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

HRID 2212201

反応式

HRID 2212201 の反応式
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.[OH:24][C@H:25]([C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[CH2:26][C:27](O)=[O:28].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:27](=[O:28])[CH2:26][CH:25]([OH:24])[C:30]4[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=4)[CH2:14]3)[C:9]=2[CH:10]=[CH:11][CH:12]=1

参加物

8

反応物 5

HCID 8471TriethylamineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 2735057(S)-3-Hydroxy-3-phenylpropionic acidHCID 219637129-Chloro-3-methyl-5-piperidin-3-yl-5H-isoxazolo[4,3-c]quinolin-4-one hydroiodide

生成物 1

HCID 219636989-Chloro-5-[1-(3-hydroxy-3-phenyl-propionyl)-piperidin-3-yl]-3-methyl-5H-isoxazolo[4,3-c]quinolin-4-one収率 67.3%

試薬・触媒・溶媒 2

HCID 142844-(Dimethylamino)pyridine触媒HCID 6228Dimethylformamide溶媒

実験手順

To a dry roundbottom flask add 9-chloro-3-methyl-5-piperidin-3-yl-5H-isoxazolo[4,3-c]quinolin-4-one hydroiodide (50 mg, 0.11 mmol), (S)-3-hydroxy-3-phenylpropanoic acid (22 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). 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 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 34.5 mg of the title compound as a white solid, 66% yield. 1H NMR: consistent with structure. MS (ion spray) 466 (M+).

後処理

  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 1N HCl, 1N sodium thiosulfate, 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 0–1.5% methanol/chloroform)

出典と根拠

ORDレコード
ord-18ffb3fd97744e4197c4498c5f4403cf
出典データセット
uspto-grants-2006_09
特許番号
US07101891B2

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