Cesium carbonate → 6-Cyano-4-(4-fluoro-2-methylindol-5-yloxy)-7-(3-(pyrrolidin-1-yl)propoxy)quinoline

HRID 2222399Notes

Reaction equation

Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH2:15][CH2:16][CH2:17][N:18]3[CH2:22][CH2:21][CH2:20][CH2:19]3)=[C:9]([C:12]#[N:13])[CH:10]=2)[N:5]=[CH:4][CH:3]=1.[F:23][C:24]1[C:32]([OH:33])=[CH:31][CH:30]=[C:29]2[C:25]=1[CH:26]=[C:27]([CH3:34])[NH:28]2.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C>[C:12]([C:9]1[CH:10]=[C:11]2[C:6](=[CH:7][C:8]=1[O:14][CH2:15][CH2:16][CH2:17][N:18]1[CH2:22][CH2:21][CH2:20][CH2:19]1)[N:5]=[CH:4][CH:3]=[C:2]2[O:33][C:32]1[C:24]([F:23])=[C:25]2[C:29](=[CH:30][CH:31]=1)[NH:28][C:27]([CH3:34])=[CH:26]2)#[N:13]

Participants

Conditions

Temperature: 95 °C

Procedure

A suspension of 4-chloro-6-cyano-7-(3-(pyrrolidin-1-yl)propoxy)quinoline (500 mg, 1.58 mmol), 4-fluoro-5-hydroxy-2-methylindole (314 mg, 1.9 mmol) and cesium carbonate (775 mg, 2.38 mmol) in DMF (15 ml) was heated at 95° C. for 2 hours. After removal of the volatiles by evaporation under vacuum, the residue was dissolved in methylene chloride and poured onto a column of silica and eluted with a mixture of methylene chloride/methanol (90/10) followed by methylene chloride/methanol/methanol saturated with ammonia (88/10/2). The fractions containing the expected product were combined and evaporated to give 6-cyano-4-(4-fluoro-2-methylindol-5-yloxy)-7-(3-(pyrrolidin-1-yl)propoxy)quinoline (558 mg, 79%).

Workup

customAfter removal of the volatiles
customby evaporation under vacuum
dissolutionthe residue was dissolved in methylene chloride
additionpoured onto a column of silica
washeluted with a mixture of methylene chloride/methanol (90/10)
additionThe fractions containing the expected product
customevaporated

Sources & evidence

ORD record: ord-301ad00a416d4bb49f50b8e9615dde96
Source dataset: uspto-grants-2008_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07371765B2

Reaction notes

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