Water → HCID 178470337, compound

HRID 2289787Notes

Reaction equation

HRID 2289787 reaction equation
Cl.[Cl:2][C:3]1[C:12]2[C:7](=[CH:8][C:9]([S:13]([N:16]([CH3:25])[C:17]3([C:22]([OH:24])=[O:23])[CH2:21][CH2:20][CH2:19][CH2:18]3)(=[O:15])=[O:14])=[CH:10][CH:11]=2)[C:6]([NH:26][C:27]([NH2:29])=[NH:28])=[N:5][CH:4]=1.Cl.NC(N)=N.[CH2:35](OC(=O)C1(CCCC1)N(S(C1C=C2C(C(Cl)=CN=C2Cl)=CC=1)(=O)=O)C)[CH3:36].O>CS(C)=O>[CH2:35]([O:23][C:22](=[O:24])[C:17]1([CH2:21][CH2:20][CH2:19][CH2:18]1)[N:16]([S:13]([C:9]1[CH:8]=[C:7]2[C:12]([C:3]([Cl:2])=[CH:4][N:5]=[C:6]2[NH:26][C:27]([NH2:29])=[NH:28])=[CH:11][CH:10]=1)(=[O:14])=[O:15])[CH3:25])[CH3:36]

Participants

6

Reactant 4

HCID 962WaterHCID 5742Guanidine HydrochlorideHCID 16658247HCID 16658247, compoundHCID 178482301HCID 178482301, compound

Product 1

HCID 178470337HCID 178470337, compoundYield 54.8%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent2×

Conditions

Temperature
50 °C

Procedure

N-[(4-Chloro-1-guanidino-7-isoquinolinyl)sulphonyl]-N-(methyl)cycloleucine hydrochloride ##STR91## NaH (31 mg, 80% dispersion in mineral oil, 1.04 mmol) was added to a solution of guanidine hydrochloride (164 mg, 1.67 mmol) in DMSO (4 ml), and the solution heated at 50° C. for 1 h. N-[(1,4-Dichloro-7-isoquinolinyl)sulphonyl]-N-(methyl)cycloleucine ethyl ester (180 mg, 0.42 mmol) in DMSO (2 ml) was added, and the reaction heated at 80° C. for 3 h. The cooled reaction mixture was poured into water, and extracted with EtOAc. The combined organic extracts were washed with brine, dried (MgSO4), and evaporated in vacuo. The residual yellow oil was purified by column chromatography upon silica gel using CH2Cl2 -MeOH-0.880 NH3 (90:10:1) as eluant, and recrystallised from EtOAc to afford N-[(4-chloro-1-guanidino-7-isoquinolinyl)sulphonyl]-N-(methyl)cycloleucine ethyl ester (105 mg, 0.23 mmol) as a yellow solid.

Workup

  1. temperaturethe reaction heated at 80° C. for 3 h
  2. customThe cooled reaction mixture
  3. extractionextracted with EtOAc
  4. washThe combined organic extracts were washed with brine
  5. dry with materialdried (MgSO4)
  6. customevaporated in vacuo
  7. customThe residual yellow oil was purified by column chromatography upon silica gel
  8. custom880 NH3 (90:10:1) as eluant, and recrystallised from EtOAc

Sources & evidence

ORD record
ord-e15ba8ba24a24c27b1a00e716922c07a
Source dataset
uspto-grants-2000_07
Patent number
US06093731

Reaction notes

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