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 2374794노트

반응식

HRID 2374794 반응식
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]

참가 물질

6

반응물 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

생성물 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)-amide수율 71.7%

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-918fc06aad394db4b1c016b76c044c3b
출처 데이터셋
uspto-grants-2008_12
특허 번호
US07462637B2

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