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 1476349노트

반응식

HRID 1476349 반응식
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

참가 물질

4

반응물 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

생성물 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)benzamide수율 128.1%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-e5356db35301489ca39185894924ecbb
출처 데이터셋
uspto-grants-2015_04
특허 번호
US09018381B2

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