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 1476335노트

반응식

HRID 1476335 반응식
[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

참가 물질

7

반응물 4

HCID 111,2-DichloroethaneHCID 81531DiisopropylethylamineHCID 250584544-[[(1R)-3-(4-Morpholinyl)-1-[(phenylthio)methyl]propyl]amino]-3-[(trifluoromethyl)sulfonyl]benzenesulfonamide2회HCID 580801654-(4-((R)-(4'-chlorobiphenyl-2-yl)((S)-1,1-dimethylethylsulfinamido)methyl)piperidin-1-yl)benzoic acid2회

생성물 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)benzamide수율 69%

시약·촉매·용매 2

HCID 142844-(Dimethylamino)pyridine촉매HCID 6344Dichloromethane용매3회

실험 절차

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%).

후처리

  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))

출처 및 근거

ORD 기록
ord-c5176dd392b0423aa6365795e4fe729a
출처 데이터셋
uspto-grants-2015_04
특허 번호
US09018381B2

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