Tetrahydrofuran → HCID 21949960, compound

HRID 2215814Notes

Reaction equation

HRID 2215814 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:17]=[C:18]2[C:22](=[CH:23][CH:24]=1)[NH:21][CH:20]=[C:19]2[C:25](=O)[C:26](OC)=[O:27].CC(C)([O-])C.[K+].C1COCC1>CN(C=O)C>[CH3:15][C:16]1[CH:17]=[C:18]2[C:22](=[CH:23][CH:24]=1)[NH:21][CH:20]=[C:19]2[C:25]1[C:26](=[O:27])[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 21949959HCID 21949959, compoundHCID 23665647Potassium tert-butoxide2×

Product 1

HCID 21949960HCID 21949960, compoundYield 65%

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, 1.4 mmol) and methyl 2-(5-methyl-1H-indol-3-yl)oxoacetate (300 mg, 1.4 mmol) in DMF (5.4 mL) was added a 1.0 M solution of potassium tert-butoxide in THF (1.4 mL, 1.4 mmol) at 4° C. under N2. The reaction was stirred for 20 min, and additional potassium tert-butoxide (1.0 M, 2.8 mL, 2.8 mmol) was added. The resulting dark purple solution was heated to 50° C. and stirred over night. The mixture was cooled to 4° C. and quenched with 1.0 N hydrochloric acid (9 mL), and extracted with EtOAc (300 mL). The organic layer was separated, washed with saturated aqueous NaHCO3 (150 mL), brine (150 mL), and dried (MgSO4). The mixture was filtered, and concentrated to a red solid. Flash chromatography (SiO2, 40% EtOAc/hexanes) gave the title compound (320 mg, 65%) as a red solid, mp 174–176° C. 1H NMR (DMSO-d6) δ 8.02 (s, 1H), 7.61 (m, 1H), 7.24 (s, 1H), 7.16 (m, 1H), 6.95 (m, 1H), 6.85 (m, 1H), 6.75 (m, 1H), 6.46 (s, 1H), 5.71 (s, 1H) 3.62 (s, 3H), 1.71 (s, 3H). MS (ESI): m/z=356 [C22H17N3O2+H]+

Workup

  1. stirringstirred over night
  2. temperatureThe mixture was cooled to 4° C.
  3. customquenched with 1.0 N hydrochloric acid (9 mL)
  4. extractionextracted with EtOAc (300 mL)
  5. customThe organic layer was separated
  6. washwashed with saturated aqueous NaHCO3 (150 mL), brine (150 mL)
  7. dry with materialdried (MgSO4)
  8. filtrationThe mixture was filtered
  9. concentrationconcentrated to a red solid

Sources & evidence

ORD record
ord-7db9959e407f4bf1a94183d63a266734
Source dataset
uspto-grants-2006_09
Patent number
US07109229B2

Reaction notes

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