Potassium Carbonate → 3-[6-(4-Chlorophenyl)-5-fluoro-1-methyl-1H-indol-3-yl]-4-(7-methoxybenzofuran-3-yl)pyrrole-2,5-dione

HRID 222473Notes

Reaction equation

HRID 222473 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1I)[N:7]([CH3:12])[CH:6]=[C:5]2[C:13]1[C:14](=[O:30])[NH:15][C:16](=[O:29])[C:17]=1[C:18]1[C:22]2[CH:23]=[CH:24][CH:25]=[C:26]([O:27][CH3:28])[C:21]=2[O:20][CH:19]=1.[Cl:31][C:32]1[CH:37]=[CH:36][C:35](B(O)O)=[CH:34][CH:33]=1.C([O-])([O-])=O.[K+].[K+]>C(COC)OC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:31][C:32]1[CH:37]=[CH:36][C:35]([C:10]2[CH:9]=[C:8]3[C:4]([C:5]([C:13]4[C:14](=[O:30])[NH:15][C:16](=[O:29])[C:17]=4[C:18]4[C:22]5[CH:23]=[CH:24][CH:25]=[C:26]([O:27][CH3:28])[C:21]=5[O:20][CH:19]=4)=[CH:6][N:7]3[CH3:12])=[CH:3][C:2]=2[F:1])=[CH:34][CH:33]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 742994-Chlorophenylboronic acidHCID 248257793-(5-Fluoro-6-Iodo-1-Methyl-1h-Indol-3-Yl)-4-(7-Methoxy-1-Benzofuran-3-Yl)-1h-Pyrrole-2,5-Dione

Product 1

HCID 445827433-[6-(4-Chlorophenyl)-5-fluoro-1-methyl-1H-indol-3-yl]-4-(7-methoxybenzofuran-3-yl)pyrrole-2,5-dioneYield 51.2%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

3-(5-Fluoro-6-iodo-1-methyl-1H-indol-3-yl )-4-(7-methoxy benzofuran-3-yl)-pyrrole-2,5-dione (0.020 g, 0.039 mmol), Pd(PPh3)4 (4.5 mg, 0.004 mmol), and 4-chloro-phenylboronic acid (15.1 mg, 0.097 mmol) were dissolved in dimethoxy ethane (DME) (4 mL), and the mixture was degassed for 1 min and stirred for 10 min at room temperature. A solution of K2CO3 (2 M, 0.049 mL, 0.098 mmol) was added. The mixture was degassed again for 1 min, and stirred at 85° C. overnight. The resulting mixture was cooled to ambient temperature and poured into a mixture of 0.1 N HCl/EtOAc (15 mL/15 mL). After partition, the organic layer was washed with water, filtered, and concentrated. The residue was purified by preparative TLC using (ethyl acetate-hexane, 1:1) to afford the product as an orange solid (10 mg, 51%). The sample was purified by HPLC to give 3 mg of pure final compound.

Workup

  1. customthe mixture was degassed for 1 min
  2. customThe mixture was degassed again for 1 min
  3. stirringstirred at 85° C. overnight
  4. temperatureThe resulting mixture was cooled to ambient temperature
  5. additionpoured into a mixture of 0.1 N HCl/EtOAc (15 mL/15 mL)
  6. customAfter partition
  7. washthe organic layer was washed with water
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by preparative TLC

Sources & evidence

ORD record
ord-443a74bf891b4e03bce95b72b963df7c
Source dataset
uspto-grants-2012_06
Patent number
US08207216B2

Reaction notes

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