Tetrahydrofuran → HCID 21950046, compound

HRID 2215830Notes

Reaction equation

HRID 2215830 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]([O:17][C:18]1[CH:26]=[C:25]2[C:21]([C:22]([C:27](=O)[C:28](OC)=[O:29])=[CH:23][NH:24]2)=[CH:20][CH:19]=1)[CH3:16].CC(C)([O-])C.[K+].C1COCC1>CN(C=O)C>[CH2:15]([O:17][C:18]1[CH:26]=[C:25]2[C:21]([C:22]([C:27]3[C:28](=[O:29])[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:23][NH:24]2)=[CH:20][CH:19]=1)[CH3:16]

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 114353972-(1-methyl-1H-indol-7-yl)acetamideHCID 21949971HCID 21949971, compoundHCID 23665647Potassium tert-butoxide2×

Product 1

HCID 21950046HCID 21950046, compoundYield 26%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of 2-(1-methyl-1H-indol-7-yl)acetamide (381 mg, 2.02 mmol) and methyl 2-(6-ethoxy-1H-indol-3-yl)oxoacetate (500 mg, 2.02 mmol) in DMF (17 mL) was added a 1.0 M solution of potassium tert-butoxide in THF (2.0 mL, 2.0 mmol) at 4° C. under N2. The reaction was stirred for 20 min at this temperature, and additional potassium tert-butoxide (1.0 M, 4.1 mL, 4.1 mmol) was added. The resulting dark purple solution was heated up to 70° C. over night. The mixture was cooled to 4° C. and quenched with 1.0 N hydrochloric acid (12 mL) and poured into EtOAc (500 mL). The organic layer was separated, dried (MgSO4), and concentrated to a red solid. Flash chromatography (SiO2, 30% EtOAc/hexanes) gave the title compound (200 mg, 26%) as a red solid, mp 212–215° C. 1H NMR (CDCl3) δ 8.44 (s, 1H), 7.88 (s, 1H), 7.68 (m, 1H), 7.60 (s, 1H), 7.00 (m, 2H), 6.92 (s, 1H), 6.72 (s, 1H), 6.52 (s, 1H), 6.32 (s, 2H), 3.92 (q, J=6.5 Hz, 2H), 3.72 (s, 3H), 1.38 (t, J=6.5 Hz, 3H). MS (ESI, Negative Mode): m/z=384 [C23H19N3O3−H]−

Workup

  1. additionwas added
  2. temperatureThe mixture was cooled to 4° C.
  3. customquenched with 1.0 N hydrochloric acid (12 mL)
  4. additionpoured into EtOAc (500 mL)
  5. customThe organic layer was separated
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated to a red solid

Sources & evidence

ORD record
ord-e94d820cc62041dba8306d35efd35c64
Source dataset
uspto-grants-2006_09
Patent number
US07109229B2

Reaction notes

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