Succinic anhydride → (S)-N-(alpha-ethylbenzyl)-3-[2-(3-carboxypropanoyl)aminoethoxy]-2-phenylquinoline-4-carboxamide

HRID 651066Notes

Reaction equation

HRID 651066 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])[CH2:35][CH2:34]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])[CH2:34][CH2:35][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 7922Succinic anhydrideHCID 10764865(S)-N-(alpha-ethylbenzyl)-3-(2-aminoethoxy)-2-phenylquinoline-4-carboxamide

Product 1

HCID 12968614(S)-N-(alpha-ethylbenzyl)-3-[2-(3-carboxypropanoyl)aminoethoxy]-2-phenylquinoline-4-carboxamideYield 56.7%

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 0.6 g (6.2 mmol) of succinic anhydride were dissolved in 50 ml of toluene; some triturated molecular sieves were added and the reaction mixture was refluxed in a Dean Stark apparatus for 4 hours. The reaction mixture was evaporated in vacuo to dryness, dissolved in 100 ml of CH2Cl2 and washed with sat. sol. NaCl, 20% citric acid and sat. sol. NaCl. The organic layer was dried over Na2SO4 and evaporated in vacuo to dryness to yield 2.3 g of the crude product which was purified by flash column chromatography on 230-400 mesh silica gel, eluting initially with a mixture of CH2Cl2/MeOH 9:1 and then with a mixture of CH2Cl2/MeOH 8:2. The crude solid obtained was triturated with i-Pr2O/i-PrOH, washed and dried to yield 1.4 g of the title compound.

Workup

  1. additionsome triturated molecular sieves were added
  2. temperaturethe reaction mixture was refluxed in a Dean Stark apparatus for 4 hours
  3. customThe reaction mixture was evaporated in vacuo to dryness
  4. dissolutiondissolved in 100 ml of CH2Cl2
  5. washwashed with sat. sol. NaCl, 20% citric acid and sat. sol. NaCl
  6. dry with materialThe organic layer was dried over Na2SO4
  7. customevaporated in vacuo to dryness
  8. customto yield 2.3 g of the crude product which
  9. customwas purified by flash column chromatography on 230-400 mesh silica gel
  10. washeluting initially with a mixture of CH2Cl2/MeOH 9:1
  11. additionwith a mixture of CH2Cl2/MeOH 8:2
  12. customThe crude solid obtained
  13. customwas triturated with i-Pr2O/i-PrOH
  14. washwashed
  15. customdried

Sources & evidence

ORD record
ord-25a67caf0af947e19138d0a673a7edf9
Source dataset
uspto-grants-2001_08
Patent number
US06277862B1

Reaction notes

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