Guanidine Hydrochloride → HCID 178470523, compound

HRID 2289749Notes

Reaction equation

HRID 2289749 reaction equation
FC(F)(F)C(O)=O.ClC1C2C(=CC(S(NC3(C(O)=O)CCCC3)(=O)=O)=CC=2)C(NC(N)=N)=NC=1.Cl.NC(N)=N.[CH2:40]([O:42][C:43](=[O:69])[C:44]1([CH2:68][CH2:67][CH2:66][CH2:65]1)[NH:45][S:46]([C:49]1[CH:58]=[C:57]2[C:52]([C:53]([Cl:64])=[CH:54][NH:55][C:56]2(Cl)[NH:59][C:60]([NH2:62])=[NH:61])=[CH:51][CH:50]=1)(=[O:48])=[O:47])[CH3:41]>CS(C)=O>[CH2:40]([O:42][C:43](=[O:69])[C:44]1([CH2:65][CH2:66][CH2:67][CH2:68]1)[NH:45][S:46]([C:49]1[CH:58]=[C:57]2[C:52]([C:53]([Cl:64])=[CH:54][N:55]=[C:56]2[NH:59][C:60]([NH2:62])=[NH:61])=[CH:51][CH:50]=1)(=[O:47])=[O:48])[CH3:41]

Participants

5

Reactant 3

HCID 5742Guanidine HydrochlorideHCID 178470521HCID 178470521, compoundHCID 178512666HCID 178512666, compound

Product 1

HCID 178470523HCID 178470523, compoundYield 21.8%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
40 °C

Procedure

N-[(4-chloro-1-guanidino-7-isoquinolinyl)sulphonyl]cycloleucine trifluoroacetate ##STR48## NaH (1.12 g, 80% dispersion by wt in mineral oil, 37.3 mmol) was added portionwise to a stirred suspension of guanidine hydrochloride (5.85 g, 59.4 mmol) in DMSO (320 mL) and the mixture was heated at 30-50° C. under N2 for 30 min. N-[(1,4-Dichloro-1-guanidino-7-isoquinolinyl)sulphonyl]-cycloleucine ethyl ester (6.2 g, 14.9 mmol) was added in one portion and the mixture heated at 80° C. for 8 h. The cooled mixture concentrated in vacuo to ca. 160 mL and poured into water (800 mL). The aqueous mixture was extracted with EtOAc (4×150 mL) and the combined organic extracts were then washed with water, brine, dried (MgSO4) and evaporated in vacuo. The residue was purified by column chromatography upon silica gel using CH2Cl2 -MeOH-0.880NH3 (95:5:0.5 to 90:10:1) as eluant and then recrystallised from EtOAc to give N-[(4-chloro-1-guanidino-7-isoquinolinyl)sulphonyl]cyclo-leucine ethyl ester (1.43 g, 3.25 mmol) as a yellow solid.

Workup

  1. temperaturethe mixture heated at 80° C. for 8 h
  2. concentrationThe cooled mixture concentrated in vacuo to ca. 160 mL
  3. additionpoured into water (800 mL)
  4. extractionThe aqueous mixture was extracted with EtOAc (4×150 mL)
  5. washthe combined organic extracts were then washed with water, brine
  6. dry with materialdried (MgSO4)
  7. customevaporated in vacuo
  8. customThe residue was purified by column chromatography upon silica gel
  9. custom880NH3 (95:5:0.5 to 90:10:1) as eluant and then recrystallised from EtOAc

Sources & evidence

ORD record
ord-b9b535b45a5146a19cbb88aa710dc0b2
Source dataset
uspto-grants-2000_07
Patent number
US06093731

Reaction notes

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