Water → HCID 178470255, compound

HRID 2289752Notes

Reaction equation

HRID 2289752 reaction equation
Cl.Cl.[Cl:3]C1C2C(=CC(S(N(CCN(C)C)C3(C(O)=O)CCCC3)(=O)=O)=CC=2)C(NC(N)=N)=NC=1.Cl.[NH2:36][C:37]([NH2:39])=[NH:38].Cl.[CH2:41]([O:43][C:44](=[O:71])[C:45]1([CH2:70][CH2:69][CH2:68][CH2:67]1)[N:46]([S:52]([C:55]1[CH:64]=[C:63]2[C:58]([C:59]([Cl:66])=[CH:60][N:61]=[C:62]2[Cl:65])=[CH:57][CH:56]=1)(=[O:54])=[O:53])[CH2:47][CH2:48][N:49]([CH3:51])[CH3:50])[CH3:42].O>CS(C)=O>[ClH:3].[ClH:65].[CH2:41]([O:43][C:44](=[O:71])[C:45]1([CH2:70][CH2:69][CH2:68][CH2:67]1)[N:46]([S:52]([C:55]1[CH:64]=[C:63]2[C:58]([C:59]([Cl:66])=[CH:60][N:61]=[C:62]2[NH:38][C:37]([NH2:39])=[NH:36])=[CH:57][CH:56]=1)(=[O:54])=[O:53])[CH2:47][CH2:48][N:49]([CH3:51])[CH3:50])[CH3:42]

Participants

6

Reactant 4

HCID 962WaterHCID 5742Guanidine HydrochlorideHCID 86590048HCID 86590048, compoundHCID 178483755HCID 178483755, compound

Product 1

HCID 178470255HCID 178470255, compoundYield 65.6%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
50 °C

Procedure

N-[(4-Chloro-1-guanidino-7-isoquinolinyl)sulphonyl]-N-[2-(dimethylamino)ethyl]cycloleucine dihydrochloride ##STR52## NaH (32 mg, 80% dispersion by wt in mineral oil, 1.05 mmol) was added in one portion to a stirred solution of guanidine hydrochloride (145 mg, 1.52 mmol) in DMSO (4 mL) and the mixture was heated at 50° C. under N2 for 20 min. N-[(1,4-Dichloro-7-isoquinolinyl)sulphonyl]-N-[2-(dimethylamino)ethyl]cycloleucine ethyl ester hydrochloride (160 mg, 0.305 mmol) was added in one portion and the mixture heated at 90° C. for 1 h. The cooled mixture was poured into water, extracted with EtOAc (2×20 mL) and the combined organic extracts were then washed with brine, dried (Na2SO4) and evaporated in vacuo. The residue was dissolved in Et2O, filtered, and a solution of HCl in Et2O (1 M) was added which gave a precipitate. The solvents were evaporated in vacuo and the residue recrystallised from hot EtOH to give N-[(4-chloro-1-guanidino-7-isoquinolinyl)sulphonyl]-N-[2-(dimethylamino)ethyl]cycloleucine ethyl ester dihydrochloride (123 mg, 0.20 mmol) as a pale yellow solid.

Workup

  1. temperaturethe mixture heated at 90° C. for 1 h
  2. extractionextracted with EtOAc (2×20 mL)
  3. washthe combined organic extracts were then washed with brine
  4. dry with materialdried (Na2SO4)
  5. customevaporated in vacuo
  6. dissolutionThe residue was dissolved in Et2O
  7. filtrationfiltered
  8. additiona solution of HCl in Et2O (1 M) was added which
  9. customgave a precipitate
  10. customThe solvents were evaporated in vacuo
  11. customthe residue recrystallised from hot EtOH

Sources & evidence

ORD record
ord-d323600c88b3469eb13d8f7afe00b130
Source dataset
uspto-grants-2000_07
Patent number
US06093731

Reaction notes

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