Cesium carbonate → methyl (S)-2-(4-methane-sulphonylpiperazin-1-yl)-3-[4-(pyridin-4-ylmethoxy)-benzoylamino]propanoate

HRID 517515Notes

Reaction equation

HRID 517515 reaction equation
C(=O)([O-])[O-].[Cs+].[Cs+].Cl.Cl[CH2:9][C:10]1[CH:15]=[CH:14][N:13]=[CH:12][CH:11]=1.[OH:16][C:17]1[CH:41]=[CH:40][C:20]([C:21]([NH:23][CH2:24][C@H:25]([N:30]2[CH2:35][CH2:34][N:33]([S:36]([CH3:39])(=[O:38])=[O:37])[CH2:32][CH2:31]2)[C:26]([O:28][CH3:29])=[O:27])=[O:22])=[CH:19][CH:18]=1>CN(C)C=O>[CH3:39][S:36]([N:33]1[CH2:32][CH2:31][N:30]([C@@H:25]([CH2:24][NH:23][C:21](=[O:22])[C:20]2[CH:19]=[CH:18][C:17]([O:16][CH2:9][C:10]3[CH:15]=[CH:14][N:13]=[CH:12][CH:11]=3)=[CH:41][CH:40]=2)[C:26]([O:28][CH3:29])=[O:27])[CH2:35][CH2:34]1)(=[O:37])=[O:38]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 745704-(Chloromethyl)pyridinium chlorideHCID 67056914methyl (S)-3-(4-hydroxybenzoylamino)-2-(4-methanesulphonylpiperazin-1-yl)propanoate

Product 1

HCID 86667911methyl (S)-2-(4-methane-sulphonylpiperazin-1-yl)-3-[4-(pyridin-4-ylmethoxy)-benzoylamino]propanoateYield 64.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

1 g (3.2 mmol) of caesium carbonate and 280 mg (1.7 mmol) of 4-chloromethylpyridine hydrochloride are added to a solution of 560 mg (1.4 mmol) of methyl (S)-3-(4-hydroxybenzoylamino)-2-(4-methanesulphonylpiperazin-1-yl)propanoate (prepared as described in example 4-4) diluted in 20 ml of dimethylformamide. The reaction medium is stirred at 80° C. for 24 h. The reaction medium is cooled, hydrolysed and extracted with ethyl acetate. The organic phase is washed once with water and once with a saturated aqueous solution of sodium chloride, dried over magnesium sulphate, filtered and concentrated under vacuum. The crude product is purified by chromatography over silica gel eluted with a 30/70 heptane/ethyl acetate mixture+10% methanol. 430 mg (62%) of methyl (S)-2-(4-methane-sulphonylpiperazin-1-yl)-3-[4-(pyridin-4-ylmethoxy)-benzoylamino]propanoate are obtained in the form of a white solid.

Workup

  1. temperatureThe reaction medium is cooled
  2. extractionhydrolysed and extracted with ethyl acetate
  3. washThe organic phase is washed once with water and once with a saturated aqueous solution of sodium chloride
  4. dry with materialdried over magnesium sulphate
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum
  7. customThe crude product is purified by chromatography over silica gel
  8. washeluted with a 30/70 heptane/ethyl acetate mixture+10% methanol

Sources & evidence

ORD record
ord-5042df7fa38d453ba1b8435ce9a235ef
Source dataset
uspto-grants-2015_08
Patent number
US09115102B2

Reaction notes

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