Tributylvinyltin → 3-((6-fluoro-1-methyl-1H-indazol-5-yl)methyl)-6-vinylimidazo[1,2-b]pyridazine

HRID 456175Notes

Reaction equation

Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([CH2:11][C:12]3[CH:13]=[C:14]4[C:18](=[CH:19][C:20]=3[F:21])[N:17]([CH3:22])[N:16]=[CH:15]4)=[CH:9][N:10]=2)[N:7]=1.[CH2:23]([Sn](CCCC)(CCCC)C=C)[CH2:24]CC>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:21][C:20]1[CH:19]=[C:18]2[C:14]([CH:15]=[N:16][N:17]2[CH3:22])=[CH:13][C:12]=1[CH2:11][C:8]1[N:6]2[N:7]=[C:2]([CH:23]=[CH2:24])[CH:3]=[CH:4][C:5]2=[N:10][CH:9]=1

Participants

Conditions

Temperature: 120 °C

Procedure

To a degassed solution of 6-chloro-3-((6-fluoro-1-methyl-1H-indazol-5-yl)methyl)imidazo[1,2-b]pyridazine (400 mg, 1.267 mmol), was added Pd(Ph3P)4 (220 mg, 0.190 mmol) and tributyl(vinyl)stannane (422 mg, 1.330 mmol). The reaction mixture was heated to 120° C. for overnight. Then the reaction was quenched with NH4Cl(aq), extracted with DCM, dried over Na2SO4 and concentrated in vacuo to give a residue, which was purified by silica gel column chromatography with gradient Hex:EA to give 3-((6-fluoro-1-methyl-1H-indazol-5-yl)methyl)-6-vinylimidazo[1,2-b]pyridazine (168 mg, 43%). 1H-NMR (400 MHz, DMSO-d6) δ ppm 8.09 (d, 1H), 7.97 (s, 1H), 7.63 (d, 1H), 7.55 (d, 1H), 7.54 (d, 1H), 7.50 (s, 1H), 6.84 (dd, 1H), 6.31 (d, 1H), 5.72 (d, 1H), 4.37 (s, 2H), 3.98 (s, 3H). LCMS (method B): [MH]+=308, tR=2.49 min.

Workup

customThen the reaction was quenched with NH4Cl(aq)
extractionextracted with DCM
dry with materialdried over Na2SO4
concentrationconcentrated in vacuo
customto give a residue, which
customwas purified by silica gel column chromatography with gradient Hex

Sources & evidence

ORD record: ord-2471fbbd49ac472d84645c019f88a9e9
Source dataset: uspto-grants-2013_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08497368B2

Reaction notes

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