Tetrahydrofuran → 8-(1-ethyl-propyl)-2,6-dimethyl-3-[3-methyl-5-(1-methyl-1H-pyrazol-3-yl)-thiophen-2-yl]-imidazo[1,2-b]pyridazine

HRID 1432592Notes

Reaction equation

HRID 1432592 reaction equation
Br[C:2]1[S:6][C:5]([C:7]2[N:11]3[N:12]=[C:13]([CH3:21])[CH:14]=[C:15]([CH:16]([CH2:19][CH3:20])[CH2:17][CH3:18])[C:10]3=[N:9][C:8]=2[CH3:22])=[C:4]([CH3:23])[CH:3]=1.C([Li])CCC.C1COCC1.Br[C:35]1[CH:39]=[CH:38][N:37]([CH3:40])[N:36]=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]>[CH2:17]([CH:16]([C:15]1[C:10]2[N:11]([C:7]([C:5]3[S:6][C:2]([C:35]4[CH:39]=[CH:38][N:37]([CH3:40])[N:36]=4)=[CH:3][C:4]=3[CH3:23])=[C:8]([CH3:22])[N:9]=2)[N:12]=[C:13]([CH3:21])[CH:14]=1)[CH2:19][CH3:20])[CH3:18]

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 149486373-Bromo-1-methyl-1H-pyrazoleHCID 579329433-(5-Bromo-3-methyl-thiophen-2-yl)-8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazineHCID 178418339Butyllithium

Product 1

HCID 579330408-(1-ethyl-propyl)-2,6-dimethyl-3-[3-methyl-5-(1-methyl-1H-pyrazol-3-yl)-thiophen-2-yl]-imidazo[1,2-b]pyridazineYield 10%

Reagents, catalysts & solvents 2

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

Procedure

Using a procedure analogous to Example 31, 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), 1.42 M n-Bu-Li (0.75 mL, 1.07 mmol), 0.5 M ZnCl2 in THF (2.14 mL, 1.07 mmol), 3-bromo-1-methyl-1H-pyrazole (Pavlik, J.; Kurzweil, E.; J. Org. Chem., 1991, 56, 22, 6313) (0.20 g, 1.22 mmol) and PdCl2(dppf) (0.037 g, 0.051 mmol) furnish the title compound (0.041 g, 0.10 mmol, 10%). 1H NMR (CDCl3) δ 0.90 (t, J=7.5 Hz, 6H), 1.75-1.94 (m, 4H), 2.15 (s, 3H), 2.51 (s, 3H), 2.52 (s, 3H), 3.31-3.41 (m, 1H), 3.95 (s, 3H), 6.47 (d, J=2.2 Hz, 1H), 6.67 (s, 1H), 7.25 (s, 1H), 7.36 (d, J=2.2 Hz, 1H). LC/MS (m/z): calcd. for C22H27N5S (M+H)+: 394.3; found: 394.2.

Sources & evidence

ORD record
ord-98bd2af0dc294317a7a843aceb891330
Source dataset
uspto-grants-2009_11
Patent number
US07612067B2

Reaction notes

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