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

HRID 1432580Notes

Reaction equation

HRID 1432580 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.[Br-].[N:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[Zn+].C1COCC1>CCOC(C)=O.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:26]4[CH:27]=[CH:28][CH:29]=[CH:30][N:25]=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

6

Reactant 3

HCID 8028TetrahydrofuranHCID 579329433-(5-Bromo-3-methyl-thiophen-2-yl)-8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazineHCID 178418723HCID 178418723, compound

Product 1

HCID 579329578-(1-Ethyl-propyl)-2,6-dimethyl-3-(3-methyl-5-pyridin-2-yl-thiophen-2-yl)-imidazo[1,2-b]pyridazineYield 89%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
65 °C

Procedure

To a mixture of 3-(5-bromo-3-methyl-thiophen-2-yl)-8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazine (0.50 g, 1.27 mmol) and PdCl2(dppf) (0.047 g, 0.064 mmol) is added a 0.5 M solution of 2-pyridylzinc bromide in THF (5.1 mL, 2.55 mmol). The mixture is stirred at 65° C. overnight, diluted with EtOAc (50 mL), washed with 10% citric acid (50 mL), water (40 mL), brine (40 mL), dried over MgSO4, filtered and concentrated. The residue is purified by ISCO column chromatography (20%-40% EtOAc/hexane gradient) furnish the title compound (0.45 g, 1.15 mmol, 89%). 1H NMR (CDCl3), δ 0.88 (t, J=7.5 Hz, 6H), 1.75-1.93 (m, 4H), 2.17 (s, 3H), 2.52 (s, 6H), 3.30-3.39 (m, 1H), 6.67 (s, 1H), 7.12-7.16 (m, 1H), 7.53 (s, 1H), 7.63-7.71 (m, 2H), 8.57 (dt, J=1.3, 4.8 Hz, 1H). LC/MS (m/z): calcd. for C23H26N4S (M+H)+: 391.6; found: 391.2.

Workup

  1. washwashed with 10% citric acid (50 mL), water (40 mL), brine (40 mL)
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue is purified by ISCO column chromatography (20%-40% EtOAc/hexane gradient)

Sources & evidence

ORD record
ord-259402c4e3e742959d3e0f607057fe99
Source dataset
uspto-grants-2009_11
Patent number
US07612067B2

Reaction notes

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