Phenylmethanesulfonyl chloride → 9-Chloro-3-methyl-5-(1-phenylmethanesulfonyl-piperidin-3-yl)-5H-isoxazolo[4,3-c]quinolin-4-one

HRID 2212199

Reaction equation

HRID 2212199 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.[C:35]1([CH2:41][S:42](Cl)(=[O:44])=[O:43])[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1>C(O)C>[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]([S:42]([CH2:41][C:35]4[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=4)(=[O:44])=[O:43])[CH2:14]3)[C:9]=2[CH:10]=[CH:11][CH:12]=1

Participants

5

Reactant 3

HCID 74740Phenylmethanesulfonyl chlorideHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 219637129-Chloro-3-methyl-5-piperidin-3-yl-5H-isoxazolo[4,3-c]quinolin-4-one hydroiodide

Product 1

HCID 219637239-Chloro-3-methyl-5-(1-phenylmethanesulfonyl-piperidin-3-yl)-5H-isoxazolo[4,3-c]quinolin-4-oneYield 73%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a 0° C. suspension of 9-chloro-3-methyl-5-piperidin-3-yl-5H-isoxazolo[4,3-c]quinolin-4-one hydroiodide (50 mg, 0.11 mmol) in ethanol (5 mL) add 1,8-diazabicyclo[5.4.0]undec-7-ene (42 μL, 0.28 mmol). Stir the solution for 10 mins. To the solution add α-toluene-sulfonyl chloride (21 mg, 0.11 mmol) and stir the reaction at 0° C. under nitrogen for 30 minutes. Quench the reaction with 1N HCl, concentrate, and extract with 20% isopropanol/chloroform (×2). Wash the combined organic layers with saturated aqueous sodium bicarbonate solution, brine, dry over magnesium sulfate and concentrate. Purify by flash chromatography on silica gel (eluting with 0–0.4% methanol/chloroform) to give 37.9 mg of the title compound as a white solid, 72% yield. 1H NMR: consistent with structure. MS (ion spray) 472 (M+).

Workup

  1. stirringstir
  2. customthe reaction at 0° C. under nitrogen for 30 minutes
  3. customQuench
  4. customthe reaction with 1N HCl
  5. concentrationconcentrate
  6. extractionextract with 20% isopropanol/chloroform (×2)
  7. washWash the combined organic layers with saturated aqueous sodium bicarbonate solution, brine
  8. dry with materialdry over magnesium sulfate
  9. concentrationconcentrate
  10. customPurify by flash chromatography on silica gel (eluting with 0–0.4% methanol/chloroform)

Sources & evidence

ORD record
ord-606f274b3ba447d89bb53890261a59cd
Source dataset
uspto-grants-2006_09
Patent number
US07101891B2

Linked notes

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