Dimethylformamide → (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-2-methyl-propyl)-amide

HRID 2374794Notes

Reaction equation

HRID 2374794 reaction equation
Cl.[OH:2][C:3]([CH3:14])([CH3:13])[CH2:4][NH:5][C:6]([CH:8]1[CH2:12][CH2:11][CH2:10][NH:9]1)=[O:7].C(N(CC)CC)C.[C:22]([C:24]1[CH:64]=[CH:63][C:27]([CH2:28][C@@:29]2([CH3:62])[N:33]3[C:34]([S:37](N4CCC[C@H]4C(N[C@H](C)C(O)=O)=O)(=[O:39])=[O:38])=[CH:35][N:36]=[C:32]3[N:31]([C:53]3[CH:58]=[C:57]([Cl:59])[CH:56]=[C:55]([Cl:60])[CH:54]=3)[C:30]2=[O:61])=[CH:26][CH:25]=1)#[N:23].CN(C=O)C>C(Cl)Cl>[OH:2][C:3]([CH3:14])([CH3:13])[CH2:4][NH:5][C:6]([C@@H:8]1[CH2:12][CH2:11][CH2:10][N:9]1[S:37]([C:34]1[N:33]2[C@@:29]([CH2:28][C:27]3[CH:63]=[CH:64][C:24]([C:22]#[N:23])=[CH:25][CH:26]=3)([CH3:62])[C:30](=[O:61])[N:31]([C:53]3[CH:54]=[C:55]([Cl:60])[CH:56]=[C:57]([Cl:59])[CH:58]=3)[C:32]2=[N:36][CH:35]=1)(=[O:38])=[O:39])=[O:7]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 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 acidHCID 86597006Pyrrolidine-2-carboxylic acid (2-hydroxy-2-methyl-propyl)-amide hydrochloride

Product 1

HCID 10258647(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-2-methyl-propyl)-amideYield 71.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Pyrrolidine-2-carboxylic acid (2-hydroxy-2-methyl-propyl)-amide hydrochloride (0.241 g, 1.082 mmol) was dissolved in CH2Cl2 and triethylamine (0.206 mL, 1.513 mmol) was added to the solution. The reaction mixture was stirred at room temperature for 10 min. (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) (0.3 g, 0.605 mmol) in CH2Cl2 was added to the reaction mixture and stirred for 1 h. DMF (0.5 mL) was then added to the reaction mixture and stirred for another 30 min. The reaction solution was washed with 1N HCl and saturated NaHCO3. The organic phase was dried over Na2SO4 and concentrated. The crude product was purified by silica gel preparative thin layer chromatography using CH2Cl2-MeOH (10:1) as an eluent to afford 0.28 g of the title compound (M+1, 644.98).

Workup

  1. additionwas added to the reaction mixture
  2. stirringstirred for another 30 min
  3. washThe reaction solution was washed with 1N HCl and saturated NaHCO3
  4. dry with materialThe organic phase was dried over Na2SO4
  5. concentrationconcentrated
  6. customThe crude product was purified by silica gel preparative thin layer chromatography

Sources & evidence

ORD record
ord-918fc06aad394db4b1c016b76c044c3b
Source dataset
uspto-grants-2008_12
Patent number
US07462637B2

Reaction notes

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