Guanidine → HCID 178499193, compound

HRID 2289755Notes

Reaction equation

HRID 2289755 reaction equation
Cl.[Cl:2][C:3]1[C:12]2[C:7](=[CH:8][C:9]([S:13]([NH:16][C:17]3([C:23]([OH:25])=[O:24])[CH2:22][CH2:21][O: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.N[C:32](N)=N.ClC1C2C(=CC=C(S(NC3(C(OC)=O)CCOCC3)(=O)=O)C=2)C(Cl)=CN=1.NC(N)=N>CS(C)=O.O>[Cl:2][C:3]1[C:12]2[C:7](=[CH:8][C:9]([S:13]([NH:16][C:17]3([C:23]([O:25][CH3:32])=[O:24])[CH2:22][CH2:21][O: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

Participants

7

Reactant 4

HCID 3520GuanidineHCID 5742Guanidine HydrochlorideHCID 16658029HCID 16658029, compoundHCID 178479404HCID 178479404, compound

Product 1

HCID 178499193HCID 178499193, compoundYield 16.6%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolvent2×HCID 962WaterSolvent

Conditions

Temperature
50 °C

Procedure

4-{[(4-Chloro-1-guanidino-7-isoquinolinyl)sulphonyl]amino}tetrahydro-2H-pyran-4-carboxylic acid hydrochloride ##STR55## NaH (33.5 mg, 80% dispersion by wt in mineral oil, 1.12 mmol) was added in one portion to a stirred solution of guanidine hydrochloride (176 mg, 1.84 mmol) in DMSO (3.0 mL) under N2 and the mixture was heated at 50° C. for 15 min. Methyl 4-{[(1,4-dichloro-7-isoquinolinyl)sulphonyl]amino}tetrahydro-2H-pyran-4-carboxylate (187 mg, 0.446 mmol) was added in one portion and the mixture heated at 80° C. for 8 h. A second portion of guanidine (0.45 mmol) [prepared from guanidine hydrochloride and NaH] in DMSO (1.0 mL) was added and the mixture heated at 90° C. for an additional 4 h. The cooled mixture was poured into water (100 mL), extracted with EtOAc (3×50 mL) and the combined organic extracts were washed with brine, dried (Na2SO4). The solvents were evaporated in vacuo and the residue purified by column chromatography upon silica gel using CH2Cl2 -MeOH-0.880NH3 (95:5:0.5) as eluant, and then crystallised with EtOAc, to give to give methyl 4-{[(4-chloro-1-guanidino-7-isoquinolinyl)sulphonyl]amino}tetrahydro-2H-pyran-4-carboxylate (83 mg, 0.186 mmol) as a yellow solid.

Workup

  1. temperaturethe mixture heated at 80° C. for 8 h
  2. temperaturethe mixture heated at 90° C. for an additional 4 h
  3. extractionextracted with EtOAc (3×50 mL)
  4. washthe combined organic extracts were washed with brine
  5. dry with materialdried (Na2SO4)
  6. customThe solvents were evaporated in vacuo
  7. customthe residue purified by column chromatography upon silica gel
  8. custom880NH3 (95:5:0.5) as eluant, and then crystallised with EtOAc
  9. customto give

Sources & evidence

ORD record
ord-e415d9ec773d4cf8947795313a89b6c8
Source dataset
uspto-grants-2000_07
Patent number
US06093731

Reaction notes

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