Triethylamine → 9-Chloro-3-methyl-5-{1-[2-(pyridin-3-yloxy)-acetyl]-piperidin-3-yl}-5H-isoxazolo[4,3-c]quinolin-4-one

HRID 2212196

Reaction equation

HRID 2212196 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.N1C=CC=CC=1CC[C:32](O)=[O:33].Cl.CN(C)[CH2:38][CH2:39][CH2:40][N:41]=[C:42]=NCC.[OH:47]N1C2N=CC=CC=2N=N1.C(N([CH2:62][CH3:63])CC)C>CN(C)C1C=CN=CC=1.CN(C)C=O>[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]([C:62](=[O:47])[CH2:63][O:33][C:32]4[CH:42]=[N:41][CH:40]=[CH:39][CH:38]=4)[CH2:14]3)[C:9]=2[CH:10]=[CH:11][CH:12]=1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 181649HOAtHCID 5642923-(Pyridin-2-yl)propanoic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 219637129-Chloro-3-methyl-5-piperidin-3-yl-5H-isoxazolo[4,3-c]quinolin-4-one hydroiodide

Product 1

HCID 219636999-Chloro-3-methyl-5-{1-[2-(pyridin-3-yloxy)-acetyl]-piperidin-3-yl}-5H-isoxazolo[4,3-c]quinolin-4-oneYield 77.3%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Procedure

Add 9-chloro-3-methyl-5-piperidin-3-yl-5H-isoxazolo[4,3-c]quinolin-4-one hydroiodide (50 mg, 0.11 mmol), 2-pyridine propionic acid (100 mg, 0.33 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (26 mg, 0.13 mmol), 1-hydroxy-7-azabenzotriazole (18 mg, 0.13 mmol), 4-dimethylamino-pyridine (1 mg, 0.01 mmol), and dimethylformamide (3 mL) to a dry roundbottom flask. Stir the reaction under nitrogen, and add triethylamine (30 μL, 0.22 mmol) dropwise. Stir the solution under nitrogen at room temperature overnight. Concentrate the solution and dissolve in 20% isopropanol/chloroform, washed with saturated aqueous sodium bicarbonate solution, brine, dry over magnesium sulfate and concentrate. Purify by flash chromatography on silica gel (eluting with 0–2% methanol/chloroform) to give 38.5 mg of the title compound as a white solid, 76% yield. 1H NMR: consistent with structure. MS (ion spray) 451 (M+).

Workup

  1. customthe reaction under nitrogen
  2. stirringStir the solution under nitrogen at room temperature overnight
  3. concentrationConcentrate the solution
  4. dissolutiondissolve in 20% isopropanol/chloroform
  5. washwashed with saturated aqueous sodium bicarbonate solution, brine
  6. dry with materialdry over magnesium sulfate
  7. concentrationconcentrate
  8. customPurify by flash chromatography on silica gel (eluting with 0–2% methanol/chloroform)

Sources & evidence

ORD record
ord-2acb0064197f4046a27b9fbddc1d0c5a
Source dataset
uspto-grants-2006_09
Patent number
US07101891B2

Linked notes

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