Tetrabutylammonium Fluoride → 4-(4-((R)-(4'-chlorobiphenyl-2-yl)(hydroxy)methyl)piperidin-1-yl)-N-(4-((R)-4-((S)-3-((diethylamino)methyl)morpholino)-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)phenylsulfonyl)benzamide

HRID 1476353Notes

Reaction equation

HRID 1476353 reaction equation
[Si]([O:8][C@@H:9]([C:65]1[CH:70]=[CH:69][CH:68]=[CH:67][C:66]=1[C:71]1[CH:76]=[CH:75][C:74]([Cl:77])=[CH:73][CH:72]=1)[CH:10]1[CH2:15][CH2:14][N:13]([C:16]2[CH:64]=[CH:63][C:19]([C:20]([NH:22][S:23]([C:26]3[CH:31]=[CH:30][C:29]([NH:32][C@H:33]([CH2:42][CH2:43][N:44]4[CH2:49][CH2:48][O:47][CH2:46][C@@H:45]4[CH2:50][N:51]([CH2:54][CH3:55])[CH2:52][CH3:53])[CH2:34][S:35][C:36]4[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=4)=[C:28]([S:56]([C:59]([F:62])([F:61])[F:60])(=[O:58])=[O:57])[CH:27]=3)(=[O:25])=[O:24])=[O:21])=[CH:18][CH:17]=2)[CH2:12][CH2:11]1)(C(C)(C)C)(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>>[Cl:77][C:74]1[CH:75]=[CH:76][C:71]([C:66]2[CH:67]=[CH:68][CH:69]=[CH:70][C:65]=2[C@H:9]([OH:8])[CH:10]2[CH2:15][CH2:14][N:13]([C:16]3[CH:17]=[CH:18][C:19]([C:20]([NH:22][S:23]([C:26]4[CH:31]=[CH:30][C:29]([NH:32][C@H:33]([CH2:42][CH2:43][N:44]5[CH2:49][CH2:48][O:47][CH2:46][C@@H:45]5[CH2:50][N:51]([CH2:54][CH3:55])[CH2:52][CH3:53])[CH2:34][S:35][C:36]5[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=5)=[C:28]([S:56]([C:59]([F:62])([F:61])[F:60])(=[O:57])=[O:58])[CH:27]=4)(=[O:24])=[O:25])=[O:21])=[CH:63][CH:64]=3)[CH2:12][CH2:11]2)=[CH:72][CH:73]=1

Participants

3

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 866618974-(4-((R)-(tert-butyldimethylsilyloxy)(4'-chlorobiphenyl-2-yl)methyl)piperidin-1-yl)-N-(4-((R)-4-((S)-3-((diethylamino)methyl)morpholino)-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)phenylsulfonyl)benzamide

Product 1

HCID 866618964-(4-((R)-(4'-chlorobiphenyl-2-yl)(hydroxy)methyl)piperidin-1-yl)-N-(4-((R)-4-((S)-3-((diethylamino)methyl)morpholino)-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)phenylsulfonyl)benzamideYield 48%

Procedure

A solution of 4-(4-((R)-(tert-butyldimethylsilyloxy)(4′-chlorobiphenyl-2-yl)methyl)piperidin-1-yl)-N-(4-((R)-4-((S)-3-((diethylamino)methyl)morpholino)-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethyl sulfonyl)phenylsulfonyl)benzamide, (INTERMEDIATE 89, 100 mg, 0.09 mmol) and TBAF (3.5 ml 3.46 mmol, 1 M in THF) was stirred for 45 minutes at room temperature. The solvent was removed under reduced pressure and the residue was taken up in DCM (50 ml). The organic layer was washed successively with 50 ml of water (50 ml) and saturated aqueous sodium bicarbonate (50 ml). The organic phase was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The concentrate was purified by column chromatography (ISCO, eluting with 0→100% DCM/[10% 2N ammonia in MeOH in DCM] over 19 minutes and then eluting with 0→20% MeOH/DCM) to give the title product (43.0 mg, yield: 48%).

Workup

  1. customThe solvent was removed under reduced pressure
  2. washThe organic layer was washed successively with 50 ml of water (50 ml) and saturated aqueous sodium bicarbonate (50 ml)
  3. dry with materialThe organic phase was dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe concentrate was purified by column chromatography (ISCO
  7. washeluting with 0→100% DCM/[10% 2N ammonia in MeOH in DCM] over 19 minutes
  8. washeluting with 0→20% MeOH/DCM)

Sources & evidence

ORD record
ord-d93dd631cbf044aea2a671bf7e7e4d13
Source dataset
uspto-grants-2015_04
Patent number
US09018381B2

Reaction notes

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