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

HRID 1060604노트

반응식

HRID 1060604 반응식
[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.[CH2:38]([O:41][CH3:42])[C:39]#[CH:40]>ClCCl.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:40]=[C:39]([CH2:38][O:41][CH3:42])[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

참가 물질

7

반응물 3

HCID 8471TriethylamineHCID 693933-MethoxypropyneHCID 178522928N-(4-chlorobenzyl)-4-hydroxy-8-iodo-6-(4-morpholinylmethyl)-3-quinolinecarboxamide

생성물 1

HCID 491966N-(4-Chlorobenzyl)-2-(methoxymethyl)-8-(4-morpholinylmethyl)-6-oxo-6H-pyrrolo[3,2,1-ij]quinoline-5-carboxamide

시약·촉매·용매 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 178418476HCID 178418476, 화합물촉매HCID 6344Dichloromethane용매2회

실험 절차

To a flame-dried flask under a nitrogen atmosphere is added N-(4-chlorobenzyl)-4-hydroxy-8-iodo-6-(4-morpholinylmethyl)-3-quinolinecarboxamide (269 mg) of Preparation 26, PdCl2(PPh3)2 (18 mg), and CuI (10 mg). The flask is back-filled with nitrogen gas and charged with dichloromethane (10 mL), Et3N (0.14 mL), and methyl propargyl ether (0.046 mL). The reaction is stirred at room temperature for 4 days. The reaction mixture is diluted with dichloromethane and partitioned against dilute aqueous sodium carbonate. The aqueous phase is extracted with two portions of dichloromethane. The combined organic layers are washed with brine, dried over sodium sulfate and concentrated under reduced pressure. The residue is flash column chromatographed on silica gel eluting with 1% to 4% methanol in dichloromethane. The product containing fractions are combined and concentrated under reduced pressure to give a yellow solid which is crystallized from toluene to afford 0.13 g of the title compound as tan needles.

후처리

  1. additionTo a flame-dried flask under a nitrogen atmosphere is added
  2. additionThe flask is back-filled with nitrogen gas
  3. custompartitioned against dilute aqueous sodium carbonate
  4. extractionThe aqueous phase is extracted with two portions of dichloromethane
  5. washThe combined organic layers are washed with brine
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customchromatographed on silica gel eluting with 1% to 4% methanol in dichloromethane
  9. additionThe product containing fractions
  10. concentrationconcentrated under reduced pressure
  11. customto give a yellow solid which
  12. customis crystallized from toluene

출처 및 근거

ORD 기록
ord-fe408207f57343658fde40d655383b92
출처 데이터셋
uspto-grants-2003_02
특허 번호
US06525049B2

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