Tetrahydrofuran → 3-(6-Ethyl-1H-indol-3-yl)-4-(1-methyl-1H-indol-7-yl)pyrrole-2,5-dione

HRID 2215826Notes

Reaction equation

HRID 2215826 reaction equation
[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][C:9]=2[CH2:11][C:12]([NH2:14])=[O:13])[CH:4]=[CH:3]1.[CH2:15]([C:17]1[CH:25]=[C:24]2[C:20]([C:21]([C:26](=O)[C:27](OC)=[O:28])=[CH:22][NH:23]2)=[CH:19][CH:18]=1)[CH3:16].CC(C)([O-])C.[K+].C1COCC1>CN(C=O)C>[CH2:15]([C:17]1[CH:25]=[C:24]2[C:20]([C:21]([C:26]3[C:27](=[O:28])[NH:14][C:12](=[O:13])[C:11]=3[C:9]3[CH:8]=[CH:7][CH:6]=[C:5]4[C:10]=3[N:2]([CH3:1])[CH:3]=[CH:4]4)=[CH:22][NH:23]2)=[CH:19][CH:18]=1)[CH3:16]

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 114353972-(1-methyl-1H-indol-7-yl)acetamideHCID 21949969Methyl 2-(6-ethyl-1H-indol-3-yl)oxoacetateHCID 23665647Potassium tert-butoxide

Product 1

HCID 219500283-(6-Ethyl-1H-indol-3-yl)-4-(1-methyl-1H-indol-7-yl)pyrrole-2,5-dioneYield 30%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of 2-(1-methyl-1H-indol-7-yl)acetamide (370 mg, 1.97 mmol) and methyl 2-(6-ethyl-1H-indol-3-yl)oxoacetate (446 mg, 1.93 mmol) in DMF (8.0 mL) at 4° C. under N2, was added a 1.0 M solution of potassium tert-butoxide in THF (6.0 mL, 6.0 mmol) dropwise over 20 min. The reaction was heated to 50° C. and stirred for 7 h at this temperature. The reaction mixture was then cooled to room temp and quenched with 1.0 N hydrochloric acid (5.0 mL), extracted with EtOAc (2×15 mL), washed with saturated NaHCO3 (30 mL), saturated NaCl (30 mL), dried (MgSO4), filtered and concentrated. Flash chromatography (SiO2, 50% EtOAc/hexanes containing 1% TEA) gave the title compound (214 mg, 30%) as a red solid, mp 98–100° C. 1H NMR (DMSO-d6) δ 11.69 (s, 1H), 11.06 (s, 1H), 7.78 (m, 1H), 7.60 (m, 1H), 7.28 (m, 1H), 7.16 (s, 1H), 6.95 (m, 1H), 6.86 (m, 1H), 6.50 (m, 1H), 6.32 (m, 1H), 6.20 (m, 1H), 3.69 (s, 3H), 3.32 (m, 2H), 1.11 (m, 3H). MS (ESI, negative mode): m/z=368 [C23H19N3O2−H]−

Workup

  1. temperatureThe reaction mixture was then cooled to room temp
  2. customquenched with 1.0 N hydrochloric acid (5.0 mL)
  3. extractionextracted with EtOAc (2×15 mL)
  4. washwashed with saturated NaHCO3 (30 mL), saturated NaCl (30 mL)
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-beffebf682394ecb9a4dbe018a3987a6
Source dataset
uspto-grants-2006_09
Patent number
US07109229B2

Reaction notes

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