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

HRID 1476349ノート

反応式

HRID 1476349 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]1[CH2:42][CH2:41][N:40]([CH2:43][CH2:44][C@@H:45]([NH:54][C:55]2[CH:60]=[CH:59][C:58]([S:61]([NH:64][C:65](=[O:99])[C:66]3[CH:71]=[CH:70][C:69]([N:72]4[CH2:77][CH2:76][CH:75]([C@H:78]([C:86]5[CH:91]=[CH:90][CH:89]=[CH:88][C:87]=5[C:92]5[CH:97]=[CH:96][C:95]([Cl:98])=[CH:94][CH:93]=5)[NH:79][S@:80]([C:82]([CH3:85])([CH3:84])[CH3:83])=[O:81])[CH2:74][CH2:73]4)=[CH:68][CH:67]=3)(=[O:63])=[O:62])=[CH:57][C:56]=2[S:100]([C:103]([F:106])([F:105])[F:104])(=[O:102])=[O:101])[CH2:46][S:47][C:48]2[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=2)[CH2:39][CH2:38]1)(C(C)(C)C)(C1C=CC=CC=1)C1C=CC=CC=1>CN(C=O)C>[Cl:98][C:95]1[CH:94]=[CH:93][C:92]([C:87]2[CH:88]=[CH:89][CH:90]=[CH:91][C:86]=2[C@H:78]([NH:79][S@:80]([C:82]([CH3:85])([CH3:84])[CH3:83])=[O:81])[CH:75]2[CH2:74][CH2:73][N:72]([C:69]3[CH:68]=[CH:67][C:66]([C:65]([NH:64][S:61]([C:58]4[CH:59]=[CH:60][C:55]([NH:54][C@H:45]([CH2:44][CH2:43][N:40]5[CH2:39][CH2:38][N:37]([CH2:36][CH2:35][OH:34])[CH2:42][CH2:41]5)[CH2:46][S:47][C:48]5[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=5)=[C:56]([S:100]([C:103]([F:106])([F:105])[F:104])(=[O:101])=[O:102])[CH:57]=4)(=[O:63])=[O:62])=[O:99])=[CH:71][CH:70]=3)[CH2:77][CH2:76]2)=[CH:97][CH:96]=1

参加物

4

反応物 2

HCID 9795567Tris(dimethylamino)sulfonium difluorotrimethylsilicateHCID 86661892N-(4-((R)-4-(4-(2-(tert-butyldiphenylsilyloxy)ethyl)piperazin-1-yl)-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethyl sulfonyl)phenylsulfonyl)-4-(4-((R)-(4'-chlorobiphenyl-2-yl)((S)-1,1-dimethylethylsulfinamido)methyl)piperidin-1-yl)benzamide

生成物 1

HCID 866618914-(4-((R)-(4'-chlorobiphenyl-2-yl)((S)-1,1-dimethylethylsulfinamido)methyl)piperidin-1-yl)-N-(4-((R)-4-(4-(2-hydroxyethyl)piperazin-1-yl)-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)phenylsulfonyl)benzamide収率 128.1%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

A solution of TASF (0.58 ml. 0.58 mmol, 1.0M in DMF) was added to a solution of N-(4-((R)-4-(4-(2-(tert-butyldiphenylsilyloxy)ethyl)piperazin-1-yl)-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethyl sulfonyl)phenylsulfonyl)-4-(4-((R)-(4′-chlorobiphenyl-2-yl)((S)-1,1-dimethylethylsulfinamido)methyl)piperidin-1-yl)benzamide (EXAMPLE 13, STEP 2, 0.39 g, 0.29 mmol) in DMF (2.3 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, after filtration, 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-(4-(2-hydroxyethyl)piperazin-1-yl)-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)phenylsulfonyl)benzamide (EXAMPLE 13, STEP 2, 0.41 g) which was used in the preparation of EXAMPLE 13, 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. filtrationafter filtration
  7. customdried under vacuum

出典と根拠

ORDレコード
ord-e5356db35301489ca39185894924ecbb
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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