Triethylamine → (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 (2-hydroxy-ethyl)-amide

HRID 2374796Notes

Reaction equation

HRID 2374796 reaction equation
C(N(CC)CC)C.[C:8]([C:10]1[CH:50]=[CH:49][C:13]([CH2:14][C@@:15]2([CH3:48])[N:19]3[C:20]([S:23]([N:26]4[CH2:30][CH2:29][CH2:28][C@H:27]4[C:31]([NH:33][C@H:34](C)[C:35](O)=[O:36])=[O:32])(=[O:25])=[O:24])=[CH:21][N:22]=[C:18]3[N:17]([C:39]3[CH:44]=[C:43]([Cl:45])[CH:42]=[C:41]([Cl:46])[CH:40]=3)[C:16]2=[O:47])=[CH:12][CH:11]=1)#[N:9]>CN(C=O)C.CCOC(C)=O>[OH:36][CH2:35][CH2:34][NH:33][C:31]([C@@H:27]1[CH2:28][CH2:29][CH2:30][N:26]1[S:23]([C:20]1[N:19]2[C@@:15]([CH2:14][C:13]3[CH:12]=[CH:11][C:10]([C:8]#[N:9])=[CH:50][CH:49]=3)([CH3:48])[C:16](=[O:47])[N:17]([C:39]3[CH:40]=[C:41]([Cl:46])[CH:42]=[C:43]([Cl:45])[CH:44]=3)[C:18]2=[N:22][CH:21]=1)(=[O:24])=[O:25])=[O:32]

Participants

5

Reactant 2

HCID 8471TriethylamineHCID 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 acid

Product 1

HCID 10258289(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 (2-hydroxy-ethyl)-amideYield 104.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

The above amine HCl salt (0.93 g) was dissolved in anhydrous DMF (9 mL) by vigorously stirring at room temperature for 30 min. When all the amine salt was dissolved, triethylamine (1 mL) was added to the solution. (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) (1.18 g) in anhydrous DMF (1 mL) was then added to the reaction mixture and stirred at room temperature for 30 min. The reaction mixture was then diluted with EtOAc and washed with water (×2), 1N HCl, saturated NaHCO3 and brine. The organic phase was then dried over Na2SO4 and concentrated. The residue was purified by silica gel column chromatography using CH2Cl2 and MeOH (gradient 0-5% MeOH) as an eluent to afford 1.18 g of the title compound as a white foam (M+1, 617.2)

Workup

  1. stirringstirred at room temperature for 30 min
  2. washwashed with water (×2), 1N HCl, saturated NaHCO3 and brine
  3. dry with materialThe organic phase was then dried over Na2SO4
  4. concentrationconcentrated
  5. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-d59d96c9a6e643f59b67a78aaee838ad
Source dataset
uspto-grants-2008_12
Patent number
US07462637B2

Reaction notes

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