(S)-N-(alpha-ethylbenzyl)-3-(2-aminoethoxy)-2-phenylquinoline-4-carboxamide → (S)-N-(alpha-ethylbenzyl)-3-(2-aminoacetylaminoethoxy)-2-phenylquinoline-4-carboxamide

HRID 651070Notes

Reaction equation

HRID 651070 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].C1C2C(COC([NH:50][CH2:51][C:52](Cl)=[O:53])=O)C3C(=CC=CC=3)C=2C=CC=1>C(Cl)Cl>[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:52](=[O:53])[CH2:51][NH2:50])=[O:12])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)[CH3:2]

Participants

4

Reactant 2

HCID 10764865(S)-N-(alpha-ethylbenzyl)-3-(2-aminoethoxy)-2-phenylquinoline-4-carboxamideHCID 11758879Fmoc-Gly-Cl

Product 1

HCID 54268066(S)-N-(alpha-ethylbenzyl)-3-(2-aminoacetylaminoethoxy)-2-phenylquinoline-4-carboxamideYield 17.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

3.0 g (7.1 mmol) of (S)-N-(α-ethylbenzyl)-3-(2-aminoethoxy)-2-phenylquinoline-4-carboxamide (compound of Description 4) were dissolved, under nitrogen atmosphere, in 60 ml of CH2Cl2 and 1.2 ml (8.5 mmol) of TEA were added; the solution was cooled to 0° C. and 2.7 g (8.5 mmol) of (9-fluorenylmethoxy carbonyl)glycinyl chloride (FMOC-glycinyl chloride), dissolved in 60 ml of CH2Cl2, were added dropwise. The reaction mixture was stirred at room temperature for 3 hours and then washed with sat. sol. NaCl, 20% citric acid, sat. sol. NaHCO3, sat. sol. NaCl, dried over Na2SO4 and evaporated in vacuo to dryness. The crude product was purified by gradient flash column chromatography on 230-400 mesh silica gel, utilising a mixture of hexane/EtOAc 1:1 as starting eluent and a mixture of EtOAc/MeOH 9:1 as final eluent. The product (5.0 g) was dissolved in 100 ml of a 10% solution of diethylamine in DMF and stirred at room temperature for 30 minutes. The reaction mixture was then evaporated in vacuo and purified by gradient flash column chromatography on 230-400 mesh silica gel, utilising a mixture of EtOAc/MeOH 9:1 as starting eluent and a mixture of EtOAc/MeOH 7:3 as final eluent, to yield 0.6 g of the title compound.

Workup

  1. additionwere added dropwise
  2. washwashed with sat. sol. NaCl, 20% citric acid, sat. sol. NaHCO3, sat. sol. NaCl
  3. dry with materialdried over Na2SO4
  4. customevaporated in vacuo to dryness
  5. customThe crude product was purified by gradient flash column chromatography on 230-400 mesh silica gel, utilising
  6. additiona mixture of hexane/EtOAc 1:1
  7. additiona mixture of EtOAc/MeOH 9:1 as final eluent
  8. dissolutionThe product (5.0 g) was dissolved in 100 ml of a 10% solution of diethylamine in DMF
  9. stirringstirred at room temperature for 30 minutes
  10. customThe reaction mixture was then evaporated in vacuo
  11. custompurified by gradient flash column chromatography on 230-400 mesh silica gel, utilising
  12. additiona mixture of EtOAc/MeOH 9:1
  13. additiona mixture of EtOAc/MeOH 7:3 as final eluent

Sources & evidence

ORD record
ord-c6c6167a588b499c9e74a92c5ba49a8a
Source dataset
uspto-grants-2001_08
Patent number
US06277862B1

Reaction notes

Loading…