Chlorotrimethylsilane → 3-((4-(2-((1-(4-Methoxy-2,6-dimethylphenylsulfonyl)pyrrolidin-2-yl)-methoxy)acetyl)piperazin-1-yl)methyl)benzonitrile hydrochloride

HRID 2090808

反応式

HRID 2090808 の反応式
COC1C=C(C)C(S(N2CCCC2COCC(O)=O)(=O)=O)=C(C)C=1.N1(CC2C=C(C=CC=2)C#N)CCNCC1.C(=O)([O-])O.[Na+].[CH3:45][O:46][C:47]1[CH:52]=[C:51]([CH3:53])[C:50]([S:54]([N:57]2[CH2:61][CH2:60][CH2:59][CH:58]2[CH2:62][O:63][CH2:64][C:65]([N:67]2[CH2:72][CH2:71][N:70]([CH2:73][C:74]3[CH:75]=[C:76]([CH:79]=[CH:80][CH:81]=3)[C:77]#[N:78])[CH2:69][CH2:68]2)=[O:66])(=[O:56])=[O:55])=[C:49]([CH3:82])[CH:48]=1.[Cl:83][Si](C)(C)C>ClCCl.CC(C)=O.C(OCC)C.C(OCC)C>[ClH:83].[CH3:45][O:46][C:47]1[CH:48]=[C:49]([CH3:82])[C:50]([S:54]([N:57]2[CH2:61][CH2:60][CH2:59][CH:58]2[CH2:62][O:63][CH2:64][C:65]([N:67]2[CH2:72][CH2:71][N:70]([CH2:73][C:74]3[CH:75]=[C:76]([CH:79]=[CH:80][CH:81]=3)[C:77]#[N:78])[CH2:69][CH2:68]2)=[O:66])(=[O:55])=[O:56])=[C:51]([CH3:53])[CH:52]=1

参加物

9

反応物 5

HCID 6397ChlorotrimethylsilaneHCID 516892Sodium BicarbonateHCID 27579481-(3-Cyanobenzyl)piperazineHCID 249454953-((4-(2-((1-(4-Methoxy-2,6-dimethylphenylsulfonyl)pyrrolidin-2-yl)methoxy)acetyl)piperazin-1-yl)methyl)benzonitrileHCID 59746454HCID 59746454、化合物

生成物 1

HCID 249454943-((4-(2-((1-(4-Methoxy-2,6-dimethylphenylsulfonyl)pyrrolidin-2-yl)-methoxy)acetyl)piperazin-1-yl)methyl)benzonitrile hydrochloride

試薬・触媒・溶媒 3

HCID 3283Diethyl Ether溶媒HCID 6344Dichloromethane溶媒2 回HCID 21584533Acetone diethylether溶媒

実験手順

N,N′-Carbonyldiimidazole (71 mg, 0.441 mmol) was added to a solution of 2-((1-(4-methoxy-2,6-dimethylphenylsulfonyl)pyrrolidin-2-yl)methoxy)acetic acid (150 mg, 0.420 mmol) in dichloromethane (7 ml), and the mixture was stirred for 1 h at room temperature. A solution of 3-(piperazin-1-ylmethyl)benzonitrile (84 mg, 0.420 mmol) in dichloromethane (3 ml) was then added, and the reaction mixture was stirred for 15 h at room temperature. Saturated sodium hydrogen carbonate solution (10 ml) was then added to the reaction mixture, and then the aqueous phase was extracted with dichloromethane (2×10 ml). The combined organic phases were extracted with saturated sodium chloride solution (10 ml), dried over sodium sulfate and concentrated in vacuo. The crude product was purified by flash chromatography using ethyl acetate/hexane/ammonia solution (25% aq.) (100:10:1). 3-((4-(2-((1-(4-methoxy-2,6-dimethylphenylsulfonyl)pyrrolidin-2-yl)methoxy)acetyl)piperazin-1-yl)methyl)benzonitrile (190 mg, 0.351 mmol) was dissolved in acetone/diethyl ether (1:1; 8 ml), and chlorotrimethylsilane (89 μl, 0.702 mmol) was added slowly. Diethyl ether (10 ml) was then added, and the mixture was stirred for 1 h at 0° C. The resulting precipitate was filtered off, dried with the exclusion of air and washed with diethyl ether.

後処理

  1. stirringthe reaction mixture was stirred for 15 h at room temperature
  2. extractionthe aqueous phase was extracted with dichloromethane (2×10 ml)
  3. extractionThe combined organic phases were extracted with saturated sodium chloride solution (10 ml)
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by flash chromatography
  7. stirringthe mixture was stirred for 1 h at 0° C
  8. filtrationThe resulting precipitate was filtered off
  9. customdried with the exclusion of air
  10. washwashed with diethyl ether

出典と根拠

ORDレコード
ord-f6d1b5778a6c4238a9d78d502876f1f9
出典データセット
uspto-grants-2013_05
特許番号
US08435978B2

関連ノート

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