Potassium Carbonate → HCID 22030676, compound

HRID 454235Notes

Reaction equation

HRID 454235 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][N:21]([CH3:24])[CH2:20][CH2:19]3)=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][N:3]=1.[F:25][C:26]1[CH:34]=[C:33]2[C:29]([CH:30]=[CH:31][NH:32]2)=[CH:28][C:27]=1[OH:35].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.O>[F:25][C:26]1[CH:34]=[C:33]2[C:29]([CH:30]=[CH:31][NH:32]2)=[CH:28][C:27]=1[O:35][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][N:21]([CH3:24])[CH2:20][CH2:19]3)=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][N:3]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 112450614-Chloro-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinazolineHCID 220309296-Fluoro-1H-indol-5-ol

Product 1

HCID 22030676HCID 22030676, compoundYield 48%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
95 °C

Procedure

A mixture of 4-chloro-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinazoline (282 mg, 0.662 mmol), 6-fluoro-5-hydroxyindole (120 mg, 0.794 mmol), (prepared as described for the starting material in Example 242), in DMF (3 ml) containing potassium carbonate (137 mg, 0.994 mmol) was heated at 95° C. for 3 hours. After cooling, the residue was poured in water (12 ml) and the pH was adjusted to 8. 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 preparative column chromatography on C18 silica eluting with 60% methanol in aqueous ammonium carbonate (2g ammonium carbonate/liter saturated with CO2). The fractions containing the expected product were combined and evaporated. The residue was triturated with ether and the solid was filtered, dried under vacuum to give 4-(6-fluoroindol-5-yloxy)-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinazoline (147 mg, 48%).

Workup

  1. custom(prepared
  2. temperatureAfter cooling
  3. extractionThe mixture was extracted with ethyl acetate
  4. customThe organic layer was separated
  5. washwashed with water, brine
  6. dry with materialdried (MgSO4)
  7. customevaporated
  8. customThe residue was purified by preparative column chromatography on C18 silica eluting with 60% methanol in aqueous ammonium carbonate (2g ammonium carbonate/liter saturated with CO2)
  9. additionThe fractions containing the expected product
  10. customevaporated
  11. customThe residue was triturated with ether
  12. filtrationthe solid was filtered
  13. customdried under vacuum

Sources & evidence

ORD record
ord-b5eb1e58b6304973aae292ffe6631ea9
Source dataset
uspto-grants-2013_07
Patent number
US08492560B2

Reaction notes

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