Hydrochloric Acid → 3-[1-(2-Hydroxyethyl)-6-methoxy-1H-indol-3-yl]-4-(1-methyl-1H-indol-7-yl)-pyrrole-2,5-dione

HRID 2215801Notes

Reaction equation

HRID 2215801 reaction equation
[Si]([O:8][CH2:9][CH2:10][N:11]1[C:19]2[C:14](=[CH:15][CH:16]=[C:17]([O:20][CH3:21])[CH:18]=2)[C:13]([C:22](=O)[C:23]([O:25]C)=O)=[CH:12]1)(C(C)(C)C)(C)C.[CH3:28][N:29]1[C:37]2[C:32](=[CH:33][CH:34]=[CH:35][C:36]=2[CH2:38][C:39]([NH2:41])=[O:40])[CH:31]=[CH:30]1.CC(C)([O-])C.[K+].Cl>CN(C=O)C>[OH:8][CH2:9][CH2:10][N:11]1[C:19]2[C:14](=[CH:15][CH:16]=[C:17]([O:20][CH3:21])[CH:18]=2)[C:13]([C:22]2[C:23](=[O:25])[NH:41][C:39](=[O:40])[C:38]=2[C:36]2[CH:35]=[CH:34][CH:33]=[C:32]3[C:37]=2[N:29]([CH3:28])[CH:30]=[CH:31]3)=[CH:12]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 114353972-(1-methyl-1H-indol-7-yl)acetamideHCID 23665647Potassium tert-butoxideHCID 86760260methyl {1-[2-(tert-butyldimethylsilyloxy)ethyl]-6-methoxy-1H-indol-3-yl}oxoacetate

Product 1

HCID 219499793-[1-(2-Hydroxyethyl)-6-methoxy-1H-indol-3-yl]-4-(1-methyl-1H-indol-7-yl)-pyrrole-2,5-dioneYield 86.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of methyl {1-[2-(tert-butyldimethylsilyloxy)ethyl]-6-methoxy-1H-indol-3-yl}oxoacetate (10.4 g, 26.5 mmol) and 2-(1-methyl-1H-indol-7-yl)acetamide (5.0 g, 26.5 mmol) in DMF (250 mL) was added a 1.0 M solution of potassium tert-butoxide (79.5 mL, 79.5 mmol) at room temperature and under nitrogen. The reaction was stirred overnight. A solution of concentrated HCl (10 mL) was added and the mixture was stirred at room temperature for 1 h, then quenched with water (200 mL) and diluted with EtOAc (300 mL). The two layers were separated and the aqueous phase was extracted with EtOAc (3×200 mL). The organic phases were combined and washed with water (3×300 mL), brine (500 mL), dried (MgSO4), filtered and concentrated. Flash chromatography (SiO2, 30% hexanes/EtOAc) gave the title compound (9.5 g, 86%) as a red solid. 1H NMR (300 MHz, DMSO-d6) 11.10 (s, 1H), 8.08 (s, 1H), 7.65 (d, J=6.1 Hz, 1H), 7.22 (d, J=2.8 Hz, 1H), 7.00–6.83 (m, 3H), 6.49 (d, J=2.8 Hz, 1H), 6.03 (d, J=5.8 Hz, 1H), 5.94 (d, J=6.3 Hz, 1H), 4.88 (t, J=5.3 Hz, 1H), 4.22 (t, J=5.5 Hz, 2H), 3.70–3.55 (m, 8H).

Workup

  1. stirringthe mixture was stirred at room temperature for 1 h
  2. customquenched with water (200 mL)
  3. additiondiluted with EtOAc (300 mL)
  4. customThe two layers were separated
  5. extractionthe aqueous phase was extracted with EtOAc (3×200 mL)
  6. washwashed with water (3×300 mL), brine (500 mL)
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-5971f0dafe9f4ee686d1127db2dc1893
Source dataset
uspto-grants-2006_09
Patent number
US07109229B2

Reaction notes

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