HCID 178418361, compound → HCID 178511943, compound

HRID 1961499Notes

Reaction equation

HRID 1961499 reaction equation
[C:1]([C:4]1[CH:56]=[CH:55][C:7]2[NH:8][C:9]([C:11]3[CH:12]=[C:13]([CH2:29][C:30]([NH:32][C@@H:33]([CH2:44][C:45]([O:47]CC4C=CC=CC=4)=[O:46])[C:34]([O:36]CC4C=CC=CC=4)=[O:35])=[O:31])[CH:14]=[C:15]([C:18]4[CH:23]=[C:22]([S:24](=[O:27])(=[O:26])[NH2:25])[CH:21]=[CH:20][C:19]=4[OH:28])[C:16]=3[OH:17])=[N:10][C:6]=2[CH:5]=1)(=[NH:3])[NH2:2].[H][H]>C(O)(=O)C.O.[OH-].[OH-].[Pd+2].[Pd]>[C:1]([C:4]1[CH:56]=[CH:55][C:7]2[NH:8][C:9]([C:11]3[CH:12]=[C:13]([CH2:29][C:30]([NH:32][C@@H:33]([CH2:44][C:45]([OH:47])=[O:46])[C:34]([OH:36])=[O:35])=[O:31])[CH:14]=[C:15]([C:18]4[CH:23]=[C:22]([S:24](=[O:27])(=[O:26])[NH2:25])[CH:21]=[CH:20][C:19]=4[OH:28])[C:16]=3[OH:17])=[N:10][C:6]=2[CH:5]=1)(=[NH:2])[NH2:3]

Participants

7

Reactant 2

HCID 178418361HCID 178418361, compoundHCID 178511942dibenzyl (S)-2-{2-[5-(5-carbamimidoyl-1H-benzimidazol-2-yl)-6,2'-dihydroxy-5'-sulfamoylbiphenyl-3-yl]acetylamino}succinate

Product 1

HCID 178511943HCID 178511943, compoundYield 52.1%

Reagents, catalysts & solvents 4

HCID 23938PalladiumCatalystHCID 9942167Palladium hydroxideCatalyst2×HCID 176Acetic AcidSolventHCID 962WaterSolvent2×

Procedure

Crude dibenzyl(S)-2-{2-[5-(5-carbamimidoyl-1H-benzimidazol-2-yl)-6,2′-dihydroxy-5′-sulfamoylbiphenyl-3-yl]acetylamino}succinate (18 g) was dissolved in a 1:1 mixture of acetic acid and water (800 mL), assisted by sonication. To this solution was added palladium hydroxide on carbon (Pearlman's catalyst, 20 wt % Pd on a dry weight basis, containing 50% water by weight; 7.0 g). The reaction mixture was pressurized to 30 psi with hydrogen and the suspension was shaken on a Parr apparatus for 10 h. The catalyst was removed by filtration and the solvent was removed in vacuo. Crude (S)-2-{2-[5-(5-carbamimidoyl-1H-benzimidazol-2-yl)-6,2′-dihydroxy-5′-sulfamoylbiphenyl-3-yl]acetylamino}succinic acid was purified by preparative reverse-phase HPLC to give (S)-2-{2-[5-(5-carbamimidoyl-1H-benzimidazol-2-yl)-6,2′-dihydroxy-5′-sulfamoylbiphenyl-3-yl]acetylamino}succinic acid (7.2 g).

Workup

  1. customassisted by sonication
  2. customThe catalyst was removed by filtration
  3. customthe solvent was removed in vacuo
  4. customCrude (S)-2-{2-[5-(5-carbamimidoyl-1H-benzimidazol-2-yl)-6,2′-dihydroxy-5′-sulfamoylbiphenyl-3-yl]acetylamino}succinic acid was purified by preparative reverse-phase HPLC

Sources & evidence

ORD record
ord-cb1c5385025241f68774d49ad7df99a1
Source dataset
uspto-grants-2013_04
Patent number
US08415328B2

Reaction notes

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