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 1476349Notes

Reaction equation

HRID 1476349 reaction equation
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

Participants

4

Reactant 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

Product 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)benzamideYield 128.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-e5356db35301489ca39185894924ecbb
Source dataset
uspto-grants-2015_04
Patent number
US09018381B2

Reaction notes

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