Methyl 3-chlorocarbonylpropenoate → (S,E)-N-(a-ethylbenzyl)-3-[2-(3-methoxycarbonylpropenoyl)aminoethoxy]-2-phenylquinoline-4-carboxamide

HRID 651067Notes

Reaction equation

HRID 651067 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].Cl[C:34]([CH:36]=[CH:37][C:38]([O:40][CH3:41])=[O:39])=[O:35]>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:34](=[O:35])/[CH:36]=[CH:37]/[C:38]([O:40][CH3:41])=[O:39])=[O:12])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)[CH3:2]

Participants

4

Reactant 2

HCID 574607Methyl 3-chlorocarbonylpropenoateHCID 10764865(S)-N-(alpha-ethylbenzyl)-3-(2-aminoethoxy)-2-phenylquinoline-4-carboxamide

Product 1

HCID 70250562(S,E)-N-(a-ethylbenzyl)-3-[2-(3-methoxycarbonylpropenoyl)aminoethoxy]-2-phenylquinoline-4-carboxamideYield 16.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

1.4 g (3.3 mmol) of (S)-N-(α-ethylbenzyl)-3-(2-aminoethoxy)-2-phenylquinoline-4-carboxamide (compound of Description 4) were dissolved, under nitrogen atmosphere, in 35 ml of dry CH2Cl2; 0.77 ml (5.5 mmol) of TEA were added, the solution was cooled to 0° C. and 0.4 g (3.4 mmol) of methyl 3-chlorocarbonylpropenoate (compound of Description 5), dissolved in 25 ml of CH2Cl2, were added dropwise. The reaction was stirred at room temperature for 2 days, washed with H2O, 20% citric acid, sat. sol. NaHCO3, sat. sol. NaCl, dried over Na2SO4 and evaporated in vacuo to dryness. The residue was purified by gradient flash column chromatography on 230-400 mesh silica utilising a mixture of hexane/EtOAc 8:2 as starting eluent and a mixture of hexane/EtOAc 3:7 as final eluent. The crude product so obtained was further purified by preparative HPLC to yield 0.30 g of the title compound.

Workup

  1. additionwere added dropwise
  2. washwashed with H2O, 20% citric acid, sat. sol. NaHCO3, sat. sol. NaCl
  3. dry with materialdried over Na2SO4
  4. customevaporated in vacuo to dryness
  5. customThe residue was purified by gradient flash column chromatography on 230-400 mesh silica utilising
  6. additiona mixture of hexane/EtOAc 8:2
  7. additiona mixture of hexane/EtOAc 3:7 as final eluent
  8. customThe crude product so obtained
  9. customwas further purified by preparative HPLC

Sources & evidence

ORD record
ord-d367e0593372498aa139618be9511794
Source dataset
uspto-grants-2001_08
Patent number
US06277862B1

Reaction notes

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