Cesium carbonate → 7-Benzyloxy-4-(4-fluoro-2-methylindol-5-yloxy)-6-methoxycinnoline

HRID 2180123

Reaction equation

HRID 2180123 reaction equation
[CH2:1]([O:8][C:9]1[CH:18]=[C:17]2[C:12]([C:13](Cl)=[CH:14][N:15]=[N:16]2)=[CH:11][C:10]=1[O:20][CH3:21])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:22][C:23]1[C:31]([OH:32])=[CH:30][CH:29]=[C:28]2[C:24]=1[CH:25]=[C:26]([CH3:33])[NH:27]2.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C>[CH2:1]([O:8][C:9]1[CH:18]=[C:17]2[C:12]([C:13]([O:32][C:31]3[C:23]([F:22])=[C:24]4[C:28](=[CH:29][CH:30]=3)[NH:27][C:26]([CH3:33])=[CH:25]4)=[CH:14][N:15]=[N:16]2)=[CH:11][C:10]=1[O:20][CH3:21])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonate2×HCID 103520364-fluoro-2-methyl-1H-indol-5-ol2×HCID 219910087-Benzyloxy-4-chloro-6-methoxy cinnoline

Product 1

HCID 101374817-Benzyloxy-4-(4-fluoro-2-methylindol-5-yloxy)-6-methoxycinnolineYield 39%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
95 °C

Procedure

A mixture of 7-benzyloxy-4-chloro-6-methoxy cinnoline (2 g, 6.66 mmol), (prepared as described for the starting material in Example 1), 4-fluoro-5-hydroxy-2-methylindole (1.32 g, 7.99 mmol), (prepared as described for the starting material in Example 1), and cesium carbonate (3.2 g, 9.98 mmol) in DMF (40 ml) was heated at 95° C. for 1.5 hours. 4-Fluoro-5-hydroxy-2-methylindole (82 mg, 0.5 mmol) and cesium carbonate (3.2 g, 9.98 mmol) were added. The mixture was stirred for 1.5 hours at 115° C. The mixture was cooled, the solid was filtered and the filtrate was evaporated under vacuum. The residue was purified by column chromatography, eluting with methylene chloride/ethyl acetate (90/10 followed by 80/20) followed by methylene chloride/ethyl acetate/methanol (80/18/2). The fractions containing the expected product were combined and evaporated and the residue was triturated with ether/pentane (1/1). The solid was filtered, washed with pentane and dried under vacuum to give 7-benzyloxy-4-(4-fluoro-2-methylindol-5-yloxy)-6-methoxycinnoline (1.1 g, 39%).

Workup

  1. custom(prepared
  2. custom(prepared
  3. temperatureThe mixture was cooled
  4. filtrationthe solid was filtered
  5. customthe filtrate was evaporated under vacuum
  6. customThe residue was purified by column chromatography
  7. washeluting with methylene chloride/ethyl acetate (90/10 followed by 80/20)
  8. additionThe fractions containing the expected product
  9. customevaporated
  10. customthe residue was triturated with ether/pentane (1/1)
  11. filtrationThe solid was filtered
  12. washwashed with pentane
  13. customdried under vacuum

Sources & evidence

ORD record
ord-63d8f4327bec437ea8c1b2a818934aa0
Source dataset
uspto-grants-2005_05
Patent number
US06887874B2

Linked notes

Loading…