Tetrahydrofuran → HCID 57932961, compound

HRID 1432700Notes

Reaction equation

HRID 1432700 reaction equation
[CH3:1][N:2]([CH3:9])[C:3]1[C:7]([CH3:8])=[CH:6][S:5][CH:4]=1.C1COCC1.[Li]CCCC.[CH2:20]([CH:22]([C:25]1[C:26]2[N:27]([C:32](I)=[C:33]([CH3:35])[N:34]=2)[N:28]=[C:29]([CH3:31])[CH:30]=1)[CH2:23][CH3:24])[CH3:21]>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]>[CH2:20]([CH:22]([C:25]1[C:26]2[N:27]([C:32]([C:6]3[S:5][CH:4]=[C:3]([N:2]([CH3:9])[CH3:1])[C:7]=3[CH3:8])=[C:33]([CH3:35])[N:34]=2)[N:28]=[C:29]([CH3:31])[CH:30]=1)[CH2:23][CH3:24])[CH3:21]

Participants

8

Reactant 4

HCID 8028TetrahydrofuranHCID 2777715HCID 2777715, compoundHCID 577526818-(1-Ethyl-propyl)-3-iodo-2,6-dimethyl-imidazo[1,2-b]pyridazineHCID 178418339Butyllithium

Product 1

HCID 57932961HCID 57932961, compoundYield 18%

Reagents, catalysts & solvents 3

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

Procedure

To a −78° C. solution of dimethyl-(4-methyl-thiophen-3-yl)-amine (0.43 g, 3.06 mmol) and THF (5 mL) is added 1.6 M n-BuLi (1.91 mL, 3.06 mmol). The solution is stirred for 1 hour, then 0.5 M ZnCl2 (6.1 mL, 3.06 mmol) is added and the solution warmed to ambient temperature. After 30 minutes 8-(1-ethyl-propyl)-3-iodo-2,6-dimethyl-imidazo[1,2-b]pyridazine (0.70 g, 2.04 mmol) and PdCl2(dppf) (0.075 g, 0.10 mmol) is added and the solution heated at 65° C. overnight. The solution is diluted with EtOAc (35 mL), washed with sat. NH4Cl (30 mL), dried over MgSO4, filtered and concentrated. The residue is purified by ISCO flash chromatography (15%-30% EtOAc gradient) furnish the title compound (0.13 g, 0.36 mmol, 18%). 1H NMR (CDCl3) δ 0.86 (t, J=7.5 Hz, 6H), 1.72-1.90 (m, 4H), 2.03 (s, 3H), 2.45 (s, 3H), 2.50 (s, 3H), 2.77 (s, 6H), 3.28-3.37 (m, 1H), 6.63 (s, 1H), 6.65 (s, 1H). LC/MS (m/z): calcd. for C20H28N4S (M+H)+: 357.2; found: 357.2

Workup

  1. temperaturethe solution heated at 65° C. overnight
  2. washwashed with sat. NH4Cl (30 mL)
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue is purified by ISCO flash chromatography (15%-30% EtOAc gradient)

Sources & evidence

ORD record
ord-3ac89f1169ef415da3949f178a3ca0bd
Source dataset
uspto-grants-2009_11
Patent number
US07612067B2

Reaction notes

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