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

HRID 456899Notes

Reaction equation

HRID 456899 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 hours. 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 hours. 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) δ 12.14 (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 hours
  8. concentrationThe reaction mixture was concentrated
  9. customyielded a tan solid
  10. filtrationThe tan solid was filtered
  11. filtrationfiltered

Sources & evidence

ORD record
ord-b91f1bcb31e2422a808a70633f81b6eb
Source dataset
uspto-grants-2007_03
Patent number
US07186723B2

Reaction notes

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