Maleic Anhydride → (S,Z)-N-(alpha-ethylbenzyl)-3-[2-(3-carboxypropenoyl)aminoethoxy]-2-phenylquinoline-4-carboxamide

HRID 651065Notes

Reaction equation

HRID 651065 reaction equation
[CH2:1]([C@H:3]([NH:10][C:11]([C:13]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[N:16]=[C:15]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[C:14]=1[O:29][CH2:30][CH2:31][NH2:32])=[O:12])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)[CH3:2].[C:33]1(=[O:39])[O:38][C:36](=[O:37])[CH:35]=[CH:34]1>C1(C)C=CC=CC=1>[CH2:1]([C@H:3]([NH:10][C:11]([C:13]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[N:16]=[C:15]([C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)[C:14]=1[O:29][CH2:30][CH2:31][NH:32][C:33](=[O:39])/[CH:34]=[CH:35]\[C:36]([OH:38])=[O:37])=[O:12])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)[CH3:2]

Participants

4

Reactant 2

HCID 7923Maleic AnhydrideHCID 10764865(S)-N-(alpha-ethylbenzyl)-3-(2-aminoethoxy)-2-phenylquinoline-4-carboxamide

Product 1

HCID 70163626(S,Z)-N-(alpha-ethylbenzyl)-3-[2-(3-carboxypropenoyl)aminoethoxy]-2-phenylquinoline-4-carboxamideYield 81.3%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

2.0 g (4.7 mmol) of (S)-N-(α-ethylbenzyl)-3-(2-aminoethoxy)-2-phenylquinoline-4-carboxamide (compound of Description 4) and 0.61 g (6.2 mmol) of maleic anhydride were dissolved in 50 ml of toluene. Some molecular sieves were added and the reaction mixture was refluxed for 5 hours. After cooling, the reaction mixture was evaporated in vacuo to dryness, dissolved in CH2Cl2 and washed with sat. sol. NaCl, 20% citric acid, sat. sol. NaCl. The organic layer was dried over Na2SO4 and evaporated in vacuo to dryness. The crude product was purified by flash column chromatography on 230-400 mesh silica gel, eluting with a mixture of i-Pr2O/EtOAc 70:30 containing 0.5% of 85% formic acid, and then triturated with i-Pr2O to yield 2.0 g of the title compound.

Workup

  1. additionSome molecular sieves were added
  2. temperaturethe reaction mixture was refluxed for 5 hours
  3. temperatureAfter cooling
  4. customthe reaction mixture was evaporated in vacuo to dryness
  5. dissolutiondissolved in CH2Cl2
  6. washwashed with sat. sol. NaCl, 20% citric acid, sat. sol. NaCl
  7. dry with materialThe organic layer was dried over Na2SO4
  8. customevaporated in vacuo to dryness
  9. customThe crude product was purified by flash column chromatography on 230-400 mesh silica gel
  10. washeluting with a mixture of i-Pr2O/EtOAc 70:30 containing 0.5% of 85% formic acid
  11. customtriturated with i-Pr2O

Sources & evidence

ORD record
ord-0083d582813449b69f648c2b275ce448
Source dataset
uspto-grants-2001_08
Patent number
US06277862B1

Reaction notes

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