Water → 6Cyano-7-(3-(1,1-dioxothiomorpholino)propoxy)-4-(2-methylindol-5-yloxy)quinoline

HRID 2222397Notes

Reaction equation

HRID 2222397 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[CH2:23][CH2:22][S:21](=[O:25])(=[O:24])[CH2:20][CH2:19]3)=[C:9]([C:12]#[N:13])[CH:10]=2)[N:5]=[CH:4][CH:3]=1.[OH:26][C:27]1[CH:28]=[C:29]2[C:33](=[CH:34][CH:35]=1)[NH:32][C:31]([CH3:36])=[CH:30]2.C(=O)([O-])[O-].[Cs+].[Cs+].O>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[CH2:23][CH2:22][S:21](=[O:25])(=[O:24])[CH2:20][CH2:19]1)[N:5]=[CH:4][CH:3]=[C:2]2[O:26][C:27]1[CH:28]=[C:29]2[C:33](=[CH:34][CH:35]=1)[NH:32][C:31]([CH3:36])=[CH:30]2)#[N:13]

Participants

6

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 833362-methyl-1H-indol-5-olHCID 597122364-Chloro-6-cyano-7-(3-(1,1-dioxothiomorpholino)propoxy)quinoline

Product 1

HCID 101849096Cyano-7-(3-(1,1-dioxothiomorpholino)propoxy)-4-(2-methylindol-5-yloxy)quinolineYield 23.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A suspension of 4-chloro-6-cyano-7-(3-(1,1-dioxothiomorpholino)propoxy)quinoline (100 mg, 0.26 mmol), (prepared as described for the starting material in Example 1), 5-hydroxy-2-methylindole (46 mg, 0.32 mmol) and cesium carbonate (129 mg, 0.39 mmol) in DMF (1 ml) was stirred for 10 minutes at ambient temperature followed by 1.5 hours at 70° C. After cooling, water (5 ml) was added. The mixture was extracted with ethyl acetate. The organic layer was separated, washed with water, brine, dried (MgSO4) and evaporated. The residue was purified by column chromatography eluting with methanol/methylene chloride/ethyl acetate (5/45/50) to give 6cyano-7-(3-(1,1-dioxothiomorpholino)propoxy)-4-(2-methylindol-5-yloxy)quinoline (30 mg, 23%).

Workup

  1. custom(prepared
  2. waitfollowed by 1.5 hours at 70° C
  3. temperatureAfter cooling
  4. extractionThe mixture was extracted with ethyl acetate
  5. customThe organic layer was separated
  6. washwashed with water, brine
  7. dry with materialdried (MgSO4)
  8. customevaporated
  9. customThe residue was purified by column chromatography
  10. washeluting with methanol/methylene chloride/ethyl acetate (5/45/50)

Sources & evidence

ORD record
ord-3220f6ab8851412b84ac75600e2f3087
Source dataset
uspto-grants-2008_05
Patent number
US07371765B2

Reaction notes

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