Tetrahydrofuran → HCID 21949978, compound

HRID 2215818Notes

Reaction equation

HRID 2215818 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.[C:15]([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])#[N:16].CC(C)([O-])C.[K+].C1COCC1>CN(C=O)C>[C:15]([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)#[N:16]

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 10633084HCID 10633084, compoundHCID 114353972-(1-methyl-1H-indol-7-yl)acetamideHCID 23665647Potassium tert-butoxide

Product 1

HCID 21949978HCID 21949978, compoundYield 10.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of 2-(1-methyl-1H-indol-7-yl)acetamide (296 mg, 1.57 mmol) and methyl 2-(5-cyano-1H-indol-3-yl)oxoacetate (356 mg, 1.56 mmol) in DMF (6.5 mL) was added a 1.0 M solution of potassium tert-butoxide in THF (4.8 mL, 4.8 mmol) dropwise over 20 min at 4° C. under N2. The resulting dark red solution was heated up to 50° C. for 6 h. The mixture was cooled to 4° C. and quenched with 1.0 N hydrochloric acid (10 mL) and poured into EtOAc (100 mL). The organic layer was separated, washed with saturated NaHCO3 (60 mL), saturated NaCl (60 mL), dried (MgSO4), and concentrated to a red solid. Filtration from a slurry in CH2Cl2 (15 mL) afforded the first batch of the title compound (58 mg, 7.4%) as a red crystalline solid, mp 220° C. dec. Tritration of the concentrated filtrate with Et2O (8.0 mL) afforded a second batch of the title compound (288 mg, 36.9%). 1H NMR (DMSO-d6) δ 8.09 (s, 1H), 7.68 (m, 1H), 7.51 (m, 1H), 7.28–7.19 (m, 2H), 7.09–6.92 (m, 2H), 6.47 (m, 2H), 3.60 (s, 3H). MS (ESI): m/z=367 [C22H14N4O2+H]+

Workup

  1. temperatureThe mixture was cooled to 4° C.
  2. customquenched with 1.0 N hydrochloric acid (10 mL)
  3. additionpoured into EtOAc (100 mL)
  4. customThe organic layer was separated
  5. washwashed with saturated NaHCO3 (60 mL), saturated NaCl (60 mL)
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated to a red solid
  8. filtrationFiltration from a slurry in CH2Cl2 (15 mL)

Sources & evidence

ORD record
ord-8d4d99fb066c4f86b660b15a754fb4bc
Source dataset
uspto-grants-2006_09
Patent number
US07109229B2

Reaction notes

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