Hexane → HCID 57933065, compound

HRID 1432619Notes

Reaction equation

HRID 1432619 reaction equation
[O:1]1[CH:5]=[CH:4][N:3]=[CH:2]1.C([Li])(C)(C)C.CCCCCC.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>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].C1COCC1>[CH2:33]([CH:32]([C:31]1[C:26]2[N:27]([C:23]([C:21]3[S:22][C:18]([C:2]4[O:1][CH:5]=[CH:4][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

9

Reactant 4

HCID 8058HexaneHCID 9255OxazoleHCID 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 57933065HCID 57933065, compoundYield 5.2%

Reagents, catalysts & solvents 4

HCID 3007855ZincchlorideCatalystHCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-78 °C

Procedure

To a −78° C. solution of oxazole (0.14 g, 2.04 mmol) and THF (3 mL) is added 1.6 M t-Bu-Li in hexane (1.32 mL, 2.14 mmol). The mixture is stirred at −78° C. for 15 minutes. 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 (20 mL), water (20 mL), brine (20 mL), dried over MgSO4, filtered and concentrated. The residue is purified by ISCO column chromatography (20% EtOAc/hexane gradient) and is chromatographed (50×250 C18 Symmetry column, 20-70% water: 0.1% TFA/ACN: 0.1% TFA gradient) to furnish the title compound (0.020 g, 0.053 mmol, 5%). 1H NMR (CDCl3), δ 0.89 (t, J=7.5 Hz, 6H), 1.75-1.93 (m, 4H), 2.17 (s, 3H), 2.49 (s, 3H), 2.51 (s, 3H), 3.29-3.38 (m, 1H), 6.69 (s, 1H), 7.19 (s, 1H), 7.59 (s, 1H), 7.65 (s, 1H). LC/MS (m/z): calcd. for C21H24N4OS (M+H)+: 381.3; found: 381.1.

Workup

  1. temperaturethe solution warmed to ambient temperature
  2. stirringmixture is stirred at 65° C. overnight
  3. washwashed with 10% citric acid (20 mL), water (20 mL), brine (20 mL)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue is purified by ISCO column chromatography (20% EtOAc/hexane gradient)
  8. customis chromatographed (50×250 C18 Symmetry column, 20-70% water: 0.1% TFA/ACN: 0.1% TFA gradient)

Sources & evidence

ORD record
ord-c3e2fad65a4549f7944e5e00f652cc4a
Source dataset
uspto-grants-2009_11
Patent number
US07612067B2

Reaction notes

Loading…