Water → HCID 178512653, compound

HRID 2289775Notes

Reaction equation

HRID 2289775 reaction equation
FC(F)(F)C(O)=O.[Cl:8][C:9]1[C:18]2[C:13](=[CH:14][C:15]([C:19]([NH:21][CH:22]([C:27]([OH:29])=[O:28])[CH2:23][C:24]([OH:26])=[O:25])=[O:20])=[CH:16][CH:17]=2)[C:12]([NH:30][C:31]([NH2:33])=[NH:32])=[N:11][CH:10]=1.Cl.NC(N)=N.ClC1C2C(=CC=C(C(NC(C(O)=O)CC(O)=O)=O)C=2)C(Cl)=CN=1.O>CS(C)=O>[Cl:8][C:9]1[C:18]2[C:13](=[CH:14][C:15]([C:19]([NH:21][CH:22]([C:27]([OH:29])=[O:28])[CH2:23][C:24]([OH:26])=[O:25])=[O:20])=[CH:16][CH:17]=2)[C:12]([NH:30][C:31]([NH2:33])=[NH:32])=[N:11][CH:10]=1

Participants

6

Reactant 4

HCID 962WaterHCID 5742Guanidine HydrochlorideHCID 18698241HCID 18698241, compoundHCID 178512654HCID 178512654, compound

Product 1

HCID 178512653HCID 178512653, compound

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
50 °C

Procedure

N-[(4-Chloro-1-guanidino-7-isoquinolinyl)carbonyl]-DL-aspartic acid trifluoroacetate ##STR71## NaH (53 mg, 80% dispersion in mineral oil, 1.77 mmol) was added to a solution of guanidine hydrochloride (168 mg, 1.76 mmol) in DMSO (6 mL) and the solution ws heated to 50° C. for 30 min. N-[(1,4-Dichloro-7-isoquinolinyl)carbonyl]-DL-aspartic acid a,,-di-t-butyl ester (330 mg, 0.70 mmol) was added and the mixture heated at 80-90° C. overnight. The cooled mixture was poured into water (50 mL) and extracted with EtOAc extract (5×20 mL). The combined organic extracts were washed with water, brine, dried (Na2SO4) and evaporated in vacuo. The residue was purified by (i), trituration with i-Pr2O (ii), column chromatography on silica gel using CH2Cl2 -MeOH-0.880NH3 (95:5:0.5) as eluant, and (iii), crystallisation from i-Pr2O, to give N-[(4-chloro-1-guanidino-7-isoquinolinyl)carbonyl]-DL-aspartic acid at,-di-t-butyl ester (145 mg, 0.29 mmol) as a yellow solid.

Workup

  1. temperaturethe mixture heated at 80-90° C. overnight
  2. extractionextracted with EtOAc
  3. extractionextract (5×20 mL)
  4. washThe combined organic extracts were washed with water, brine
  5. dry with materialdried (Na2SO4)
  6. customevaporated in vacuo
  7. customThe residue was purified by (i), trituration with i-Pr2O (ii), column chromatography on silica gel
  8. custom880NH3 (95:5:0.5) as eluant, and (iii), crystallisation from i-Pr2O

Sources & evidence

ORD record
ord-36278975d3bc4661a6e0d0697de5f0da
Source dataset
uspto-grants-2000_07
Patent number
US06093731

Reaction notes

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