1,8-Diazabicyclo(5.4.0)undec-7-ene → 9-Chloro-5-[1-(2-hydroxy-3-phenyl-propyl)-piperidin-3-yl]-3-methyl-5H-isoxazolo[4,3-c]quinolin-4-one

HRID 2212200Notes

Reaction equation

HRID 2212200 reaction equation
I.[Cl:2][C:3]1[C:4]2[C:5]3[C:6](=[C:20]([CH3:23])[O:21][N:22]=3)[C:7](=[O:19])[N:8]([CH:13]3[CH2:18][CH2:17][CH2:16][NH:15][CH2:14]3)[C:9]=2[CH:10]=[CH:11][CH:12]=1.N12CCCN=C1CCCCC2.[O:35]1[CH2:44][CH:36]1[CH2:37][C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1>C(O)C.C(O)(C)C.C(Cl)(Cl)Cl>[Cl:2][C:3]1[C:4]2[C:5]3[C:6](=[C:20]([CH3:23])[O:21][N:22]=3)[C:7](=[O:19])[N:8]([CH:13]3[CH2:18][CH2:17][CH2:16][N:15]([CH2:44][CH:36]([OH:35])[CH2:37][C:38]4[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=4)[CH2:14]3)[C:9]=2[CH:10]=[CH:11][CH:12]=1

Participants

6

Reactant 3

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 948262-(Phenylmethyl)oxiraneHCID 219637129-Chloro-3-methyl-5-piperidin-3-yl-5H-isoxazolo[4,3-c]quinolin-4-one hydroiodide

Product 1

HCID 219637269-Chloro-5-[1-(2-hydroxy-3-phenyl-propyl)-piperidin-3-yl]-3-methyl-5H-isoxazolo[4,3-c]quinolin-4-oneYield 84%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 21906603Chloroform isopropyl alcoholSolvent

Conditions

Temperature
60 °C

Procedure

To a suspension of 9-chloro-3-methyl-5-piperidin-3-yl-5H-isoxazolo[4,3-c]quinolin-4-one hydroiodide (100 mg, 0.22 mmol) in ethanol (5 mL) add 1,8-diazabicyclo[5.4.0]undec-7-ene (40 μL, 0.27 mmol). Stir the solution under nitrogen. To the solution add (2,3-epoxypropyl)-benzene and heat to approximately 60° C. and stir under nitrogen overnight. Concentrate the reaction and dissolve in 20% isopropanol/chloroform, wash with 1N HCl, 1N sodium thiosulfate, saturated aqueous sodium bicarbonate solution, brine, dry over magnesium sulfate and concentrate. Purify by flash chromatography on silica gel (eluting with 0–1.5% methanol/chloroform) to give 85.0 mg of the title compound as a white solid, 84% yield. 1H NMR: consistent with structure. MS (ion spray) 452 (M+).

Workup

  1. stirringstir under nitrogen overnight
  2. concentrationConcentrate
  3. customthe reaction
  4. washwash with 1N HCl, 1N sodium thiosulfate, saturated aqueous sodium bicarbonate solution, brine
  5. dry with materialdry over magnesium sulfate
  6. concentrationconcentrate
  7. customPurify by flash chromatography on silica gel (eluting with 0–1.5% methanol/chloroform)

Sources & evidence

ORD record
ord-6152a8152b694533935296e7b7ee1b0b
Source dataset
uspto-grants-2006_09
Patent number
US07101891B2

Reaction notes

Loading…