HCID 54275688, compound → HCID 54183176, compound

HRID 363336Notes

Reaction equation

HRID 363336 reaction equation
C([Li])CCC.[F:6][C:7]1[CH:25]=[CH:24][C:10]([C:11]([NH:13][C:14]2[CH:15]=[CH:16][C:17]3[S:21][CH:20]=[C:19](Br)[C:18]=3[CH:23]=2)=[O:12])=[CH:9][CH:8]=1.[CH:26]1[C:34]2[N:29]([CH:30]=[CH:31][C:32](=O)[CH:33]=2)[CH2:28][CH:27]=1>C(OCC)C>[F:6][C:7]1[CH:25]=[CH:24][C:10]([C:11]([NH:13][C:14]2[CH:15]=[CH:16][C:17]3[S:21][CH:20]=[C:19]([C:32]4[CH2:33][CH:34]5[N:29]([CH2:28][CH2:27][CH2:26]5)[CH2:30][CH:31]=4)[C:18]=3[CH:23]=2)=[O:12])=[CH:9][CH:8]=1

Participants

5

Reactant 3

HCID 54275688HCID 54275688, compoundHCID 69592000HCID 69592000, compoundHCID 178418339Butyllithium

Product 1

HCID 54183176HCID 54183176, compound

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent3×

Conditions

Temperature
-78 °C

Procedure

A solution of 1.55 mL n-butyllithium in diethyl ether is cooled to -78° C. under a nitrogen atmosphere. To this cooled solution is added a solution of N-(4-fluorobenzoyl)-3-bromo-5-aminobenzothiophene (0.90 eq.) in diethyl ether. The reaction mixture is stirred at -78° C. for 1 hour and then to it is added dropwise a solution of 7-indolizinone (1.08 eq.) in diethyl ether. The reaction is stirred an additional 2 hours at -78° C. and is then gradually warmed to -20° C. over 55 minutes. The reaction mixture is then quenched with saturated aqueous sodium bicarbonate, diluted with additional diethyl ether and the phases separated. The organic phase is washed with saturated aqueous sodium chloride, dried over sodium sulfate and concentrated under reduced pressure. The residue is taken up in aqueous potassium hydroxide (10% in water) and heated to reflux for 15 hours. The mixture is concentrated in vacuo and the residue is subjected to flash silica gel chromatography. Fractions shown to contain product are combined and then concentrated under reduced pressure to give the title compound.

Workup

  1. stirringThe reaction is stirred an additional 2 hours at -78° C.
  2. temperatureis then gradually warmed to -20° C. over 55 minutes
  3. customThe reaction mixture is then quenched with saturated aqueous sodium bicarbonate
  4. additiondiluted with additional diethyl ether
  5. customthe phases separated
  6. washThe organic phase is washed with saturated aqueous sodium chloride
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated under reduced pressure
  9. temperatureheated
  10. temperatureto reflux for 15 hours
  11. concentrationThe mixture is concentrated in vacuo
  12. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-e2261baae4934afdb81a69e82ef78099
Source dataset
uspto-grants-1999_02
Patent number
US05874427

Reaction notes

Loading…