Sodium Bicarbonate → 3-[5-(1-{[1-(4-chloro-phenyl)-5-methyl-1H-pyrazole-4-carbonyl]-amino}-butyl)-pyridine-3-sulfonyl]-propionic acid methyl ester

HRID 2067977Notes

Reaction equation

HRID 2067977 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:8]([NH:12][C:13]([C:15]2[CH:16]=[N:17][N:18]([C:21]3[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][CH:22]=3)[C:19]=2[CH3:20])=[O:14])[CH2:9][CH2:10][CH3:11])[CH:5]=[N:6][CH:7]=1.[CH3:28][O:29][C:30](=[O:36])[CH2:31][CH2:32][S:33]([O-:35])=[O:34].[Na+].[Cl-].[NH4+].[Na].C(=O)(O)[O-].[Na+]>CS(C)=O.[Cu]I>[N:6]1[CH:7]=[CH:2][CH:3]=[C:4]([CH:8]([NH:12][C:13]([C:15]2[CH:16]=[N:17][N:18]([C:21]3[CH:22]=[CH:23][C:24]([Cl:27])=[CH:25][CH:26]=3)[C:19]=2[CH3:20])=[O:14])[CH2:9][CH2:10][CH3:11])[CH:5]=1.[CH3:28][O:29][C:30](=[O:36])[CH2:31][CH2:32][S:33]([C:2]1[CH:7]=[N:6][CH:5]=[C:4]([CH:8]([NH:12][C:13]([C:15]2[CH:16]=[N:17][N:18]([C:21]3[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][CH:22]=3)[C:19]=2[CH3:20])=[O:14])[CH2:9][CH2:10][CH3:11])[CH:3]=1)(=[O:35])=[O:34]

Participants

8

Reactant 4

HCID 516892Sodium BicarbonateHCID 23665669Sodium 1-Methyl 3-SulfinopropionateHCID 444805971-(4-Chloro-phenyl)-5-methyl-1H-pyrazole-4-carboxylic acid [1-(5-bromo-pyridin-3-yl)-butyl]-amideHCID 86657765Sodium ammonium chloride

Product 2

HCID 444808683-[5-(1-{[1-(4-chloro-phenyl)-5-methyl-1H-pyrazole-4-carbonyl]-amino}-butyl)-pyridine-3-sulfonyl]-propionic acid methyl esterYield 42%HCID 444813731-(4-chloro-phenyl)-5-methyl-1H-pyrazole-4-carboxylic acid (1-pyridin-3-yl-butyl)-amideYield 16%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolvent

Procedure

A solution of 1-(4-chloro-phenyl)-5-methyl-1H-pyrazole-4-carboxylic acid [1-(5-bromo-pyridin-3-yl)-butyl]-amide (1.1 g, 2.5 mmol), copper(I) iodide (1.4 g, 7.4 mmol), sodium 3-methoxy-3-oxopropane-1-sulfinate (1.3 g, 7.4 mmol) in DMSO (10 mL) is heated at 130° C. for 1.5 hour. After cooling to room temperature, saturated aqueous sodium ammonium chloride (10 mL) is added and the resultant mixture is stirred for 1 hour. The crude mixture is poured into saturated aqueous sodium bicarbonate (250 mL) and extracted with EtOAc (1×250 mL, 2×100 mL). The combined organic layers are washed with brine (100 mL), dried over sodium sulfate, filtered and concentrated in vacuo. Purification by flash chromatography on silica gel (eluted with 25 to 75% EtOAc/hexanes) affords 1-(4-chloro-phenyl)-5-methyl-1H-pyrazole-4-carboxylic acid (1-pyridin-3-yl-butyl)-amide (159 mg, 16%) and 3-[5-(1-{[1-(4-chloro-phenyl)-5-methyl-1H-pyrazole-4-carbonyl]-amino}-butyl)-pyridine-3-sulfonyl]-propionic acid methyl ester (540 mg, 42%).

Workup

  1. extractionextracted with EtOAc (1×250 mL, 2×100 mL)
  2. washThe combined organic layers are washed with brine (100 mL)
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customPurification by flash chromatography on silica gel (eluted with 25 to 75% EtOAc/hexanes)

Sources & evidence

ORD record
ord-bbad6508b3f248269bb1ef59fe53c507
Source dataset
uspto-grants-2012_10
Patent number
US08293917B2

Reaction notes

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