Tetrahydrofuran → HCID 21950051, compound

HRID 2215820Notes

Reaction equation

HRID 2215820 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.[F:15][C:16]([F:33])([F:32])[C:17]1[CH:18]=[C:19]2[C:23](=[CH:24][CH:25]=1)[NH:22][CH:21]=[C:20]2[C:26](=O)[C:27](OC)=[O:28].CC(C)([O-])C.[K+].C1COCC1>CN(C=O)C>[F:32][C:16]([F:15])([F:33])[C:17]1[CH:18]=[C:19]2[C:23](=[CH:24][CH:25]=1)[NH:22][CH:21]=[C:20]2[C:26]1[C:27](=[O:28])[NH:14][C:12](=[O:13])[C:11]=1[C:9]1[CH:8]=[CH:7][CH:6]=[C:5]2[C:10]=1[N:2]([CH3:1])[CH:3]=[CH:4]2

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 114353972-(1-methyl-1H-indol-7-yl)acetamideHCID 21950033HCID 21950033, compoundHCID 23665647Potassium tert-butoxide2×

Product 1

HCID 21950051HCID 21950051, compoundYield 35%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of 2-(1-methyl-1H-indol-7-yl)acetamide (208 mg, 1.1 mmol) and methyl 2-(5-trifluoromethyl-1H-indol-3-yl)oxoacetate (300 mg, 1.1 mmol) in DMF (5.4 mL) was added a 1.0 M solution of potassium tert-butoxide in THF (1.1 mL, 1.1 mmol) at 4° C. under N2. The reaction was stirred for 20 min at this temperature, and additional KOtBu (2.2 mL, 2.2 mmol) was added. The resulting dark red solution was heated up to 50° C. over night. The mixture was cooled to room temperature and quenched with 1 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 (157 mg, 35%) as a red solid, mp 270–280° C. dec. 1H NMR (DMSO-d6) δ 12.24 (s, 1H), 11.26 (s, 1H), 8.11 (s, 1H), 7.63 (m, 1H), 7.55 (m, 1H), 7.27 (m, 2H), 6.92 (m, 2H), 6.65 (s, 1H), 6.49 (s, 1H), 3.73 (s, 3H). MS (ESI): m/z=411 [C22H14F3N3O2+H]+

Workup

  1. additionwas added
  2. temperatureThe mixture was cooled to room temperature
  3. customquenched with 1 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-50e250ea28a041d58088233796b9ead7
Source dataset
uspto-grants-2006_09
Patent number
US07109229B2

Reaction notes

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