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Dichloromethane → 2-{[(aminocarbonyl)amino]methyl}-N-(4-chlorobenzyl)-8-(4-morpholinylmethyl)-6-oxo-6H-pyrrolo[3,2,1-ij]quinoline-5-carboxamide

HRID 1841532
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HRID 1841532 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.[CH2:31]([NH:34][C:35]([NH2:37])=[O:36])[C:32]#[CH:33].C(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.CCN(CC)CC.CCO>[NH2:37][C:35]([NH:34][CH2:31][C:32]1[N:12]2[C:13]3[C:18]([C:19](=[O:20])[C:10]([C:8]([NH:7][CH2:6][C:5]4[CH:29]=[CH:30][C:2]([Cl:1])=[CH:3][CH:4]=4)=[O:9])=[CH:11]2)=[CH:17][C:16]([CH2:21][N:22]2[CH2:27][CH2:26][O:25][CH2:24][CH2:23]2)=[CH:15][C:14]=3[CH:33]=1)=[O:36]
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

8

반응물 3

HCID 6344DichloromethaneHCID 2777182(Prop-2-yn-1-yl)ureaHCID 178522928N-(4-chlorobenzyl)-4-hydroxy-8-iodo-6-(4-morpholinylmethyl)-3-quinolinecarboxamide

생성물 1

HCID 4919642-{[(aminocarbonyl)amino]methyl}-N-(4-chlorobenzyl)-8-(4-morpholinylmethyl)-6-oxo-6H-pyrrolo[3,2,1-ij]quinoline-5-carboxamide수율 7%

시약·촉매·용매 4

HCID 24350
Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)
촉매
3회
HCID 178418476HCID 178418476, 화합물촉매2회
HCID 702Ethanol용매
HCID 8471Triethylamine용매2회

실험 절차

A solution of N-(4-chlorobenzyl)-4-hydroxy-8-iodo-6-(4-morpholinylmethyl)-3-quinolinecarboxamide (300 mg), PdCl2(PPh3)2 (19.7 mg), CuI (5.3 mg), Et3N (10.4 mL), and prop-2-ynylurea (60.3 mg) is stirred at room temperature overnight. Distilled CH2Cl2 (10.4 mL) and additional PdCl2(PPh3)2 (19.7 mg) and CuI (5.3 mg) are added. The reaction is stirred at room temperature overnight. The reaction mixture is condensed, adsorbed onto silica, and chromatographed eluting with 2% MeOH in CH2Cl2 to 6.5% MeOH in CH2Cl2. Product containing fractions are combined and condensed to afford a mixture of cyclized and uncyclized materials. To a scintillation vial is added the mixture, EtOH (4 mL), Et3N (0.1 mL), and CuI (˜1 mg). The suspension is heated at 70° C. overnight. The reaction mixture is condensed, adsorbed onto silica, and chromatographed eluting with 6% MeOH in CH2Cl2 then 7% MeOH in CH2Cl2. Product-containing fractions are combined and condensed to afford a solid. The solid is suspended in CH2CT2/hexanes and filtered to afford 19.7 mg (7%) of 2-{[(aminocarbonyl)amino]methyl}-N-(4-chlorobenzyl)-8-(4-morpholinylmethyl)-6-oxo-6H-pyrrolo[3,2,1-ij]quinoline-5-carboxamide as a white solid.

후처리

  1. customcondensed
  2. customchromatographed
  3. washeluting with 2% MeOH in CH2Cl2 to 6.5% MeOH in CH2Cl2
  4. additionProduct containing fractions
  5. customcondensed
  6. customto afford
  7. additiona mixture of cyclized and uncyclized materials
  8. temperatureThe suspension is heated at 70° C. overnight
  9. customcondensed
  10. customchromatographed
  11. washeluting with 6% MeOH in CH2Cl2
  12. customcondensed
  13. customto afford a solid
  14. filtrationfiltered

출처 및 근거

ORD 기록
ord-089e63238a3b4e08994a46d700961165
출처 데이터셋
uspto-grants-2004_01
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US06683181B2

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