Ethanol → HCID 44481643, compound

HRID 2067980Notes

Reaction equation

HRID 2067980 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].CC1C=CC(S(NCl)(=O)=O)=CC=1.[CH3:52][NH2:53].C(O)C>C1COCC1.CO.C(=O)(O)[O-].[Na+].O>[CH3:52][NH:53][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:7])=[O:8]

Participants

11

Reactant 6

HCID 702EthanolHCID 6329MethylamineHCID 31388TosylchloramideHCID 5360545SodiumHCID 10942334Sodium MethoxideHCID 44481644HCID 44481644, compound

Product 1

HCID 44481643HCID 44481643, compoundYield 90%

Reagents, catalysts & solvents 4

HCID 887MethanolSolvent2×HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 516892Sodium BicarbonateSolvent

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 (200 mg, 0.39 mmol) in anhydrous THF (10 mL) is added sodium methoxide in methanol (2.6 M solution freshly prepared by dissolving 140 mg of sodium in 2.4 mL of methanol, 0.15 mL, 0.39 mmol). After stirring at room temperature for 10 min, the reaction mixture is concentrated in vacuo. Anhydrous THF (10 mL) is added and the concentration process is repeated. The resultant residue is dried under high vacuum for 5 min, dissolved in THF (10 mL) and treated with chloramine T (180 mg, 0.77 mmol). The reaction mixture is stirred at room temperature for 15 min and then treated with methyl amine in ethanol (33% solution in ethanol, 0.48 mL, 3.9 mmol) in one portion. After 20 min the reaction mixture is diluted with saturated aqueous sodium bicarbonate (20 mL) and water (8 mL), and extracted with EtOAc (2×35 mL). The combined organic layers are washed with brine (10 mL), dried over sodium sulfate, filtered and concentrated in vacuo. The residue is purified by preparative reverse phase HPLC (eluted with 10 to 90% CH3CN/H2O and 0.1% TFA as additive) to afford 1-(4-chloro-phenyl)-5-methyl-1H-pyrazole-4-carboxylic acid [1-(2-methylsulfamoyl-pyridin-4-yl)-butyl]-amide (160 mg, 90%).

Workup

  1. customfreshly prepared
  2. concentrationthe reaction mixture is concentrated in vacuo
  3. additionAnhydrous THF (10 mL) is added
  4. dry with materialThe resultant residue is dried under high vacuum for 5 min
  5. dissolutiondissolved in THF (10 mL)
  6. stirringThe reaction mixture is stirred at room temperature for 15 min
  7. extractionextracted with EtOAc (2×35 mL)
  8. washThe combined organic layers are washed with brine (10 mL)
  9. dry with materialdried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customThe residue is purified by preparative reverse phase HPLC (eluted with 10 to 90% CH3CN/H2O and 0.1% TFA as additive)

Sources & evidence

ORD record
ord-9aed5dd1224d4fa89a0a38582f856915
Source dataset
uspto-grants-2012_10
Patent number
US08293917B2

Reaction notes

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