Hydrochloric Acid → (S)-1-[(R)-7-(3,5-dichloro-phenyl)-5-methyl-6-oxo-5-(4-pyrimidin-5-yl-benzyl)-6,7-dihydro-5H-imidazo[1,2-alpha]imidazole-3-sulfonyl]-pyrrolidine-2-carboxylic acid (2-carbamoyl-ethyl)-amide

HRID 2374800

反応式

HRID 2374800 の反応式
C[N:2](C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C(O[C:28]([C@@H:30]1[CH2:34][CH2:33][CH2:32][N:31]1[S:35]([C:38]1[N:42]2[C@:43]([CH3:68])([CH2:55][C:56]3[CH:61]=[CH:60][C:59]([C:62]4[CH:63]=[N:64][CH:65]=[N:66][CH:67]=4)=[CH:58][CH:57]=3)[C:44](=[O:54])[N:45]([C:46]3[CH:51]=[C:50]([Cl:52])[CH:49]=[C:48]([Cl:53])[CH:47]=3)[C:41]2=[N:40][CH:39]=1)(=[O:37])=[O:36])=[O:29])(C)(C)C.C[O:70][C:71](=O)[CH2:72][CH2:73][NH2:74].CCN(C(C)C)C(C)C.Cl>CN(C=O)C.C(Cl)Cl.C(Cl)Cl>[C:71]([CH2:72][CH2:73][NH:74][C:28]([C@@H:30]1[CH2:34][CH2:33][CH2:32][N:31]1[S:35]([C:38]1[N:42]2[C@:43]([CH3:68])([CH2:55][C:56]3[CH:57]=[CH:58][C:59]([C:62]4[CH:63]=[N:64][CH:65]=[N:66][CH:67]=4)=[CH:60][CH:61]=3)[C:44](=[O:54])[N:45]([C:46]3[CH:51]=[C:50]([Cl:52])[CH:49]=[C:48]([Cl:53])[CH:47]=3)[C:41]2=[N:40][CH:39]=1)(=[O:37])=[O:36])=[O:29])(=[O:70])[NH2:2]

参加物

8

反応物 5

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 192794Methyl beta-alanateHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 12136449(S)-1-[(R)-7-(3,5-dichloro-phenyl)-5-methyl-6-oxo-5-(4-pyrimidin-5-yl-benzyl)-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-sulfonyl]-pyrrolidine-2-carboxylic acid tert-butyl ester

生成物 1

HCID 59985285(S)-1-[(R)-7-(3,5-dichloro-phenyl)-5-methyl-6-oxo-5-(4-pyrimidin-5-yl-benzyl)-6,7-dihydro-5H-imidazo[1,2-alpha]imidazole-3-sulfonyl]-pyrrolidine-2-carboxylic acid (2-carbamoyl-ethyl)-amide収率 10.3%

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒HCID 22350042dichloromethane N,N-dimethylformamide溶媒

反応条件

温度
50 °C

実験手順

TBTU (0.15 g), (S)-1-[(R)-7-(3,5-dichloro-phenyl)-5-methyl-6-oxo-5-(4-pyrimidin-5-yl-benzyl)-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-sulfonyl]-pyrrolidine-2-carboxylic acid (Example 14) (0.20 g), β-alanine methyl ester (0.067 g) and DIPEA (0.14 mL) were combined in 1% DMF-CH2Cl2 (10.1 mL) at room temperature and the solution was stirred for 1 h. The reaction was diluted with CH2Cl2, poured into 1N HCl, and extracted with CH2Cl2. The organic layers were combined and washed with saturated aqueous NaHCO3 followed by H2O. The combined organic phase was dried (Na2SO4), filtered and concentrated. The resultant residue was re-dissolved in 2N NH3—CH3OH (10 mL) and heated to 40-60° C. for 48 h. The volatiles were removed and the residue was purified by silica gel chromatography to afford the title compound (0.021 g) as a foam (697.2, M+1).

後処理

  1. extractionextracted with CH2Cl2
  2. washwashed with saturated aqueous NaHCO3
  3. dry with materialThe combined organic phase was dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. dissolutionThe resultant residue was re-dissolved in 2N NH3—CH3OH (10 mL)
  7. customThe volatiles were removed
  8. customthe residue was purified by silica gel chromatography

出典と根拠

ORDレコード
ord-81a9cca2c9aa4e63b023c50ef4907782
出典データセット
uspto-grants-2008_12
特許番号
US07462637B2

関連ノート

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