Trifluoroacetic acid → (S)-1-[(R)5-(4-cyano-benzyl)-7-(3,5-dichloro-phenyl)-5-methyl-6-oxo-6,7-dihydro-5H-imidazo[1,2-alpha]imidazole-3-sulfonyl]-pyrrolidine-2-carboxylic acid ((R)-5-oxo-tetrahydro-furan-2-ylmethyl)amide

HRID 23840

반응식

HRID 23840 반응식
[C:1]([C:3]1[CH:38]=[CH:37][C:6]([CH2:7][C@@:8]2([CH3:36])[N:12]3[C:13]([S:16]([N:19]4[CH2:23][CH2:22][CH2:21][C@H:20]4[C:24](O)=[O:25])(=[O:18])=[O:17])=[CH:14][N:15]=[C:11]3[N:10]([C:27]3[CH:32]=[C:31]([Cl:33])[CH:30]=[C:29]([Cl:34])[CH:28]=3)[C:9]2=[O:35])=[CH:5][CH:4]=1)#[N:2].CN(C(O[N:47]1N=N[C:49]2[CH:50]=CC=C[C:48]1=2)=[N+](C)C)C.[B-](F)(F)(F)F.CCN(C(C)C)C(C)C.F[C:71](F)(F)[C:72]([OH:74])=[O:73]>CN(C=O)C.CCOC(C)=O>[O:73]=[C:72]1[O:74][C@@H:49]([CH2:48][NH:47][C:24]([C@@H:20]2[CH2:21][CH2:22][CH2:23][N:19]2[S:16]([C:13]2[N:12]3[C@@:8]([CH2:7][C:6]4[CH:5]=[CH:4][C:3]([C:1]#[N:2])=[CH:38][CH:37]=4)([CH3:36])[C:9](=[O:35])[N:10]([C:27]4[CH:32]=[C:31]([Cl:33])[CH:30]=[C:29]([Cl:34])[CH:28]=4)[C:11]3=[N:15][CH:14]=2)(=[O:18])=[O:17])=[O:25])[CH2:50][CH2:71]1

참가 물질

7

반응물 4

HCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 12136447(S)-1-[(R)-5-(4-cyano-benzyl)-7-(3,5-dichloro-phenyl)-5-methyl-6-oxo-6,7-dihydro-5H-imidazo[1,2-alpha]imidazole-3-sulfonyl]-pyrrolidine-2-carboxylic acid

생성물 1

HCID 12136445(S)-1-[(R)5-(4-cyano-benzyl)-7-(3,5-dichloro-phenyl)-5-methyl-6-oxo-6,7-dihydro-5H-imidazo[1,2-alpha]imidazole-3-sulfonyl]-pyrrolidine-2-carboxylic acid ((R)-5-oxo-tetrahydro-furan-2-ylmethyl)amide

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

To a solution of (S)-1-[(R)-5-(4-cyano-benzyl)-7-(3,5-dichloro-phenyl)-5-methyl-6-oxo-6,7-dihydro-5H-imidazo[1,2-α]imidazole-3-sulfonyl]-pyrrolidine-2-carboxylic acid (see Example 5) (0.1 g, 0.174 mmol) in anhydrous DMF was added the above mixture of amines (0.030 g), followed by TBTU (0.084 g, 0.261 mmol) followed by DIPEA (0.075 mL, 0.435 mmol). The reaction mixture was stirred at room temperature for 30 min. The reaction mixture was then diluted with EtOAc and washed with water (x3), 1N HCl, and saturated NaHCO3. The organic phase was dried over Na2SO4 and concentrated. The resulting residue was dissolved in CH2Cl2 and trifluoroacetic acid (1 eq) was added to the solution. The reaction mixture was stirred at room temperature for 3 h and washed with saturated NaHCO3 and water. The organic phase was dried over Na2SO4 and concentrated. The resulting residue was purified by silica gel preparative thin layer chromatography using CH2Cl2—MeOH (95:5) as an eluent to afford 0.063 g of the title compound as a white foam (M+1,671.1).

후처리

  1. washwashed with water (x3), 1N HCl, and saturated NaHCO3
  2. dry with materialThe organic phase was dried over Na2SO4
  3. concentrationconcentrated
  4. dissolutionThe resulting residue was dissolved in CH2Cl2
  5. stirringThe reaction mixture was stirred at room temperature for 3 h
  6. washwashed with saturated NaHCO3 and water
  7. dry with materialThe organic phase was dried over Na2SO4
  8. concentrationconcentrated
  9. customThe resulting residue was purified by silica gel preparative thin layer chromatography

출처 및 근거

ORD 기록
ord-86d0fc491dd246a7b4b9138f00311982
출처 데이터셋
uspto-grants-2005_02
특허 번호
US06852748B1

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