Nitrogen → 2,6-Dimethyl-3-[3-methyl-5-(6-methyl-pyridin-2-yl)-thiophen-2-yl]-imidazo[1,2-b]pyridazine

HRID 1432613Notes

Reaction equation

HRID 1432613 reaction equation
[CH3:1][C:2]1[N:3]=[C:4]2[CH:9]=[CH:8][C:7]([CH3:10])=[N:6][N:5]2[CH:11]=1.Br[C:13]1[S:17][C:16]([C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([CH3:24])[N:19]=2)=[CH:15][C:14]=1[CH3:25].C([O-])([O-])=O.[Cs+].[Cs+].N#N.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>C(Cl)Cl.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>[CH3:1][C:2]1[N:3]=[C:4]2[CH:9]=[CH:8][C:7]([CH3:10])=[N:6][N:5]2[C:11]=1[C:13]1[S:17][C:16]([C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([CH3:24])[N:19]=2)=[CH:15][C:14]=1[CH3:25]

Participants

9

Reactant 5

HCID 947NitrogenHCID 10796Cesium carbonateHCID 11776TriphenylphosphineHCID 218176672,6-Dimethylimidazo[1,2-b]pyridazineHCID 667211492-(5-Bromo-4-methyl-thiophen-2-yl)-6-methyl-pyridine

Product 1

HCID 688416742,6-Dimethyl-3-[3-methyl-5-(6-methyl-pyridin-2-yl)-thiophen-2-yl]-imidazo[1,2-b]pyridazineYield 39.8%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
130 °C

Procedure

A solution of 2,6-dimethyl-imidazo[1,2-b]pyridazine (below) (0.50 g, 3.39 mmol), 2-(5-bromo-4-methyl-thiophen-2-yl)-6-methyl-pyridine (1.00 g, 3.73 mmol), Cs2CO3 (2.32 g, 7.13 mmol) and DMF (5 mL) is de-gassed for 15 minutes with N2. Pd2(dba)3 (0.15 g, 0.16 mmol) and PPh3 (0.17 g, 0.65 mmol) is added and the solution is heated at 130° C. overnight. The solution is diluted with CH2Cl2 (30 mL) washed with water (2×25 mL), brine (25 mL) dried over MgSO4, filtered and concentrated. The residue is purified by ISCO column chromatography (100% EtOAc), followed by recrystallization from acetonitrile/water furnish the title compound (0.45 g, 1.35 mmol, 39%). 1H NMR (CDCl3), δ 2.13 (s, 3H), 2.50 (s, 3H), 2.53 (s, 3H), 2.57 (s, 3H), 6.90 (d, J=9.2 Hz, 1H), 7.01 (d, J=7.5 Hz, 1H), 7.46 (d, J=8.0 Hz, 1H), 7.52 (s, 1H), 7.56 (dd, J=8.0, 7.5 Hz, 1H), 7.77 (d, J=9.2 Hz, 1H). LC/MS (m/z): calcd. for C19H18N4S (M+H)+: 335.1; found: 335.1.

Workup

  1. washwashed with water (2×25 mL), brine (25 mL)
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue is purified by ISCO column chromatography (100% EtOAc)
  6. customfollowed by recrystallization from acetonitrile/water

Sources & evidence

ORD record
ord-e81b2d43ce944dfa8da90bf4d780e8d2
Source dataset
uspto-grants-2009_11
Patent number
US07612067B2

Reaction notes

Loading…