMF (5 mL), is degassed with N2 for 20 minutes. Pd2(dba)3 (0.040 g, 0.044 mmol is added and the solution is heated at 130° C. overnight. The solution is diluted EtOAc (30 mL) washed with water (2×30 mL), brine (30 mL) dried over MgSO4, filtered and concentrated. The residue is purified by ISCO (20%-30% EtOAc gradient) to furnish the title compound (0.017 g, 0.042 mmol, 4.8%). 1H NMR (CDCl3), δ 1.14-1.46 (m, 6H), 1.76-1.95 (m, 4H), 2.30 (s, 3H), 2.42 (s, 3H), 2.45 (s, 3H), 3.38-3.48 (m, 1H), 3.86-3.97 (m, 1H), 4.04 (s, 3H), 6.64 (s, 1H), 6.99-7. LC/MS (m/z): calcd. for C26H34N4 (M+H)+: 403.3. found: 403.4.

Workup

  1. washwashed with water (2×30 mL), brine (30 mL)
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue is purified by ISCO (20%-30% EtOAc gradient)

Sources & evidence

ORD record
ord-4b88e88b30e848ef86f7e9f09dd5565f
Source dataset
uspto-grants-2009_07
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07557103B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes