Oxalyl chloride → HCID 178483839, compound

HRID 2289790Notes

Reaction equation

HRID 2289790 reaction equation
[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([S:12]([N:15]3[CH2:19][CH2:18][CH2:17][C@@H:16]3[C:20]([NH:22][CH2:23][CH2:24][N:25]([CH3:27])[CH3:26])=[O:21])(=[O:14])=[O:13])=[CH:9][CH:10]=2)[C:5]([NH:28][C:29]([NH2:31])=[NH:30])=[N:4][CH:3]=1.C(Cl)(=O)C(Cl)=O.NCCN(C)C>CN(C=O)C.C(Cl)Cl>[NH3:4].[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([S:12]([N:15]3[CH2:19][CH2:18][CH2:17][C@@H:16]3[C:20]([NH:22][CH2:23][CH2:24][N:25]([CH3:27])[CH3:26])=[O:21])(=[O:13])=[O:14])=[CH:9][CH:10]=2)[C:5]([NH:28][C:29]([NH2:31])=[NH:30])=[N:4][CH:3]=1

Participants

7

Reactant 3

HCID 65578Oxalyl chlorideHCID 66053N,N-DimethylethylenediamineHCID 178483839HCID 178483839, compound

Product 2

HCID 222AmmoniaHCID 178483839HCID 178483839, compoundYield 131%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent

Procedure

(2R)-1-({4-Chloro-1-guanidino-7-isoquinolinyl}sulphonyl)-N-[2-(dimethylamino)ethyl]-2-pyrrolidinecarboxamide ##STR93## N-[(4-Chloro-1-guanidino-7-isoquinolinyl)sulphonyl]-L-proline hydrochloride (300 mg, 0.69 -mmol) was suspended in a solution of DMF (5 drops) and CH2Cl2 (15 ml), and oxalyl chloride (150 μl, 1.72 mmol) added dropwise. The reaction was stirred at room temperature for 3 h, then concentrated in vacuo and azeotroped with toluene. The residue was dissolved in CH2Cl2 (15 ml), N-(2-aminoethyl)-N,N-dimethylamine (1 ml, 0.9 mmol) added and the reaction stirred at room temperature for 2 h. The mixture was evaporated in vacuo, the residue partitioned between EtOAc and Na2CO3 solution, the layers separated, and the organic phase washed with brine, dried (Na2SO4) and evaporated in vacuo. The residual yellow solid was purified by column chromatography upon silica gel using an elution gradient of CH2Cl2 -MeOH-0.880 NH3 (95:5:0.5 to 90:10:1) to give (2R)-1-({4-chloro-1-guanidino-7-isoquinolinyl}sulphonyl)-N-[2-(dimethylamino)ethyl]-2-pyrrolidinecarboxamide (195 mg, 0.42 mmol) as a yellow solid.

Workup

  1. additionadded dropwise
  2. concentrationconcentrated in vacuo
  3. customazeotroped with toluene
  4. dissolutionThe residue was dissolved in CH2Cl2 (15 ml)
  5. stirringthe reaction stirred at room temperature for 2 h
  6. customThe mixture was evaporated in vacuo
  7. customthe residue partitioned between EtOAc and Na2CO3 solution
  8. customthe layers separated
  9. washthe organic phase washed with brine
  10. dry with materialdried (Na2SO4)
  11. customevaporated in vacuo
  12. customThe residual yellow solid was purified by column chromatography upon silica gel using an elution gradient of CH2Cl2 -MeOH-0

Sources & evidence

ORD record
ord-48766e3c3cef47d798bfbac81b431e40
Source dataset
uspto-grants-2000_07
Patent number
US06093731

Reaction notes

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