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

HRID 1476345
Notes
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Reaction equation

HRID 1476345 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]([CH3:102])[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]([CH3:80])([CH3:79])[CH3:78])=[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]([CH2:36][CH2:35][OH:34])[CH3:102])[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
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

4

Reactant 2

HCID 9795567Tris(dimethylamino)sulfonium difluorotrimethylsilicateHCID 86661887N-(4-((R)-4-((2-(tert-butyldiphenylsilyloxy)ethyl)(methyl)amino)-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 86661888
4-(4-((R)-(4'-chlorobiphenyl-2-yl)((S)-1,1-dimethylethylsulfinamido)methyl)piperidin-1-yl)-N-(4-((R)-4-((2-hydroxyethyl)(methyl)amino)-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)phenylsulfonyl)benzamide
Yield 119.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of TASF (0.40 ml. 0.40 mmol, 1.0M in DMF) was added to a solution of N-(4-((R)-4-((2-(tert-butyldiphenylsilyloxy)ethyl)(methyl)amino)-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 11, STEP 1, 0.26 g, 0.20 mmol) in DMF (1.6 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-((2-hydroxyethyl)(methyl)amino)-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)phenylsulfonyl)benzamide (EXAMPLE 11, STEP 2, 0.25 g) which was used in the preparation of EXAMPLE 11, 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. customdried under vacuum

Sources & evidence

ORD record
ord-8c6d8f7bf220495fa78c86907d778121
Source dataset
uspto-grants-2015_04
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09018381B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes