Hydrochloric Acid → HCID 18329613, compound

HRID 2270919Notes

Reaction equation

HRID 2270919 reaction equation
[ClH:1].[C:2]([C:5]1[CH:14]=[C:13]2[C:8]([CH:9]=[CH:10][C:11]([CH2:15][N:16]([C:20]3[CH:25]=[CH:24][C:23]([N:26]4[CH2:32][CH2:31][CH2:30][NH:29][CH2:28][CH2:27]4)=[CH:22][CH:21]=3)[SH:17](=[O:19])=[O:18])=[CH:12]2)=[CH:7][CH:6]=1)(=[NH:4])[NH2:3].Cl.[C:34](=[NH:39])(OCC)[CH3:35].[CH2:40](N(CC)CC)C>C(O)C>[ClH:1].[ClH:1].[C:34]([N:29]1[CH2:30][CH2:31][CH2:32][N:26]([C:23]2[CH:22]=[CH:21][C:20]([N:16]([CH2:15][C:11]3[CH:10]=[CH:9][C:8]4[C:13](=[CH:14][C:5]([C:2](=[NH:3])[NH2:4])=[CH:6][CH:7]=4)[CH:12]=3)[S:17]([CH3:40])(=[O:18])=[O:19])=[CH:25][CH:24]=2)[CH2:27][CH2:28]1)(=[NH:39])[CH3:35]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 2724290Ethanimidic acid, ethyl ester, hydrochloride (1:1)HCID 178511908HCID 178511908, compound

Product 1

HCID 18329613HCID 18329613, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Conditions

Temperature
-20 °C

Procedure

333 mg of N-[4-(4-t-butoxycarbonylhexahydro-1H-1,4-diazepin-1-yl)phenyl]-N-[(7-cyano-2-naphthyl)-methyl]methanesulfonamide obtained in Reference Example 24 was dissolved in 10 ml of ethanol, and the resulting solution was cooled to −20° C. with stirring, into which was introduced hydrogen chloride up to saturation. The reaction mixture was stirred at 5° C. for 15 hours, and then evaporated. The resulting residue was dissolved in a mixture of 10 ml of ethanol and 10 ml of methanol, to which was added 480 mg of ammonium acetate, and stirred at room temperature for 24 hours. The reaction mixture was evaporated, and the resulting residue was purified through ODS column chromatography. From the fraction having been eluted with an eluent solvent of methanol/water (5/95), obtained was 249 mg of a roughly-purified product of N-[(7-amidino-2-naphthyl)methyl]-N-[4-(hexahydro-1H-1,4-diazepin-1-yl)phenyl]sulfonamide. 224 mg of this product was dissolved in 10 ml of ethanol, to which were added 650 mg of ethyl acetimidate hydrochloride and 683 mg of triethylamine, and stirred at room temperature for 20 hours. The reaction mixture was evaporated, and the resulting residue was purified through ODS (YMC-GEL ODS-A 120-230/70) column chromatography using an eluent solvent of methanol/water (5/95). A small amount of 1 N hydrochloric acid was added to the thus-purified product, which was then freeze-dried to obtain 169 mg of N-[4-(4-acet-imidoylhexahydro-1H-1,4-diazepin-1-yl)phenyl]-N-[(7-amidino-2-naphthyl)methyl]methanesulfonamide dihydro-chloride.

Workup

  1. stirringThe reaction mixture was stirred at 5° C. for 15 hours
  2. customevaporated
  3. dissolutionThe resulting residue was dissolved in a mixture of 10 ml of ethanol and 10 ml of methanol, to which
  4. additionwas added 480 mg of ammonium acetate
  5. stirringstirred at room temperature for 24 hours
  6. customThe reaction mixture was evaporated
  7. customthe resulting residue was purified through ODS column chromatography
  8. washFrom the fraction having been eluted with an eluent solvent of methanol/water (5/95)
  9. customobtained
  10. stirringstirred at room temperature for 20 hours
  11. customThe reaction mixture was evaporated
  12. customthe resulting residue was purified through ODS (YMC-GEL ODS-A 120-230/70) column chromatography
  13. additionA small amount of 1 N hydrochloric acid was added to the thus-purified product, which
  14. customwas then freeze-dried

Sources & evidence

ORD record
ord-12e5bf3fb63943f09e9c84bcb1c87987
Source dataset
uspto-grants-2001_12
Patent number
US06333320B1

Reaction notes

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