Hydrochloric Acid → HCID 21993803, compound

HRID 1978445Notes

Reaction equation

HRID 1978445 reaction equation
[N:1]1[CH:2]=[C:3]2[N:12]3[C:7](=[CH:8][CH:9]=[CH:10][C:11]=13)[S:6][C:5]([C:13]([OH:15])=O)=[CH:4]2.ON1C(=O)CCC1=O.[ClH:24].C(N=C=NCCCN(C)C)C.[NH2:36][CH2:37][CH2:38][N:39](C(OC(C)(C)C)=O)[CH2:40][CH2:41][CH2:42][C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1.Cl>C(#N)C.C(OCC)C.C(O)C.C(N(CC)CC)C>[ClH:24].[ClH:24].[C:43]1([CH2:42][CH2:41][CH2:40][NH:39][CH2:38][CH2:37][NH:36][C:13]([C:5]2[S:6][C:7]3[N:12]4[C:3](=[CH:2][N:1]=[C:11]4[CH:10]=[CH:9][CH:8]=3)[CH:4]=2)=[O:15])[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 80170N-HydroxysuccinimideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 10943925HCID 10943925, compoundHCID 21993855HCID 21993855, compound

Product 1

HCID 21993803HCID 21993803, compound

Reagents, catalysts & solvents 4

HCID 702EthanolSolventHCID 3283Diethyl EtherSolventHCID 6342AcetonitrileSolvent2×HCID 8471TriethylamineSolvent

Procedure

To a suspension of 1.09 g (ca 3.2 mM) of 5-thia-1,8b-diazaacenaphthylene-4-carboxylic acid and 1.15 g (10 mM) of N-hydroxysuccinimide in acetonitrile (15 ml) was added 1.92 g (10 mM) of N-ethyl-N′-3-(N,N-dimethylamino)propylcarbodiimide hydrochloride at room temperature, and the mixture was stirred for 2 hours. The solvent was then distilled off under reduced pressure and the residue was diluted with water and extracted with chloroform. The organic layer was washed with saturated aqueous solution of sodium chloride and dried over MgSO4 and the solvent was distilled off under reduced pressure to provide a crude active ester (1.63 g). To a solution of this crude active ester (1.63 g) and 1.4 ml (10 mM) of triethylamine in acetonitrile (15 ml) was added 1.67 g (6.00 mM) of tert-butyl N-(2-aminoethan-1-yl)-3-phenylpropan-1-ylaminocarboxylate at room temperature, and the mixture was stirred at room temperature for 1 hour. The solvent was then distilled off under reduced pressure and the residue was diluted with water and extracted with methylene chloride. The organic layer was washed with saturated aqueous solution of sodium chloride and dried over MgSO4 and the solvent was distilled off under reduced pressure. The crude residue was subjected to column chromatography (methanol/ethyl acetate 10%), whereby a crude product (2.13 g, containing impurities) was obtained. To 413 mg (0.80 mM) of this crude product was added 1.5 ml (18 mM) of 12N-hydrochloric acid, and the mixture was stirred for several minutes. Then, ethanol and diethyl ether were added to the reaction mixture and the resulting crystals were collected by filtration and rinsed serially with ethanol, acetone, and diethyl ether to provide the title compound.

Workup

  1. distillationThe solvent was then distilled off under reduced pressure
  2. additionthe residue was diluted with water
  3. extractionextracted with chloroform
  4. washThe organic layer was washed with saturated aqueous solution of sodium chloride
  5. dry with materialdried over MgSO4
  6. distillationthe solvent was distilled off under reduced pressure
  7. customto provide a crude active ester (1.63 g)
  8. stirringthe mixture was stirred at room temperature for 1 hour
  9. distillationThe solvent was then distilled off under reduced pressure
  10. additionthe residue was diluted with water
  11. extractionextracted with methylene chloride
  12. washThe organic layer was washed with saturated aqueous solution of sodium chloride
  13. dry with materialdried over MgSO4
  14. distillationthe solvent was distilled off under reduced pressure
  15. customwas obtained
  16. stirringthe mixture was stirred for several minutes
  17. filtrationthe resulting crystals were collected by filtration
  18. washrinsed serially with ethanol, acetone, and diethyl ether

Sources & evidence

ORD record
ord-4a4f070d036b45aca510816f2bb6e8e4
Source dataset
uspto-grants-2001_05
Patent number
US06235731B1

Reaction notes

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