Sodium hydride → HCID 178472460, compound

HRID 2289760Notes

Reaction equation

HRID 2289760 reaction equation
Cl.[Cl:2][C:3]1[C:12]2[C:7](=[CH:8][C:9]([S:13]([NH:16][C@H:17]3[CH2:22][CH2:21][C@H:20]([C:23]([OH:25])=[O:24])[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.[H-].[Na+].Cl[C:33]1[C:42]2C(=CC=C(S(N[C@H]3CC[C@H](C(OCC)=O)CC3)(=O)=O)C=2)C(Cl)=CN=1>COCCOC.CC(N(C)C)=O>[Cl:2][C:3]1[C:12]2[C:7](=[CH:8][C:9]([S:13]([NH:16][C@H:17]3[CH2:22][CH2:21][C@H:20]([C:23]([O:25][CH2:33][CH3:42])=[O:24])[CH2:19][CH2:18]3)(=[O:14])=[O:15])=[CH:10][CH:11]=2)[C:6]([NH:26][C:27]([NH2:29])=[NH:28])=[N:5][CH:4]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 178472459HCID 178472459, compoundHCID 178479410HCID 178479410, compound

Product 1

HCID 178472460HCID 178472460, compoundYield 19.2%

Reagents, catalysts & solvents 2

HCID 80711,2-DimethoxyethaneSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
60 °C

Procedure

trans-4-{[(4-Chloro-1-guanidino-7-isoquinolinyl)sulphonyl]amino}cyclohexanecarboxylic acid hydrochloride ##STR59## Guanidine hydrochloride (273 mg, 2.86 mmol) was added in one portion to a stirred suspension of NaH (55 mg, 80% dispersion by wt in mineral oil, 1.82 mmol) in DME (10 mL) and the mixture was heated at 60° C. under N2 for 30 min. A solution of ethyl trans-4-{[(1,4-dichloro-7-isoquinolinyl)sulphonyl]amino}cyclohexanecarboxylate (370 mg, 0.78 mmol) in DMA (10 mL) was added and the mixture heated at 90° C. for 3 h. The solvents were evaporated in vacuo, the residue was partitioned between Et2O (100 mL), aqueous NH4Cl (10 mL), and water (150 mL). The separated aqueous phase was extracted with Et2O (3×100 mL) and the combined organic extracts were dried (MgSO4) and evaporated in vacuo. The residue was purified by column chromatography upon silica gel using toluene-i-PrOH-0.880NH3 (100:0:0 to 90:10:0.05) as eluant to give ethyl trans-4-{[(4-chloro-1-guanidino-7-isoquinolinyl)sulphonyl]amino}cyclohexanecarboxylate (70 mg, 0.15 mmol).

Workup

  1. temperaturethe mixture heated at 90° C. for 3 h
  2. customThe solvents were evaporated in vacuo
  3. customthe residue was partitioned between Et2O (100 mL), aqueous NH4Cl (10 mL), and water (150 mL)
  4. extractionThe separated aqueous phase was extracted with Et2O (3×100 mL)
  5. dry with materialthe combined organic extracts were dried (MgSO4)
  6. customevaporated in vacuo
  7. customThe residue was purified by column chromatography upon silica gel

Sources & evidence

ORD record
ord-971618ff93c4470ab4603f9c9ac963f5
Source dataset
uspto-grants-2000_07
Patent number
US06093731

Reaction notes

Loading…