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 1476335ノート

反応式

HRID 1476335 の反応式
[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

参加物

7

反応物 4

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

生成物 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)benzamide収率 69%

試薬・触媒・溶媒 2

HCID 142844-(Dimethylamino)pyridine触媒HCID 6344Dichloromethane溶媒3 回

実験手順

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%).

後処理

  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))

出典と根拠

ORDレコード
ord-c5176dd392b0423aa6365795e4fe729a
出典データセット
uspto-grants-2015_04
特許番号
US09018381B2

反応ノート

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