(R)-2-({(S)-1-[(R)-5-(4-cyano-benzyl)-7-(3,5-dichloro-phenyl)-5-methyl-6-oxo-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-sulfonyl]-pyrrolidine-2-carbonyl}-amino)-propionic acid → (S)-1-[(R)-5-(4-Cyano-benzyl)-7-(3,5-dichloro-phenyl)-5-methyl-6-oxo-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-sulfonyl]-pyrrolidine-2-carboxylic acid amide

HRID 2374791Notes

Reaction equation

HRID 2374791 reaction equation
[C:1]([C:3]1[CH:43]=[CH:42][C:6]([CH2:7][C@@:8]2([CH3:41])[N:12]3[C:13]([S:16]([N:19]4[CH2:23][CH2:22][CH2:21][C@H:20]4[C:24]([NH:26][C@H](C)C(O)=O)=[O:25])(=[O:18])=[O:17])=[CH:14][N:15]=[C:11]3[N:10]([C:32]3[CH:37]=[C:36]([Cl:38])[CH:35]=[C:34]([Cl:39])[CH:33]=3)[C:9]2=[O:40])=[CH:5][CH:4]=1)#[N:2].Cl.N1CCC[C@H]1C(N)=O>C(Cl)Cl.CN(C)C1C=CN=CC=1>[C:1]([C:3]1[CH:43]=[CH:42][C:6]([CH2:7][C@@:8]2([CH3:41])[N:12]3[C:13]([S:16]([N:19]4[CH2:23][CH2:22][CH2:21][C@H:20]4[C:24]([NH2:26])=[O:25])(=[O:18])=[O:17])=[CH:14][N:15]=[C:11]3[N:10]([C:32]3[CH:33]=[C:34]([Cl:39])[CH:35]=[C:36]([Cl:38])[CH:37]=3)[C:9]2=[O:40])=[CH:5][CH:4]=1)#[N:2]

Participants

5

Reactant 2

HCID 12136436(R)-2-({(S)-1-[(R)-5-(4-cyano-benzyl)-7-(3,5-dichloro-phenyl)-5-methyl-6-oxo-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-sulfonyl]-pyrrolidine-2-carbonyl}-amino)-propionic acidHCID 12707183(S)-Pyrrolidine-2-carboxamide monohydrochloride

Product 1

HCID 12136443(S)-1-[(R)-5-(4-Cyano-benzyl)-7-(3,5-dichloro-phenyl)-5-methyl-6-oxo-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-sulfonyl]-pyrrolidine-2-carboxylic acid amideYield 245.9%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of (R)-5-(4-cyano-benzyl)-7-(3,5-dichloro-phenyl)-5-methyl-6-oxo-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-sulfonyl chloride (see Example 5) (50 mg, 0.10 mmol) in anhydrous methylene chloride (1 mL) was added 4-dimethylaminopyridine (DMAP) (37 mg, 0.30 mmol). L-Proline amide hydrochloride (69 mg, 0.30 mmol) was added to the mixture and the reaction was stirred for 18 h at room temperature under nitrogen. The reaction was concentrated and the residue was purified by column chromatography over silica gel (gradient elution with 35-50% EtOAc in hexanes) to provide 141 mg of (S)-1-[(R)-5-(4-Cyano-benzyl)-7-(3,5-dichloro-phenyl)-5-methyl-6-oxo-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-sulfonyl]-pyrrolidine-2-carboxylic acid amide as a white solid.

Workup

  1. concentrationThe reaction was concentrated
  2. customthe residue was purified by column chromatography over silica gel (gradient elution with 35-50% EtOAc in hexanes)

Sources & evidence

ORD record
ord-de445e5608364d7f912728d6f6f94773
Source dataset
uspto-grants-2008_12
Patent number
US07462637B2

Reaction notes

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