Diisopropylethylamine → methyl (S)-2-(4-ethylpiperazin-1-yl)-3-[4-(2-methyl-quinolin-4-ylmethoxy)benzoylamino]propanoate

HRID 517522Notes

Reaction equation

HRID 517522 reaction equation
[CH3:1][C:2]1[CH:11]=[C:10]([CH2:12][O:13][C:14]2[CH:22]=[CH:21][C:17]([C:18](O)=[O:19])=[CH:16][CH:15]=2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1.F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C.Cl.Cl.Cl.[NH2:57][CH2:58][CH:59]([N:64]1[CH2:69][CH2:68][N:67]([CH2:70][CH3:71])[CH2:66][CH2:65]1)[C:60]([O:62][CH3:63])=[O:61].C(=O)([O-])O.[Na+]>CN(C)C=O>[CH2:70]([N:67]1[CH2:66][CH2:65][N:64]([C@@H:59]([CH2:58][NH:57][C:18](=[O:19])[C:17]2[CH:21]=[CH:22][C:14]([O:13][CH2:12][C:10]3[C:9]4[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=4)[N:3]=[C:2]([CH3:1])[CH:11]=3)=[CH:15][CH:16]=2)[C:60]([O:62][CH3:63])=[O:61])[CH2:69][CH2:68]1)[CH3:71]

Participants

7

Reactant 5

HCID 81531Diisopropylethylamine2×HCID 516892Sodium BicarbonateHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 220327754-[(2-Methylquinolin-4-yl)methoxy]benzoic acidHCID 67056995Methyl 3-amino-2-(4-ethylpiperazin-1-yl)propanoate trihydrochloride

Product 1

HCID 67057014methyl (S)-2-(4-ethylpiperazin-1-yl)-3-[4-(2-methyl-quinolin-4-ylmethoxy)benzoylamino]propanoateYield 81.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

0.6 g (2.1 mmol) of 4-(2-methylquinolin-4-ylmethoxy)benzoic acid are dissolved in 10 ml of dimethylformamide then 0.7 g (2.3 mmol) of O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate and 1.1 ml (6.3 mmol) of diisopropylethylamine are added. After stirring for 15 minutes at ambient temperature, a solution of 700 mg (2.1 mmol) of methyl 3-amino-2-(4-ethylpiperazin-1-yl)propanoate trihydrochloride and 1.1 ml (6.3 mmol) of diisopropylethylamine in 10 ml of dimethylformamide is added. The reaction medium is stirred at ambient temperature for 18 h then is hydrolysed with a saturated aqueous solution of sodium hydrogen carbonate. After extraction with ethyl acetate, the organic phase is washed with a saturated aqueous solution of sodium hydrogen carbonate then with a saturated aqueous solution of sodium chloride, dried over magnesium sulphate, filtered and concentrated under vacuum. The product is purified by chromatography over silica gel eluted with a 93/7 dichloromethane/methanol mixture to give 840 mg (81%) of methyl (S)-2-(4-ethylpiperazin-1-yl)-3-[4-(2-methylquinolin-4-ylmethoxy)benzoylamino]propanoate in the form of a colourless oil.

Workup

  1. stirringThe reaction medium is stirred at ambient temperature for 18 h
  2. extractionAfter extraction with ethyl acetate
  3. washthe organic phase is washed with a saturated aqueous solution of sodium hydrogen carbonate
  4. dry with materialwith a saturated aqueous solution of sodium chloride, dried over magnesium sulphate
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum
  7. customThe product is purified by chromatography over silica gel
  8. washeluted with a 93/7 dichloromethane/methanol mixture

Sources & evidence

ORD record
ord-3eeafe58e663433998154e1ec6f30cf5
Source dataset
uspto-grants-2015_08
Patent number
US09115102B2

Reaction notes

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