Cesium carbonate → Methyl 4-(8-(5,6-dimethoxypyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzoate

HRID 1755335Notes

Reaction equation

Br[C:2]1[C:3]2[N:4]([CH:18]=[CH:19][N:20]=2)[N:5]=[C:6]([C:8]2[CH:17]=[CH:16][C:11]([C:12]([O:14][CH3:15])=[O:13])=[CH:10][CH:9]=2)[CH:7]=1.[CH3:21][O:22][C:23]1[CH:24]=[CH:25][C:26]([NH2:31])=[N:27][C:28]=1[O:29][CH3:30].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:21][O:22][C:23]1[CH:24]=[CH:25][C:26]([NH:31][C:2]2[C:3]3[N:4]([CH:18]=[CH:19][N:20]=3)[N:5]=[C:6]([C:8]3[CH:17]=[CH:16][C:11]([C:12]([O:14][CH3:15])=[O:13])=[CH:10][CH:9]=3)[CH:7]=2)=[N:27][C:28]=1[O:29][CH3:30]

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of methyl 4-(8-bromoimidazo[1,2-b]pyridazin-6-yl)benzoate (0.3 g, 0.904 mmol), 5,6-dimethoxypyridin-2-amine (0.167 g, 1.084 mmol), Pd2(dba)3 (52 mg, 0.09 mmol), BINAP (225 mg, 0.362 mmol) and Cs2CO3 (0.884 g, 2.712 mmol) in dioxane (20 mL) was heated to 100° C. for 16 h in a sealed tube under N2 atmosphere. The mixture was cooled and concentrated in vacuo. The residue was purified by chromatography (silica, 10 g, 200-300 mesh, ethyl acetate:petroleum ether=1:3) to afford methyl 4-(8-(5,6-dimethoxypyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzoate (0.518 g) as a yellow solid containing unidentified impurities. LC-MS: [M+H]+=406, tR=1.766 min.

Workup

temperatureThe mixture was cooled
concentrationconcentrated in vacuo
customThe residue was purified by chromatography (silica, 10 g, 200-300 mesh, ethyl acetate:petroleum ether=1:3)

Sources & evidence

ORD record: ord-ca69b1522e704a6299a0b834f98f415d
Source dataset: uspto-grants-2015_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09169259B2

Reaction notes

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