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

HRID 1432646Notes

Reaction equation

HRID 1432646 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]([C:23]#[N:24])[CH:3]=1.[Br-].[CH3:26][C:27]1[N:32]=[C:31]([Zn+])[CH:30]=[CH:29][CH:28]=1.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:31]4[CH:30]=[CH:29][CH:28]=[C:27]([CH3:26])[N:32]=4)=[CH:3][C:4]=3[C:23]#[N:24])=[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 57932902HCID 57932902, compoundHCID 178426002HCID 178426002, compound

Product 1

HCID 579330662-[8-(1-Ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazin-3-yl]-5-(6-methyl-pyridin-2-yl)-thiophene-3-carbonitrileYield 39%

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 flask containing 5-bromo-2-[8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazin-3-yl]-thiophene-3-carbonitrile (0.25 g, 0.62 mmol) and PdCl2(dppf) (0.024 g, 0.033 mmol) is added a solution of 0.5 M 6-methyl-2-pyridylzinc bromide in THF (2.50 mL, 1.24 mmol). The solution is heated at 65° C. overnight, diluted with EtOAc (30 mL), washed with sat. NH4Cl (2×30 mL), dried over MgSO4, filtered and concentrated. The residue is purified by ISCO column chromatography (15%-25% EtOAc/hexane gradient), furnish the title compound (0.11 g, 0.26 mmol, 39%). 1H NMR (CDCl3) δ 0.87 (t, J=7.5 Hz, 6H), 1.76-1.92 (m, 4H), 2.57 (s, 3H), 2.58 (s, 3H), 2.65 (s, 3H), 3.26-3.35 (m, 1H), 6.75 (s, 1H), 7.09 (d, J=7.5 Hz, 1H), 7.49 (d, J=7.9 Hz, 1H), 7.63 (dd, J=7.9, 7.5 Hz, 1H), 7.74 (s, 1H). LC/MS (m/z): calcd. for C24H25N5S (M+H)+: 416.6; found: 416.2.

Workup

  1. washwashed with sat. NH4Cl (2×30 mL)
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue is purified by ISCO column chromatography (15%-25% EtOAc/hexane gradient)

Sources & evidence

ORD record
ord-f3b4ed50e960407b899f61ac28993a55
Source dataset
uspto-grants-2009_11
Patent number
US07612067B2

Reaction notes

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