Trifluoroacetic acid → N-(6-chloro-3-(pyridin-4-yl)imidazo[1,2-b]pyridazin-2-yl)acetamide

HRID 1162492Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8](I)=[C:9]([NH:11][C:12](=[O:14])[CH3:13])[N:10]=2)[N:7]=1.[N:16]1[CH:21]=[CH:20][C:19](B(O)O)=[CH:18][CH:17]=1.C(=O)([O-])[O-].[Na+].[Na+].FC(F)(F)C(O)=O>[Pd+2].ClC1C=C[C-](P(C2C=CC=CC=2)C2C=CC=CC=2)C=1Cl.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].O.O1CCOCC1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([C:19]3[CH:20]=[CH:21][N:16]=[CH:17][CH:18]=3)=[C:9]([NH:11][C:12](=[O:14])[CH3:13])[N:10]=2)[N:7]=1

Participants

Conditions

Temperature: 80 °C

Procedure

A sealable vial was charged with N-(6-chloro-3-iodoimidazo[1,2-b]pyridazin-2-yl)acetamide (74.0 mg, 220 μmol), 4-pyridylboronic acid (32.4 mg, 264 μmol), sodium carbonate (93.2 mg, 880 μmol), and dichloro 1,1′-bis(diphenylphosphino)ferrocene palladium(II) (122 mg, 220 μmol). The vial was sealed with a septum cap and 1,4-dioxane (2 mL) was added under positive N2 flow followed by water (1 mL). The mixture was sparged with N2 for 10 min and heated at 80° C. for 18 h. The solution was concentrated and the residue was taken up in minimal MeOH/DMSO and purified by preparative HPLC (Gilson GX-281, Middletown, Wis.: 5-90% (0.1% TFA in CH3CN) in H2O over 15 min, Phenomenex, Zorbax 00F-4435-UO 150×30 mm, 5 micron) to afford N-(6-chloro-3-(pyridin-4-yl)imidazo[1,2-b]pyridazin-2-yl)acetamide (47.0 mg, 74.3% yield) as a trifluoroacetic acid salt. LCMS (ESI positive ionization) m/z: 288.3 (M+1).

Workup

customThe vial was sealed with a septum
customcap
customThe mixture was sparged with N2 for 10 min
concentrationThe solution was concentrated
custompurified by preparative HPLC (Gilson GX-281, Middletown, Wis.: 5-90% (0.1% TFA in CH3CN) in H2O over 15 min, Phenomenex, Zorbax 00F-4435-UO 150×30 mm, 5 micron)

Sources & evidence

ORD record: ord-f14f8ea497c4423eb46520464f532fc7
Source dataset: uspto-grants-2010_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07820665B2

Reaction notes

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