Hydrochloric Acid → 2-[5-(5-chloro-1,3-dimethyl-1H-pyrazole-4-sulfonylamino)-pyridin-2-yl]-malonic acid dibenzyl ester

HRID 858067Notes

Reaction equation

HRID 858067 reaction equation
[CH2:1]([O:8][C:9](=[O:28])[CH:10]([C:21]1[CH:26]=[CH:25][C:24]([NH2:27])=[CH:23][N:22]=1)[C:11]([O:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl:29][C:30]1[N:34]([CH3:35])[N:33]=[C:32]([CH3:36])[C:31]=1[S:37](Cl)(=[O:39])=[O:38].Cl>N1C=CC=CC=1>[CH2:1]([O:8][C:9](=[O:28])[CH:10]([C:21]1[CH:26]=[CH:25][C:24]([NH:27][S:37]([C:31]2[C:32]([CH3:36])=[N:33][N:34]([CH3:35])[C:30]=2[Cl:29])(=[O:38])=[O:39])=[CH:23][N:22]=1)[C:11]([O:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 27771265-chloro-1,3-dimethyl-1H-pyrazole-4-sulfonyl chlorideHCID 691148292-(5-Amino-pyridin-2-yl)-malonic acid dibenzyl ester

Product 1

HCID 691152402-[5-(5-chloro-1,3-dimethyl-1H-pyrazole-4-sulfonylamino)-pyridin-2-yl]-malonic acid dibenzyl esterYield 55%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
25 °C

Procedure

A solution of 2-(5-amino-pyridin-2-yl)-malonic acid dibenzyl ester in pyridine cooled to 0° C. was treated with 5-chloro-1,3-dimethyl-1H-pyrazole-4-sulfonyl chloride. The reaction mixture was allowed to slowly warm to 25° C. and was stirred at 25° C. for 24 h. At this time, the reaction mixture was cooled to 0° C. and acidified to pH=1 with 3.0M aqueous hydrochloric acid solution. The resulting mixture was extracted with ethyl acetate. The organics were washed with a 1.0M aqueous hydrochloric acid solution, water, and a saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230–400 mesh, 65/35 ethyl acetate/hexanes) afforded 2-[5-(5-chloro-1,3-dimethyl-1H-pyrazole-4-sulfonylamino)-pyridin-2-yl]-malonic acid dibenzyl ester (55%) as a colorless solid; LRMS for C27H25ClN4O6S (M+H)+ at m/z=569/571.

Workup

  1. temperatureAt this time, the reaction mixture was cooled to 0° C.
  2. extractionThe resulting mixture was extracted with ethyl acetate
  3. washThe organics were washed with a 1.0M aqueous hydrochloric acid solution, water
  4. dry with materiala saturated aqueous sodium chloride solution, dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-bc67c1acefd643bd8a10966db6630424
Source dataset
uspto-grants-2006_12
Patent number
US07148229B2

Reaction notes

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