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

HRID 2212195

Reaction equation

HRID 2212195 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.[N:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1[CH2:30][CH2:31][C:32](O)=[O:33].Cl.CN(C)CCCN=C=NCC.ON1C2N=CC=CC=2N=N1.C(N(CC)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:32](=[O:33])[CH2:31][CH2:30][C:25]4[CH:26]=[CH:27][CH:28]=[CH:29][N:24]=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 219637209-Chloro-3-methyl-5-[1-(3-pyridin-2-yl-propionyl)-piperidin-3-yl]-5H-isoxazolo[4,3-c]quinolin-4-oneYield 77.6%

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 (20 mg, 0.13 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; wash with saturated aqueous sodium bicarbonate solution and 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. washwash with saturated aqueous sodium bicarbonate solution and brine
  6. dry with materialdry over magnesium sulfate
  7. concentrationand concentrate
  8. customPurify by flash chromatography on silica gel (eluting with 0–2% methanol/chloroform)

Sources & evidence

ORD record
ord-1d0529684373416cb15e36ac09d2a65f
Source dataset
uspto-grants-2006_09
Patent number
US07101891B2

Linked notes

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