Tetrahydrofuran → HCID 57933023, compound

HRID 1432620Notes

Reaction equation

HRID 1432620 reaction equation
[CH3:1][C:2]1[O:3][CH:4]=[CH:5][CH:6]=1.C([Li])(C)(C)C.CCCCCC.C1COCC1.Br[C:24]1[S:28][C:27]([C:29]2[N:33]3[N:34]=[C:35]([CH3:43])[CH:36]=[C:37]([CH:38]([CH2:41][CH3:42])[CH2:39][CH3:40])[C:32]3=[N:31][C:30]=2[CH3:44])=[C:26]([CH3:45])[CH:25]=1>CCOC(C)=O.[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].CCOCC>[CH2:39]([CH:38]([C:37]1[C:32]2[N:33]([C:29]([C:27]3[S:28][C:24]([C:4]4[O:3][C:2]([CH3:1])=[CH:6][CH:5]=4)=[CH:25][C:26]=3[CH3:45])=[C:30]([CH3:44])[N:31]=2)[N:34]=[C:35]([CH3:43])[CH:36]=1)[CH2:41][CH3:42])[CH3:40]

Participants

10

Reactant 5

HCID 8028TetrahydrofuranHCID 8058HexaneHCID 107972-MethylfuranHCID 579329433-(5-Bromo-3-methyl-thiophen-2-yl)-8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazineHCID 178418306HCID 178418306, compound

Product 1

HCID 57933023HCID 57933023, compoundYield 50%

Reagents, catalysts & solvents 4

HCID 3007855ZincchlorideCatalystHCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 3283Diethyl EtherSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a 0° C. mixture of 2-methylfuran (0.18 mL, 2.04 mmol) and Et2O (2 mL) is added 1.6 M t-Bu-Li in hexane (1.30 mL, 2.14 mmol). The mixture is heated at a reflux for 30 minutes, cooled to 0° C., and 0.5 M ZnCl2 in THF (4.3 mL, 2.14 mmol) is added and the solution warmed to ambient temperature. 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) is added and mixture is stirred at 65° C. overnight, diluted with EtOAc (30 mL), washed with 10% citric acid (15 mL), water (15 mL), brine (15 mL), dried over MgSO4, filtered and concentrated. The residue is purified by ISCO column chromatography (20% EtOAc/hexane gradient) furnish the title compound (0.20 g, 0.51 mmol, 50%). 1H NMR (CDCl3), δ 0.89 (t, J=7.5 Hz, 6H), 1.74-1.92 (m, 4H), 2.12 (s, 3H), 2.35 (s, 3H), 2.48 (s, 3H), 2.51 (s, 3H), 3.29-3.38 (m, 1H), 6.62 (dd, J=3.1, 0.9 Hz, 1H), 6.40 (d, J=3.1 Hz, 1H), 6.66 (s, 1H), 7.12 (s, 1H). LC/MS (m/z): calcd. for C23H27N3OS (M+H)+: 394.3; found: 394.2.

Workup

  1. temperatureThe mixture is heated at
  2. temperaturea reflux for 30 minutes
  3. temperaturethe solution warmed to ambient temperature
  4. washwashed with 10% citric acid (15 mL), water (15 mL), brine (15 mL)
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue is purified by ISCO column chromatography (20% EtOAc/hexane gradient)

Sources & evidence

ORD record
ord-5dfa55720b404eb69ebfd508277ecc65
Source dataset
uspto-grants-2009_11
Patent number
US07612067B2

Reaction notes

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