Tetrahydrofuran → 3-(4-Fluoro-1H-indol-3-yl)-4-(1-methyl-1H-indol-7-yl)-pyrrole-2,5-dione

HRID 2215765Notes

Reaction equation

HRID 2215765 reaction equation
CC([O-])(C)C.[K+].C1COCC1.[F:12][C:13]1[CH:21]=[CH:20][CH:19]=[C:18]2[C:14]=1[C:15]([CH2:22][C:23]([NH2:25])=[O:24])=[CH:16][NH:17]2.C[O:27][C:28](=O)[C:29]([C:31]1[CH:32]=[CH:33][CH:34]=[C:35]2[C:39]=1[N:38]([CH3:40])[CH:37]=[CH:36]2)=O>CN(C=O)C>[F:12][C:13]1[CH:21]=[CH:20][CH:19]=[C:18]2[C:14]=1[C:15]([C:22]1[C:23](=[O:24])[NH:25][C:28](=[O:27])[C:29]=1[C:31]1[CH:32]=[CH:33][CH:34]=[C:35]3[C:39]=1[N:38]([CH3:40])[CH:37]=[CH:36]3)=[CH:16][NH:17]2

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 219500362-(4-fluoro-1H-indol-3-yl)acetamideHCID 23665647Potassium tert-butoxideHCID 69642215(1-Methyl-1H-indol-7-yl)-oxo-acetic acid methyl ester

Product 1

HCID 219499653-(4-Fluoro-1H-indol-3-yl)-4-(1-methyl-1H-indol-7-yl)-pyrrole-2,5-dioneYield 55%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A 1.0 M solution of KOtBu in THF (10.6 mL, 10.6 mmol) was added to a solution of 2-(4-fluoro-1H-indol-3-yl)-acetamide (595 mg, 3.10 mmol) and (1-methyl-1H-indol-7-yl)-oxo-acetic acid methyl ester (646 mg, 2.98 mmol) in DMF (40 mL). The initially light yellow solution turned red-orange over 4 h and was then stirred 4 h at 60–70° C. The heating bath was removed, 1N HCl added and the mixture poured into EtOAc. The EtOAc layer was separated and washed with water (2×), saturated aq NaHCO3 (2×) and brine (3×), dried (MgSO4), filtered and concentrated onto SiO2. Flash chromatography (1:1 EtOAc:hexanes) afforded a red glass that was dried at 70° C. overnight giving the title compound (585 mg, 55%) as a bright red solid. 1H NMR (400 MHz, DMSO-6) 11.83 (br s, 1H), 11.21 (s, 1H), 7.53 (dd, J=7, 1 Hz, 1H), 7.40 (d, J=3 Hz, 1H), 7.25 (d, J=3 Hz, 1H), 7.21 (d, J=8 Hz, 1H), 7.0–7.08 (m, 1H), 7.86–7.04 (m, 2H), 6.65 (dd, J=11, 8 Hz, 1H), 6.44 (d, J=3 Hz, 1H), 3.71 (s, 3H). IR (CHCl3, cm−1) 1726. MS (electrospray, m/z) 360 (M++1), 358 (M−−1).

Workup

  1. customThe heating bath was removed
  2. addition1N HCl added
  3. additionthe mixture poured into EtOAc
  4. customThe EtOAc layer was separated
  5. washwashed with water (2×), saturated aq NaHCO3 (2×) and brine (3×)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated onto SiO2
  9. customFlash chromatography (1:1 EtOAc:hexanes) afforded a red glass that
  10. customwas dried at 70° C. overnight

Sources & evidence

ORD record
ord-ad396fb412224d04b3c88d234f2f5659
Source dataset
uspto-grants-2006_09
Patent number
US07109229B2

Reaction notes

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