(S)-2-[(S)-4-benzyloxycarbonyl-2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-butyryl]-3-phenethylcarbamoyl-tetrahydro-pyridazine-1-carboxylic acid benzyl ester → (S)-4-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-5-oxo-5-((S)-6-phenethylcarbamoyl-tetrahydro-pyridazin-1-yl)-pentanoic acid

HRID 1668415Notes

Reaction equation

HRID 1668415 reaction equation
C(OC([N:11]1[CH2:16][CH2:15][CH2:14][C@@H:13]([C:17](=[O:27])[NH:18][CH2:19][CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[N:12]1[C:28](=[O:53])[C@@H:29]([N:42]1[C:50](=[O:51])[C:49]2[C:44](=[CH:45][CH:46]=[CH:47][CH:48]=2)[C:43]1=[O:52])[CH2:30][CH2:31][C:32]([O:34]CC1C=CC=CC=1)=[O:33])=O)C1C=CC=CC=1>CO.[Pd]>[O:51]=[C:50]1[C:49]2[C:44](=[CH:45][CH:46]=[CH:47][CH:48]=2)[C:43](=[O:52])[N:42]1[C@H:29]([C:28](=[O:53])[N:12]1[C@H:13]([C:17](=[O:27])[NH:18][CH2:19][CH2:20][C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)[CH2:14][CH2:15][CH2:16][NH:11]1)[CH2:30][CH2:31][C:32]([OH:34])=[O:33]

Participants

4

Reactant 1

HCID 57612765(S)-2-[(S)-4-benzyloxycarbonyl-2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-butyryl]-3-phenethylcarbamoyl-tetrahydro-pyridazine-1-carboxylic acid benzyl ester

Product 1

HCID 57612783(S)-4-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-5-oxo-5-((S)-6-phenethylcarbamoyl-tetrahydro-pyridazin-1-yl)-pentanoic acidYield 95.3%

Reagents, catalysts & solvents 2

HCID 887MethanolCatalystHCID 23938PalladiumCatalyst

Procedure

A solution/suspension of (S)-2-[(S)-4-benzyloxycarbonyl-2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-butyryl]-3-phenethylcarbamoyl-tetrahydro-pyridazine-1-carboxylic acid benzyl ester (1.13 g) and Pd/C (350 mg, 10% on carbon) in MeOH (15 mL, with 2 drops of acetic acid) in a 1,000 mL round flask is vigorously stirred at room temperature, under hydrogen gas (at atmosphere pressure) from a balloon for 3 hours. After degassed by house vacuum for 10 minutes, the reaction mixture is filtered to remove catalyst and concentrated. The crude product is diluted with CH2Cl2/H2O (10 mL, 8/2) and neutralized with 10% NH4OH to Ph=7. After dried and concentrated, the crude product is purified by chromatography (CH2Cl2/MeOH:97/3) to give (S)-4-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-5-oxo-5-((S)-6-phenethylcarbamoyl-tetrahydro-pyridazin-1-yl)-pentanoic acid (0.74 g, 95.3%) as pale solid. (NMR and MS data confirmed, U-3133-63).

Workup

  1. customAfter degassed by house vacuum for 10 minutes
  2. filtrationthe reaction mixture is filtered
  3. customto remove catalyst
  4. concentrationconcentrated
  5. additionThe crude product is diluted with CH2Cl2/H2O (10 mL, 8/2)
  6. customAfter dried
  7. concentrationconcentrated
  8. customthe crude product is purified by chromatography (CH2Cl2/MeOH:97/3)

Sources & evidence

ORD record
ord-616cf379e19941b889447869fe6aa467
Source dataset
uspto-grants-2011_08
Patent number
US07989441B2

Reaction notes

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