1,2-Dichloroethane → 4-(4-((R)-(4'-chlorobiphenyl-2-yl)((S)-1,1-dimethylethylsulfinamido)methyl)piperidin-1-yl)-N-(4-((R)-4-morpholino-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)phenylsulfonyl)benzamide

HRID 1476335Notes

Reaction equation

HRID 1476335 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[C@H:14]([NH:30][S@:31]([C:33]([CH3:36])([CH3:35])[CH3:34])=[O:32])[CH:15]2[CH2:20][CH2:19][N:18]([C:21]3[CH:29]=[CH:28][C:24]([C:25](O)=[O:26])=[CH:23][CH:22]=3)[CH2:17][CH2:16]2)=[CH:4][CH:3]=1.C(Cl)CCl.CCN(C(C)C)C(C)C.[O:50]1[CH2:55][CH2:54][N:53]([CH2:56][CH2:57][C@@H:58]([NH:67][C:68]2[CH:73]=[CH:72][C:71]([S:74]([NH2:77])(=[O:76])=[O:75])=[CH:70][C:69]=2[S:78]([C:81]([F:84])([F:83])[F:82])(=[O:80])=[O:79])[CH2:59][S:60][C:61]2[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=2)[CH2:52][CH2:51]1>CN(C1C=CN=CC=1)C.C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[C@H:14]([NH:30][S@:31]([C:33]([CH3:34])([CH3:35])[CH3:36])=[O:32])[CH:15]2[CH2:16][CH2:17][N:18]([C:21]3[CH:22]=[CH:23][C:24]([C:25]([NH:77][S:74]([C:71]4[CH:72]=[CH:73][C:68]([NH:67][C@H:58]([CH2:57][CH2:56][N:53]5[CH2:54][CH2:55][O:50][CH2:51][CH2:52]5)[CH2:59][S:60][C:61]5[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=5)=[C:69]([S:78]([C:81]([F:83])([F:84])[F:82])(=[O:80])=[O:79])[CH:70]=4)(=[O:75])=[O:76])=[O:26])=[CH:28][CH:29]=3)[CH2:19][CH2:20]2)=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 111,2-DichloroethaneHCID 81531DiisopropylethylamineHCID 250584544-[[(1R)-3-(4-Morpholinyl)-1-[(phenylthio)methyl]propyl]amino]-3-[(trifluoromethyl)sulfonyl]benzenesulfonamide2×HCID 580801654-(4-((R)-(4'-chlorobiphenyl-2-yl)((S)-1,1-dimethylethylsulfinamido)methyl)piperidin-1-yl)benzoic acid2×

Product 1

HCID 866618804-(4-((R)-(4'-chlorobiphenyl-2-yl)((S)-1,1-dimethylethylsulfinamido)methyl)piperidin-1-yl)-N-(4-((R)-4-morpholino-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)phenylsulfonyl)benzamideYield 69%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent3×

Procedure

4-(4-((R)-(4′-chlorobiphenyl-2-yl)((S)-1,1-dimethylethylsulfinamido)methyl)piperidin-1-yl)benzoic acid (INTERMEDIATE 130, 0.150 g, 0.29 mmol), DMAP (70 mg, 0.57 mmol), and EDC (0.110 g, 0.57 mmol) were placed in a 40 ml vial and flushed with nitrogen. DCM (4.0 ml) and DIPEA (0.10 ml, 0.57 mmol) were added, and the solution was stirred at r.t for 10 minutes. A solution of (R)-4-(4-morpholino-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)benzenesulfonamide (INTERMEDIATE 69, 0.158 g, 0.29 mmol) in DCM (1.6 ml) was added to the solution and the reaction mixture was stirred at r.t overnight. The mixture was diluted with DCM and washed with 1N sodium bisulfate (aq.) followed by a saturated aq. sodium bicarbonate. The organic layer was dried (Na2SO4), filtered, and evaporated under reduced pressure to give a residue which was purified by column chromatography (ISCO, silica gel column, eluting with 0→100% DCM/MeOH/NH3 (10:1:0.1 v/v/v)) to provide the title compound (0.21 g, yield: 69%).

Workup

  1. customflushed with nitrogen
  2. stirringthe reaction mixture was stirred at r.t overnight
  3. washwashed with 1N sodium bisulfate (aq.)
  4. dry with materialThe organic layer was dried (Na2SO4)
  5. filtrationfiltered
  6. customevaporated under reduced pressure
  7. customto give a residue which
  8. customwas purified by column chromatography (ISCO, silica gel column, eluting with 0→100% DCM/MeOH/NH3 (10:1:0.1 v/v/v))

Sources & evidence

ORD record
ord-c5176dd392b0423aa6365795e4fe729a
Source dataset
uspto-grants-2015_04
Patent number
US09018381B2

Reaction notes

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