2-Bromo-6-(methylsulfonyl)pyridine → 8-(1-Ethyl-propyl)-3-[5-(6-methanesulfonyl-pyridin-2-yl)-3-methyl-thiophen-2-yl]-2,6-dimethyl-imidazo[1,2-b]pyridazine

HRID 1432606Notes

Reaction equation

HRID 1432606 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([S:8]([CH3:11])(=[O:10])=[O:9])[N:3]=1.C([Li])CCC.Br[C:18]1[S:22][C:21]([C:23]2[N:27]3[N:28]=[C:29]([CH3:37])[CH:30]=[C:31]([CH:32]([CH2:35][CH3:36])[CH2:33][CH3:34])[C:26]3=[N:25][C:24]=2[CH3:38])=[C:20]([CH3:39])[CH:19]=1>[Cl-].[Cl-].[Zn+2].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]>[CH2:33]([CH:32]([C:31]1[C:26]2[N:27]([C:23]([C:21]3[S:22][C:18]([C:2]4[CH:7]=[CH:6][CH:5]=[C:4]([S:8]([CH3:11])(=[O:10])=[O:9])[N:3]=4)=[CH:19][C:20]=3[CH3:39])=[C:24]([CH3:38])[N:25]=2)[N:28]=[C:29]([CH3:37])[CH:30]=1)[CH2:35][CH3:36])[CH3:34]

Participants

6

Reactant 3

HCID 134334222-Bromo-6-(methylsulfonyl)pyridineHCID 579329433-(5-Bromo-3-methyl-thiophen-2-yl)-8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazineHCID 178418339Butyllithium

Product 1

HCID 579330898-(1-Ethyl-propyl)-3-[5-(6-methanesulfonyl-pyridin-2-yl)-3-methyl-thiophen-2-yl]-2,6-dimethyl-imidazo[1,2-b]pyridazineYield 27.5%

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst

Procedure

Using a procedure similar to Example 25, 2-bromo-6-methanesulfonyl-pyridine (0.29 mL, 1.22 mmol), 1.3 M n-Bu-Li (0.82 mL, 1.07 mmol), ZnCl2 (2.14 mL, 1.07 mmol), 3-(5-bromo-3-methyl-thiophen-2-yl)-8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazine (0.40 g, 1.02 mmol) and PdCl2(dppf) (0.037 g, 0.051 mmol) furnish the title compound (0.13 g, 0.28 mmol, 27%). 1H NMR (CDCl3), 60.88 (t, J=7.5 Hz, 6H), 1.75-1.93 (m, 4H), 2.18 (s, 3H), 2.50 (s, 3H), 2.52 (s, 3H), 3.30 (s, 3H), 3.30-3.38 (m, 1H), 6.70 (s, 1H), 7.64 (s, 1H), 7.83 (dd, J=7.6, 0.8 Hz, 1H), 7.89 (dd, J=7.9, 0.8 Hz, 1H), 7.93 (dd, J=7.9, 7.6 Hz, 1H). LC/MS (m/z): calcd. for C24H28N4O2S2 (M+H)+: 469.3; found: 469.2.

Sources & evidence

ORD record
ord-41491503a0b44accada898ef6f736fc7
Source dataset
uspto-grants-2009_11
Patent number
US07612067B2

Reaction notes

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