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

反応式

HRID 23840 の反応式
[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

参加物

7

反応物 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

生成物 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

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-86d0fc491dd246a7b4b9138f00311982
出典データセット
uspto-grants-2005_02
特許番号
US06852748B1

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