Tetrahydrofuran → HCID 21949968, compound

HRID 2215816Notes

Reaction equation

HRID 2215816 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.[CH3:15][C:16]1[CH:24]=[C:23]2[C:19]([C:20]([C:25](=O)[C:26](OC)=[O:27])=[CH:21][NH:22]2)=[CH:18][CH:17]=1.CC(C)([O-])C.[K+].C1COCC1>CN(C=O)C>[CH3:15][C:16]1[CH:24]=[C:23]2[C:19]([C:20]([C:25]3[C:26](=[O:27])[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:21][NH:22]2)=[CH:18][CH:17]=1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 114353972-(1-methyl-1H-indol-7-yl)acetamideHCID 21950015HCID 21950015, compoundHCID 23665647Potassium tert-butoxide2×

Product 1

HCID 21949968HCID 21949968, compoundYield 46.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of 2-(1-methyl-1H-indol-7-yl)acetamide (260 mg, 1.38 mmol) and methyl 2-(6-Methyl-1H-indol-3-yl)oxoacetate (300 mg, 1.38 mmol) in DMF (5.4 mL) was added a 1.0 M solution of potassium tert-butoxide in THF (1.38 mL, 1.38 mmol) at 4° C. under N2. The reaction was stirred for 20 min at this temperature, and additional KOtBu (2.76 mL, 2.76 mmol) was added. The resulting dark red solution was heated to 50° C. and stirred overnight. The mixture was cooled to room temperature and quenched with 1.0 N HCl (9 mL) and poured into EtOAc (300 mL). The organic layer was separated, washed with saturated aqueous NaHCO3 (150 mL), and brine (3×150 mL). The solution was dried (MgSO4), filtered, and concentrated to a red solid. Flash chromatography (SiO2, 30% EtOAc/hexanes) gave the title compound (227 mg, 46%) as a red solid, mp 200–220° C. dec. 1H NMR (DMSO-d6) δ 11.72 (s, 1H), 11.09 (s, 1H), 7.90 (s, 1H), 7.59 (m, 1H), 7.24 (s, 1H), 7.10 (s, 1H), 6.96 (m, 1H), 6.83 (m, 1H), 6.45 (s, 1H), 6.27 (m, 1H), 6.11 (m, 1H), 3.64 (s, 3H), 2.18 (s, 3H). MS (APCI): m/z=356 [C22H17N3O2+H]+

Workup

  1. additionwas added
  2. temperatureThe mixture was cooled to room temperature
  3. customquenched with 1.0 N HCl (9 mL)
  4. additionpoured into EtOAc (300 mL)
  5. customThe organic layer was separated
  6. washwashed with saturated aqueous NaHCO3 (150 mL), and brine (3×150 mL)
  7. dry with materialThe solution was dried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated to a red solid

Sources & evidence

ORD record
ord-3657f3e430f441da89dd81705dd5fc17
Source dataset
uspto-grants-2006_09
Patent number
US07109229B2

Reaction notes

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