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

HRID 1432572Notes

Reaction equation

[CH2:1]([CH:3]([C:6]1[C:7]2[N:8]([C:13](I)=[C:14]([CH3:16])[N:15]=2)[N:9]=[C:10]([CH3:12])[CH:11]=1)[CH2:4][CH3:5])[CH3:2].[Br-].[CH3:19][C:20]1[CH:24]=[CH:23][S:22][C:21]=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]>[CH2:1]([CH:3]([C:6]1[C:7]2[N:8]([C:13]([C:21]3[S:22][CH:23]=[CH:24][C:20]=3[CH3:19])=[C:14]([CH3:16])[N:15]=2)[N:9]=[C:10]([CH3:12])[CH:11]=1)[CH2:4][CH3:5])[CH3:2]

Participants

Conditions

Temperature: 65 °C

Procedure

To mixture of 8-(1-ethyl-propyl)-3-iodo-2,6-dimethyl-imidazo[1,2-b]pyridazine (12.0 g, 34.96 mmol) and PdCl2(dppf) (1.28 g, 1.75 mmol) is added a 0.5 M solution of 3-methyl-2-thienylzinc bromide in THF (100 mL, 50.0 mmol). The mixture is stirred at 65° C. overnight, diluted with EtOAc (500 mL), washed with 10% citric acid (500 mL), water (400 mL), brine (400 mL), dried over MgSO4, filtered and concentrated. The residue is purified by ISCO (10%-20% EtOAc/hexane gradient) furnish the title compound (8.83 g, 28.17 mmol, 81%). 1H NMR (CDCl3), δ 0.92 (t, J=7.4 Hz, 6H), 1.78-1.95 (m, 4H), 2.18 (s, 3H), 2.50 (s, 3H), 2.54 (s, 3H), 3.33-3.43 (m, 1H), 6.69 (s, 1H), 7.06 (d, J=4.9 Hz, 1H), 7.46 (d, J=4.9 Hz, 1H). LC/MS (m/z): calcd. for C18H23N3S (M+H)+: 314.6; found: 314.2.

Workup

washwashed with 10% citric acid (500 mL), water (400 mL), brine (400 mL)
dry with materialdried over MgSO4
filtrationfiltered
concentrationconcentrated
customThe residue is purified by ISCO (10%-20% EtOAc/hexane gradient)

Sources & evidence

ORD record: ord-7f75a7f644fc4b8d9e98160f2fa8c029
Source dataset: uspto-grants-2009_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07612067B2

Reaction notes

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