1,2-Dichloroethane → N-(4-((R)-4-(4-(2-(tert-butyldiphenylsilyloxy)ethyl)piperazin-1-yl)-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

HRID 1476348ノート

反応式

HRID 1476348 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.[Si:50]([O:67][CH2:68][CH2:69][N:70]1[CH2:75][CH2:74][N:73]([CH2:76][CH2:77][C@@H:78]([NH:87][C:88]2[CH:93]=[CH:92][C:91]([S:94]([NH2:97])(=[O:96])=[O:95])=[CH:90][C:89]=2[S:98]([C:101]([F:104])([F:103])[F:102])(=[O:100])=[O:99])[CH2:79][S:80][C:81]2[CH:86]=[CH:85][CH:84]=[CH:83][CH:82]=2)[CH2:72][CH2:71]1)([C:63]([CH3:66])([CH3:65])[CH3:64])([C:57]1[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=1)[C:51]1[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=1>CN(C1C=CN=CC=1)C.C(Cl)Cl>[Si:50]([O:67][CH2:68][CH2:69][N:70]1[CH2:75][CH2:74][N:73]([CH2:76][CH2:77][C@@H:78]([NH:87][C:88]2[CH:93]=[CH:92][C:91]([S:94]([NH:97][C:25](=[O:26])[C:24]3[CH:28]=[CH:29][C:21]([N:18]4[CH2:19][CH2:20][CH:15]([C@H:14]([C:9]5[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=5[C:5]5[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=5)[NH:30][S@:31]([C:33]([CH3:36])([CH3:35])[CH3:34])=[O:32])[CH2:16][CH2:17]4)=[CH:22][CH:23]=3)(=[O:95])=[O:96])=[CH:90][C:89]=2[S:98]([C:101]([F:102])([F:104])[F:103])(=[O:99])=[O:100])[CH2:79][S:80][C:81]2[CH:86]=[CH:85][CH:84]=[CH:83][CH:82]=2)[CH2:72][CH2:71]1)([C:63]([CH3:64])([CH3:65])[CH3:66])([C:57]1[CH:58]=[CH:59][CH:60]=[CH:61][CH:62]=1)[C:51]1[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=1

参加物

7

反応物 4

HCID 111,2-DichloroethaneHCID 81531DiisopropylethylamineHCID 580801654-(4-((R)-(4'-chlorobiphenyl-2-yl)((S)-1,1-dimethylethylsulfinamido)methyl)piperidin-1-yl)benzoic acid2 回HCID 66723648(R)-4-(4-(4-(2-(tert-Butyldiphenylsilyloxy)ethyl)piperazin-1-yl)-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)benzenesulfonamide2 回

生成物 1

HCID 86661892N-(4-((R)-4-(4-(2-(tert-butyldiphenylsilyloxy)ethyl)piperazin-1-yl)-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収率 102.8%

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 15 min. A solution of (R)-4-(4-(4-(2-(tert-butyldiphenylsilyloxy)ethyl)piperazin-1-yl)-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)benzenesulfonamide (INTERMEDIATE 22, 0.24 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 reaction mixture was diluted with DCM and washed with sodium bisulfate (1N, aq.) followed by sodium bicarbonate (saturated, aq.). The organic layer was dried (Na2SO4), filtered, and evaporated under reduced pressure to give a residue which was dried under vacuum to provide N-(4-((R)-4-(4-(2-(tert-butyldiphenylsilyloxy)ethyl)piperazin-1-yl)-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)phenylsulfonyl)-4-(4-((R)-(4′-chlorobiphenyl-2-yl)((S)-1,1-dimethylethylsulfinamido)methyl)piperidin-1-yl)benzamide (EXAMPLE 13, STEP 1, 0.40 g) which was used in the preparation of EXAMPLE 13, STEP 2, without further purification.

後処理

  1. customflushed with nitrogen
  2. stirringthe reaction mixture was stirred at r.t overnight
  3. washwashed with sodium bisulfate (1N, 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 dried under vacuum

出典と根拠

ORDレコード
ord-8f8f3c18a51f4364abd15c4cad36a96f
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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