Hydrochloric Acid → (2S)-3-{[(3-chloro-4-methyl-5-sulfophenyl)carbamoyl]amino}-2-(methylamino)propanoic acid

HRID 1773100Notes

Reaction equation

HRID 1773100 reaction equation
[CH:1]1[N:5]=[CH:4][N:3]([C:6]([N:8]2C=N[CH:10]=[CH:9]2)=[O:7])[CH:2]=1.NC1[CH:15]=[C:16]([Cl:25])[C:17]([CH3:24])=[C:18]([S:20]([OH:23])(=[O:22])=[O:21])C=1.Cl.[N+](C1C=CC=CC=1S(Cl)(=O)=O)([O-])=O.[C:40](=O)([O-:42])[O-:41].[K+].[K+].CI.FC(F)(F)C(O)=O>C(#N)C.CN(C=O)C.C(N(CC)CC)C.C(Cl)Cl.O1CCOCC1>[Cl:25][C:16]1[CH:15]=[C:9]([NH:8][C:6]([NH:3][CH2:2][C@H:1]([NH:5][CH3:4])[C:40]([OH:42])=[O:41])=[O:7])[CH:10]=[C:18]([S:20]([OH:23])(=[O:22])=[O:21])[C:17]=1[CH3:24]

Participants

13

Reactant 7

HCID 313Hydrochloric AcidHCID 6328Methyl iodideHCID 6422Trifluoroacetic acidHCID 11430Potassium CarbonateHCID 155402-Nitrobenzenesulfonyl chlorideHCID 682631,1'-CarbonyldiimidazoleHCID 808054-Amino-6-chlorotoluene-2-sulphonic acid

Product 1

HCID 86679037(2S)-3-{[(3-chloro-4-methyl-5-sulfophenyl)carbamoyl]amino}-2-(methylamino)propanoic acid

Reagents, catalysts & solvents 5

HCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolventHCID 8471TriethylamineSolventHCID 312751,4-DioxaneSolvent2×

Procedure

100 mg of Boc-DAP-OtBu hydrochloride and 60 mg of CDI were dissolved in 1 ml of acetonitrile and stirred for 5 minutes. 75 mg of 5-amino-3-chloro-2-methylbenzenesulfonic acid was added and stirred overnight. Extraction was performed with ethyl acetate to obtain a crude product. The obtained crude product was added with 1.5 ml of dioxane and 0.5 ml of dioxane solution containing 4N hydrochloric acid and stirred for 2 hours. The solvent was distilled away to obtain a crude product. To the obtained crude product, 2 ml of methylene chloride was added, and 52 mg of 2-nitrobenzenesulfonyl chloride and 0.14 ml of triethylamine were added. After 2 hours of agitation, extraction was performed with ethyl acetate to obtain a crude product. The obtained crude product was added with 50 mg of potassium carbonate, 2 ml of DMF and 0.1 ml of methyl iodide and stirred at room temperature overnight. Following extraction with ethyl acetate, the solvent was distilled away to obtain a crude product. The obtained crude product was added with 3 ml of trifluoroacetic acid and stirred at room temperature for 5 hours. The solvent was distilled away and the residue was lyophilized. The resulting lyophilized product was added with 1 ml of DMF, further added with 54 μl of 1-dodecanethiol and 80 μl of a 28% sodium ethoxide ethanol solution, and stirred at room temperature. Following dilution with water and acetonitrile, purification was performed using purification step A to obtain the title compound.

Workup

  1. stirringstirred overnight
  2. extractionExtraction
  3. customto obtain a crude product
  4. customThe obtained crude product
  5. stirringstirred for 2 hours
  6. distillationThe solvent was distilled away
  7. customto obtain a crude product
  8. additionwas added
  9. extractionAfter 2 hours of agitation, extraction
  10. customto obtain a crude product
  11. customThe obtained crude product
  12. stirringstirred at room temperature overnight
  13. extractionextraction with ethyl acetate
  14. distillationthe solvent was distilled away
  15. customto obtain a crude product
  16. customThe obtained crude product
  17. stirringstirred at room temperature for 5 hours
  18. distillationThe solvent was distilled away
  19. additionThe resulting lyophilized product was added with 1 ml of DMF
  20. additionfurther added with 54 μl of 1-dodecanethiol and 80 μl of a 28% sodium ethoxide ethanol solution
  21. stirringstirred at room temperature
  22. customwith water and acetonitrile, purification
  23. custompurification step A

Sources & evidence

ORD record
ord-bd734f2356244825b6e092400130c010
Source dataset
uspto-grants-2016_02
Patent number
US09253997B2

Reaction notes

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