Triethylamine → N-(4-Chlorobenzyl)-2-[(1R)-1-hydroxyethyl]-8-(4-morpholinylmethyl)-6-oxo-6H-pyrrolo[3,2,1-ij]quinoline-5-carboxamide

HRID 1060602ノート

反応式

HRID 1060602 の反応式
[Cl:1][C:2]1[CH:30]=[CH:29][C:5]([CH2:6][NH:7][C:8]([C:10]2[CH:11]=[N:12][C:13]3[C:18]([C:19]=2[OH:20])=[CH:17][C:16]([CH2:21][N:22]2[CH2:27][CH2:26][O:25][CH2:24][CH2:23]2)=[CH:15][C:14]=3I)=[O:9])=[CH:4][CH:3]=1.CCN(CC)CC.[CH3:38][C@@H:39]([OH:42])[C:40]#[CH:41]>C(Cl)(Cl)Cl.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[Cl:1][C:2]1[CH:30]=[CH:29][C:5]([CH2:6][NH:7][C:8]([C:10]2[C:19](=[O:20])[C:18]3[C:13]4=[C:14]([CH:41]=[C:40]([C@H:39]([OH:42])[CH3:38])[N:12]4[CH:11]=2)[CH:15]=[C:16]([CH2:21][N:22]2[CH2:27][CH2:26][O:25][CH2:24][CH2:23]2)[CH:17]=3)=[O:9])=[CH:4][CH:3]=1

参加物

7

反応物 3

HCID 8471TriethylamineHCID 638102(2R)-but-3-yn-2-olHCID 178522928N-(4-chlorobenzyl)-4-hydroxy-8-iodo-6-(4-morpholinylmethyl)-3-quinolinecarboxamide

生成物 1

HCID 491965N-(4-Chlorobenzyl)-2-[(1R)-1-hydroxyethyl]-8-(4-morpholinylmethyl)-6-oxo-6H-pyrrolo[3,2,1-ij]quinoline-5-carboxamide収率 13%

試薬・触媒・溶媒 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 178418476HCID 178418476、化合物触媒HCID 6212Chloroform溶媒

実験手順

To a suspension of N-(4-chlorobenzyl)-4-hydroxy-8-iodo-6-(4-morpholinylmethyl)-3-quinolinecarboxamide (300 mg), PdCl2(PPh3)2 (39.2 mg), CuI (12.8 mg), and Et3N (0.16 mL) in CHCl3 (5.6 mL) is added (R)-(+)-3-butyn-2-ol (0.053 mL). The reaction is stirred at room temperature for 2 days. The reaction is condensed to remove CHCl3. The solvent is replaced with ETOH (5.6 mL) and additional Et3N (0.16 mL) is added to the reaction mixture. N2 is passed over the surface and the reaction is heated at 60° C. overnight, then allowed to cool to room temperature. The reaction mixture is condensed, adsorbed onto silica, and chromatographed eluting with 1% MeOH in CH2Cl2 to 3% MeOH in CH2Cl2. Product-containing fractions are combined, condensed, and recrystallized from hot acetonitrile to afford 33.8 mg (13%) of N-(4-chlorobenzyl)-2-[(1R)-1-hydroxyethyl]-8-(4-morpholinylmethyl)-6-oxo-6H-pyrrolo[3,2,1-ij]quinoline-5-carboxamide as a tan solid.

後処理

  1. customcondensed
  2. customto remove CHCl3
  3. additionis added to the reaction mixture
  4. temperaturethe reaction is heated at 60° C. overnight
  5. temperatureto cool to room temperature
  6. customcondensed
  7. customchromatographed
  8. washeluting with 1% MeOH in CH2Cl2 to 3% MeOH in CH2Cl2
  9. customcondensed
  10. customrecrystallized from hot acetonitrile

出典と根拠

ORDレコード
ord-27b9c10bd891406abc28b8345ed7d0e0
出典データセット
uspto-grants-2003_02
特許番号
US06525049B2

反応ノート

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