Tris(dimethylamino)sulfonium difluorotrimethylsilicate → 4-(4-((R)-(4'-chlorobiphenyl-2-yl)((S)-1,1-dimethylethylsulfinamido)methyl)piperidin-1-yl)-N-(4-((R)-4-(ethyl(2-hydroxyethyl)amino)-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)phenylsulfonyl)benzamide

HRID 1476347ノート

反応式

HRID 1476347 の反応式
CN([S+](N(C)C)N(C)C)C.C[Si-](F)(F)(C)C.[Si]([O:34][CH2:35][CH2:36][N:37]([CH2:102][CH3:103])[CH2:38][CH2:39][C@@H:40]([NH:49][C:50]1[CH:55]=[CH:54][C:53]([S:56]([NH:59][C:60](=[O:94])[C:61]2[CH:66]=[CH:65][C:64]([N:67]3[CH2:72][CH2:71][CH:70]([C@H:73]([C:81]4[CH:86]=[CH:85][CH:84]=[CH:83][C:82]=4[C:87]4[CH:92]=[CH:91][C:90]([Cl:93])=[CH:89][CH:88]=4)[NH:74][S@:75]([C:77]([CH3:80])([CH3:79])[CH3:78])=[O:76])[CH2:69][CH2:68]3)=[CH:63][CH:62]=2)(=[O:58])=[O:57])=[CH:52][C:51]=1[S:95]([C:98]([F:101])([F:100])[F:99])(=[O:97])=[O:96])[CH2:41][S:42][C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1)(C(C)(C)C)(C1C=CC=CC=1)C1C=CC=CC=1>CN(C=O)C>[Cl:93][C:90]1[CH:91]=[CH:92][C:87]([C:82]2[CH:83]=[CH:84][CH:85]=[CH:86][C:81]=2[C@H:73]([NH:74][S@:75]([C:77]([CH3:78])([CH3:80])[CH3:79])=[O:76])[CH:70]2[CH2:71][CH2:72][N:67]([C:64]3[CH:65]=[CH:66][C:61]([C:60]([NH:59][S:56]([C:53]4[CH:54]=[CH:55][C:50]([NH:49][C@H:40]([CH2:39][CH2:38][N:37]([CH2:102][CH3:103])[CH2:36][CH2:35][OH:34])[CH2:41][S:42][C:43]5[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=5)=[C:51]([S:95]([C:98]([F:101])([F:100])[F:99])(=[O:96])=[O:97])[CH:52]=4)(=[O:58])=[O:57])=[O:94])=[CH:62][CH:63]=3)[CH2:68][CH2:69]2)=[CH:88][CH:89]=1

参加物

4

反応物 2

HCID 9795567Tris(dimethylamino)sulfonium difluorotrimethylsilicateHCID 86661889N-(4-((R)-4-((2-(tert-butyldiphenylsilyloxy)ethyl)(ethyl)amino)-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)phenylsulfonyl)-4-(4-((R)-(4'-chlorobiphenyl-2-yl)((S)-1,1-dimethylethylsulfinamido)methyl)piperidin-1-yl)benzamide

生成物 1

HCID 866618904-(4-((R)-(4'-chlorobiphenyl-2-yl)((S)-1,1-dimethylethylsulfinamido)methyl)piperidin-1-yl)-N-(4-((R)-4-(ethyl(2-hydroxyethyl)amino)-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)phenylsulfonyl)benzamide収率 114.6%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

A solution of TASF (0.46 ml. 0.46 mmol, 1 M in DMF) was added to a solution of N-(4-((R)-4-((2-(tert-butyldiphenylsilyloxy)ethyl)(ethyl)amino)-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)phenylsulfonyl)-4-(4-((R)-(4′-chlorobiphenyl-2-yl)((S)-1,1-dimethylethylsulfinamido)methyl)piperidin-1-yl)benzamide (EXAMPLE 12, STEP 1, 0.30 g, 0.23 mmol) in DMF (1.9 ml) and the reaction mixture was stirred at r.t for 1 hour. The reaction mixture was concentrated under reduced pressure, diluted with DCM and washed with H2O. The organic layer was dried (Na2SO4), concentrated under reduced pressure and dried under vacuum to give 4-(4-((R)-(4′-chlorobiphenyl-2-yl)((S)-1,1-dimethylethylsulfinamido)methyl)piperidin-1-yl)-N-(4-((R)-4-(ethyl(2-hydroxyethyl)amino)-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)phenylsulfonyl)benzamide (EXAMPLE 12, STEP 2, 0.28 g) which was used in the preparation of EXAMPLE 12, STEP 3, without further purification.

後処理

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. additiondiluted with DCM
  3. washwashed with H2O
  4. dry with materialThe organic layer was dried (Na2SO4)
  5. concentrationconcentrated under reduced pressure
  6. customdried under vacuum

出典と根拠

ORDレコード
ord-0f2e0da0a8de4f628929df6caface833
出典データセット
uspto-grants-2015_04
特許番号
US09018381B2

反応ノート

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