HCID 68839933, compound → HCID 57932956, compound

HRID 1432659Notes

Reaction equation

[CH2:1]([CH:3]([C:6]1[C:7]2[N:8]([C:13]([C:17]3[S:18][C:19](I)=[CH:20][C:21]=3[O:22][CH3:23])=[C:14]([CH3:16])[N:15]=2)[N:9]=[C:10]([CH3:12])[CH:11]=1)[CH2:4][CH3:5])[CH3:2].[Br-].[S:26]1[CH:30]=[CH:29][N:28]=[C:27]1[Zn+]>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:17]3[S:18][C:19]([C:27]4[S:26][CH:30]=[CH:29][N:28]=4)=[CH:20][C:21]=3[O:22][CH3:23])=[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 a flask containing 8-(1-ethyl-propyl)-3-(5-iodo-3-methoxy-thiophen-2-yl)-2,6-dimethyl-imidazo[1,2-b]pyridazine (0.45 g, 0.99 mmol) and PdCl2(dppf) (0.057 g, 0.078 mmol) is added a 0.5 M solution of 2-thiazolylzinc bromide (9.9 mL, 4.94 mmol). The solution is heated at 65° C. overnight, diluted with EtOAc (50 mL), washed with sat. NH4Cl (50 mL), dried over MgSO4, filtered and concentrated. The residue is purified by ISCO column chromatography (15%-20% EtOAc/hexane gradient) furnish the title compound (0.29 g, 0.70 mmol, 71%). 1H NMR (CDCl3) δ0.86 (t, J=7.5 Hz, 6H), 1.72-1.90 (m, 4H), 2.51 (s, 3H), 2.53 (s, 3H), 3.28-3.37 (m, 1H), 3.93 (s, 3H), 6.67 (s, 1H), 7.28 (d, J=3.3 Hz, 1H), 7.41 (s, 1H), 7.80 (d, J=3.3 Hz, 1H). LC/MS (m/z): calcd. for C21H24N4OS2 (M+H)+: 413.6; found: 414.3.

Workup

washwashed with sat. NH4Cl (50 mL)
dry with materialdried over MgSO4
filtrationfiltered
concentrationconcentrated
customThe residue is purified by ISCO column chromatography (15%-20% EtOAc/hexane gradient)

Sources & evidence

ORD record: ord-f9e27231272340a4a17ed1509a1d7d4e
Source dataset: uspto-grants-2009_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07612067B2

Reaction notes

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