Hydrochloric Acid → N-(4-iso-propylbenzenesulfonyl)-alpha-(4-cyano-2-n-propylphenoxy)-3,4-methylenedioxyphenyl-acetamide

HRID 1378879Notes

Reaction equation

HRID 1378879 reaction equation
C[C:2]([C:18]1[CH:23]=[CH:22][C:21]2[O:24][CH2:25][O:26][C:20]=2[CH:19]=1)([O:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]#[N:14])=[CH:9][C:8]=1[CH2:15][CH2:16][CH3:17])[C:3](O)=[O:4].Cl.CN(C)CCCN=C=NCC.[CH:39]([C:42]1[CH:47]=[CH:46][C:45]([S:48]([NH2:51])(=[O:50])=[O:49])=[CH:44][CH:43]=1)([CH3:41])[CH3:40].C(Cl)(Cl)Cl.CO.[OH-].[NH4+].Cl>C(Cl)Cl.CN(C)C1C=CN=CC=1>[CH:39]([C:42]1[CH:43]=[CH:44][C:45]([S:48]([NH:51][C:3](=[O:4])[CH:2]([C:18]2[CH:23]=[CH:22][C:21]3[O:24][CH2:25][O:26][C:20]=3[CH:19]=2)[O:6][C:7]2[CH:12]=[CH:11][C:10]([C:13]#[N:14])=[CH:9][C:8]=2[CH2:15][CH2:16][CH3:17])(=[O:49])=[O:50])=[CH:46][CH:47]=1)([CH3:41])[CH3:40]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 2323144-(1-Methylethyl)benzenesulfonamideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 21873181Chloroform methanol ammonium hydroxideHCID 22912495Methyl alpha-(2-n-propyl-4-cyanophenoxy)-3,4-methylenedioxyphenylacetic acid

Product 1

HCID 22912486N-(4-iso-propylbenzenesulfonyl)-alpha-(4-cyano-2-n-propylphenoxy)-3,4-methylenedioxyphenyl-acetamideYield 38%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 2.92 g (8.61 mmol) of the product of Step D in 40 mL of methylene chloride was added 2.31 g (12.05 mmol) of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, 1.26 g (10.33 mmol) of 4-dimethylaminopyridine, and 1.89 g (9.47 mmol) of 4-iso-propylbenzenesulfonamide. The reaction mixture was stirred overnight and after TLC analysis (80:15:1 chloroform/methanol/ammonium hydroxide) was poured into 1N HCl and extracted with ethyl acetate. The extract was washed with brine, dried over magnesium sulfate, filtered, and evaporated in vacuo. The residue was partially purified with silica gel flash chromatography eluting first with 40% ethyl acetate-hexane and then with 3% methanolmethylene chloride to flush the column. All of the product fractions were contaminated and were chromatographed. The 3.86 g of semipurified material was dissolved in 15 mL of acetonitrile and 15 mL of water and filtered through a 0.45 μM membrane filter. The compound was purified using a Waters Delta Prep 3000 HPLC by applying the filtered solution to an M1000 Prep-Pak module containing a 47×300 mm 15 mM DeltaPak C18 column and eluting at 50 mL/min first using 50% A (95-5 acetonitrile-water) and 50% B (95-5 water-acetonitrile) with 0.1% TFA for 15 minutes and then 70% A (95-5 acetonitrile-water) and 30% B (95-5 water-acetonitrile) both with 0.1% TFA. The column effluent was monitored simultaneously at 210 and 277 nM with a Waters model 490 UV-visible detector and the purified fractions were combined in a round bottom flask and concentrated in vacuo to afford 1.45 g (38%) of the title compound as an amorphous solid.

Workup

  1. extractionextracted with ethyl acetate
  2. washThe extract was washed with brine
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. customevaporated in vacuo
  6. customThe residue was partially purified with silica gel flash chromatography
  7. washeluting first with 40% ethyl acetate-hexane
  8. customwith 3% methanolmethylene chloride to flush the column
  9. customwere chromatographed
  10. dissolutionThe 3.86 g of semipurified material was dissolved in 15 mL of acetonitrile
  11. filtration15 mL of water and filtered through a 0.45 μM membrane
  12. filtrationfilter
  13. customThe compound was purified
  14. additioncontaining a 47×300 mm 15 mM DeltaPak C18 column
  15. washeluting at 50 mL/min
  16. customfor 15 minutes
  17. customthe purified fractions were combined in a round bottom flask
  18. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-853b1bfe90184ac296f89442829f2d38
Source dataset
uspto-grants-1997_09
Patent number
US05668176

Reaction notes

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