hydroxylamine-O-sulfonic acid → HCID 44482191, compound

HRID 2067981Notes

Reaction equation

HRID 2067981 reaction equation
COC(=O)CC[S:6]([C:9]1[CH:14]=[C:13]([CH:15]([NH:19][C:20]([C:22]2[CH:23]=[N:24][N:25]([C:28]3[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][CH:29]=3)[C:26]=2[CH3:27])=[O:21])[CH2:16][CH2:17][CH3:18])[CH:12]=[CH:11][N:10]=1)(=[O:8])=[O:7].C[O-].[Na+].[Na].[NH2:40]OS(O)(=O)=O.C([O-])(=O)C.[Na+]>CS(C)=O.CO.O.CCOC(C)=O>[S:6]([C:9]1[CH:14]=[C:13]([CH:15]([NH:19][C:20]([C:22]2[CH:23]=[N:24][N:25]([C:28]3[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][CH:29]=3)[C:26]=2[CH3:27])=[O:21])[CH2:16][CH2:17][CH3:18])[CH:12]=[CH:11][N:10]=1)(=[O:8])(=[O:7])[NH2:40]

Participants

10

Reactant 5

HCID 76284hydroxylamine-O-sulfonic acidHCID 517045Sodium AcetateHCID 5360545SodiumHCID 10942334Sodium MethoxideHCID 44481644HCID 44481644, compound

Product 1

HCID 44482191HCID 44482191, compoundYield 75%

Reagents, catalysts & solvents 4

HCID 679Dimethyl SulfoxideSolventHCID 887MethanolSolvent2×HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 3-[4-(1-{[1-(4-chloro-phenyl)-5-methyl-1H-pyrazole-4-carbonyl]-amino}-butyl)-pyridine-2-sulfonyl]-propionic acid methyl ester (60 mg, 0.12 mmol) in anhydrous DMSO (1.5 mL) is added sodium methoxide in methanol (2.7 M solution freshly prepared by dissolving 250 mg of sodium in 4.0 mL of methanol, 44 μL, 0.12 mmol). After stiffing at room temperature for 15 min, the reaction mixture is cooled to 0° C. and treated with a solution of hydroxylamine-O-sulfonic acid (260 mg, 2.3 mmol) and sodium acetate (150 mg, 1.9 mmol) in water (6 mL). The resultant mixture is warmed to room temperature and stirred overnight for 18 hours. EtOAc (100 mL) is added and the phases are separated. The organic layer is washed with water (4×15 mL, until pH of water layer is ˜5), dried over magnesium sulfate, filtered and concentrated in vacuo. The residue is purified by preparative reverse phase HPLC (eluted with 10 to 65% CH3CN/H2O and 0.1% TFA as additive) to afford 1-(4-chloro-phenyl)-5-methyl-1H-pyrazole-4-carboxylic acid [1-(2-sulfamoyl-pyridin-4-yl)-butyl]-amide (39 mg, 75%).

Workup

  1. customfreshly prepared
  2. customthe phases are separated
  3. washThe organic layer is washed with water (4×15 mL, until pH of water layer is ˜5)
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue is purified by preparative reverse phase HPLC (eluted with 10 to 65% CH3CN/H2O and 0.1% TFA as additive)

Sources & evidence

ORD record
ord-f57174a242d242ae9bdcc3c454963fa5
Source dataset
uspto-grants-2012_10
Patent number
US08293917B2

Reaction notes

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