Triethylamine → methyl (S)-2-(4-methanesulphonylpiperazin-1-yl)-3-[4-(2-methoxyethoxymethoxy)benzoyl-amino]propanoate

HRID 517504Notes

Reaction equation

HRID 517504 reaction equation
[CH3:1][O:2][CH2:3][CH2:4][O:5][CH2:6][O:7][C:8]1[CH:16]=[CH:15][C:11]([C:12]([OH:14])=O)=[CH:10][CH:9]=1.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.Cl.[NH2:40][CH2:41][C@H:42]([N:47]1[CH2:52][CH2:51][N:50]([S:53]([CH3:56])(=[O:55])=[O:54])[CH2:49][CH2:48]1)[C:43]([O:45][CH3:46])=[O:44].C(N(CC)CC)C.C(=O)([O-])O.[Na+]>CN(C)C=O>[CH3:56][S:53]([N:50]1[CH2:49][CH2:48][N:47]([C@@H:42]([CH2:41][NH:40][C:12](=[O:14])[C:11]2[CH:10]=[CH:9][C:8]([O:7][CH2:6][O:5][CH2:4][CH2:3][O:2][CH3:1])=[CH:16][CH:15]=2)[C:43]([O:45][CH3:46])=[O:44])[CH2:52][CH2:51]1)(=[O:54])=[O:55]

Participants

8

Reactant 6

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 149522434-(2-Methoxyethoxymethoxy)benzoic acidHCID 67057002methyl (S)-3-amino-2-(4-methanesulphonylpiperazin-1-yl)propanoate hydrochloride

Product 1

HCID 67056964methyl (S)-2-(4-methanesulphonylpiperazin-1-yl)-3-[4-(2-methoxyethoxymethoxy)benzoyl-amino]propanoateYield 68%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

1.1 g (5 mmol) of 4-(2-methoxyethoxymethoxy)benzoic acid are put into solution in 15 ml of dimethylformamide then 0.7 g (5.5 mmol) of 1-hydroxybenzotriazole and 1.1 g (5.5 mmol) of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride are added. The reaction medium is stirred for 20 minutes before adding a mixture of 1.5 g (5 mmol) of methyl (S)-3-amino-2-(4-methanesulphonylpiperazin-1-yl)propanoate hydrochloride (prepared as described in 2-3) and of 1.4 ml (9.9 mmol) of triethylamine in 15 ml of dimethylformamide. The reaction medium is stirred at 50° C. for 1 h 30 min then at ambient temperature for 18 h. After hydrolysis with a saturated aqueous solution of sodium hydrogen carbonate then extraction with ethyl acetate, the organic phase is washed with an aqueous solution of sodium hydrogen carbonate then with a saturated aqueous solution of sodium chloride, dried over magnesium sulphate, filtered and concentrated. The crude product obtained is purified by chromatography over silica gel eluted with a 9/1 dichloromethane/methanol mixture. 1.6 g (68%) of methyl (S)-2-(4-methanesulphonylpiperazin-1-yl)-3-[4-(2-methoxyethoxymethoxy)benzoylamino]propanoate are obtained in the form of a colourless oil.

Workup

  1. additionbefore adding
  2. stirringThe reaction medium is stirred at 50° C. for 1 h 30 min
  3. waitat ambient temperature for 18 h
  4. extractionextraction with ethyl acetate
  5. washthe organic phase is washed with an aqueous solution of sodium hydrogen carbonate
  6. dry with materialwith a saturated aqueous solution of sodium chloride, dried over magnesium sulphate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude product obtained
  10. customis purified by chromatography over silica gel
  11. washeluted with a 9/1 dichloromethane/methanol mixture

Sources & evidence

ORD record
ord-b506e38127ba4bb9927166c70c94864b
Source dataset
uspto-grants-2015_08
Patent number
US09115102B2

Reaction notes

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