Cesium carbonate → 3-[5-(2-Piperidin-1-yl-ethoxy)-1H-indol-2-yl]-1H-quinolin-2-one

HRID 381754Notes

Reaction equation

HRID 381754 reaction equation
Cl[C:2]1[C:11]([C:12]2[N:13](C(OC(C)(C)C)=O)[C:14]3[C:19]([CH:20]=2)=[CH:18][C:17]([OH:21])=[CH:16][CH:15]=3)=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1.Cl.Cl[CH2:31][CH2:32][N:33]1[CH2:38][CH2:37][CH2:36][CH2:35][CH2:34]1.C(=O)([O-])[O-:40].[Cs+].[Cs+]>CN(C)C=O.O.C(O)(=O)C>[N:33]1([CH2:32][CH2:31][O:21][C:17]2[CH:18]=[C:19]3[C:14](=[CH:15][CH:16]=2)[NH:13][C:12]([C:11]2[C:2](=[O:40])[NH:3][C:4]4[C:9]([CH:10]=2)=[CH:8][CH:7]=[CH:6][CH:5]=4)=[CH:20]3)[CH2:38][CH2:37][CH2:36][CH2:35][CH2:34]1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 74826Piperidine, 1-(2-chloroethyl)-, hydrochlorideHCID 22285138HCID 22285138, compound

Product 1

HCID 53293753-[5-(2-Piperidin-1-yl-ethoxy)-1H-indol-2-yl]-1H-quinolin-2-one

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of tert-butyl 2-(2-chloro-3-quinolinyl)-5-hydroxy-1H-indole-1-carboxylate 1-8 (395 mg, 1.00 mmol, 1 equiv), 1-(2-chloroethyl)-piperidine hydrochloride (276 mg, 1.50 mmol, 1.50 equiv), and cesium carbonate (978 mg, 3.00 mmol, 3.00 equiv) in N,N-dimethylformamide (5 mL) was heated at 50° C. for 2 h. The reaction mixture was concentrated, and the residue was partitioned between water and ethyl acetate. The organic layer was washed with water then brine, dried over magnesium sulfate, and concentrated to give a pale-yellow foam. The foam was dissolved in a 1:1 mixture of water and acetic acid (60 mL), and the resulting solution was heated at 110° C. for 12 h. The reaction mixture was concentrated, and the residue was stirred in aqueous saturated sodium bicarbonate solution which yielded a tan solid. The tan solid was filtered, then suspended in warm ethanol (2×20 mL) and filtered to give 3-[5-(2-piperidin-1-yl-ethoxy)-1H-indol-2-yl]-1H-quinolin-2-one (1-9) as a yellow solid. The ethanolic filtrate was concentrated and the residue purified by flash column chromatography (5% ethanol saturated with ammonia in ethyl acetate to afford additional 1-9. 1H NMR (400 MHz, (CD3)2SO) δ12.14 (s, 1H), 11.41 (s, 1H), 8.50 (s, 1H), 7.73 (br d, 1H, J=7.9 Hz), 7.51 (br t, 1H, J=7.6 Hz), 7.41 (d, 1H, J=8.6 Hz), 7.37 (br d, 1H, J=8.2 Hz), 7.24 (br t, 1H, J=7.7 Hz), 7.21 (br s, 1H), 7.06 (br s, 1H), 6.76 (dd, 1H, J=8.6,2.2 Hz), 4.06 (t, 2H, J=5.9 Hz), 2.67 (t, 3H, J=5.5 Hz), 2.45 (br m, 4H), 1.51 (br m, 4H), 1.39 (br m, 2H).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. customthe residue was partitioned between water and ethyl acetate
  3. washThe organic layer was washed with water
  4. dry with materialbrine, dried over magnesium sulfate
  5. concentrationconcentrated
  6. customto give a pale-yellow foam
  7. temperaturethe resulting solution was heated at 110° C. for 12 h
  8. concentrationThe reaction mixture was concentrated
  9. customyielded a tan solid
  10. filtrationThe tan solid was filtered
  11. filtrationfiltered

Sources & evidence

ORD record
ord-80534ebe6fa24c18a8caf2e669049f12
Source dataset
uspto-grants-2001_10
Patent number
US06306874B1

Reaction notes

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