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

HRID 1841532Notes

Reaction equation

HRID 1841532 reaction equation
[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]

Participants

8

Reactant 3

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

Product 1

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

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)Catalyst3×HCID 178418476HCID 178418476, compoundCatalyst2×HCID 702EthanolSolventHCID 8471TriethylamineSolvent2×

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-089e63238a3b4e08994a46d700961165
Source dataset
uspto-grants-2004_01
Patent number
US06683181B2

Reaction notes

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