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1,2-二氯乙烷 → N-(4-((R)-4-((2-(tert-butyldiphenylsilyloxy)ethyl)(methyl)amino)-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 1771237
笔记
打印预览

反应方程式

HRID 1771237 反应方程式
[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]([CH3:100])[CH2:71][CH2:72][C@@H:73]([NH:82][C:83]1[CH:88]=[CH:87][C:86]([S:89]([NH2:92])(=[O:91])=[O:90])=[CH:85][C:84]=1[S:93]([C:96]([F:99])([F:98])[F:97])(=[O:95])=[O:94])[CH2:74][S:75][C:76]1[CH:81]=[CH:80][CH:79]=[CH:78][CH:77]=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]([CH3:100])[CH2:71][CH2:72][C@@H:73]([NH:82][C:83]1[CH:88]=[CH:87][C:86]([S:89]([NH:92][C:25](=[O:26])[C:24]2[CH:28]=[CH:29][C:21]([N:18]3[CH2:19][CH2:20][CH:15]([C@H:14]([C:9]4[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=4[C:5]4[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=4)[NH:30][S@:31]([C:33]([CH3:36])([CH3:35])[CH3:34])=[O:32])[CH2:16][CH2:17]3)=[CH:22][CH:23]=2)(=[O:90])=[O:91])=[CH:85][C:84]=1[S:93]([C:96]([F:98])([F:99])[F:97])(=[O:94])=[O:95])[CH2:74][S:75][C:76]1[CH:81]=[CH:80][CH:79]=[CH:78][CH:77]=1)([C:63]([CH3:64])([CH3:66])[CH3:65])([C:51]1[CH:52]=[CH:53][CH:54]=[CH:55][CH:56]=1)[C:57]1[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=1
参与物实验过程后处理来源与证据反应笔记

参与物

7

反应物 4

HCID 111,2-二氯乙烷HCID 81531N,N-二异丙基乙胺HCID 580801654-(4-((R)-(4'-chlorobiphenyl-2-yl)((S)-1,1-dimethylethylsulfinamido)methyl)piperidin-1-yl)benzoic acid2 次HCID 66723910(R)-4-(4-((2-(tert-butyldiphenylsilyloxy)ethyl)(methyl)amino)-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)benzenesulfonamide2 次

产物 1

HCID 86661887
N-(4-((R)-4-((2-(tert-butyldiphenylsilyloxy)ethyl)(methyl)amino)-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
收率 87.8%

试剂、催化剂与溶剂 2

HCID 142844-二甲氨基吡啶(DMAP)催化剂HCID 6344二氯甲烷溶剂3 次

实验过程

4-(4-((R)-(4′-chlorobiphenyl-2-yl)((S)-1,1-dimethylethylsulfinamido)methyl)piperidin-1-yl)benzoic acid (INTERMEDIATE 130, 0.12 g, 0.23 mmol), DMAP (56 mg, 0.46 mmol), and EDC (88 mg, 0.46 mmol) were placed in a 40 ml vial and flushed with nitrogen. DCM (3.0 ml) and DIPEA (0.08 ml, 0.46 mmol) were added and the solution was stirred at r.t for 15 min. A solution of (R)-4-(4-((2-(tert-butyldiphenylsilyloxy)ethyl)(methyl)amino)-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)benzenesulfonamide (INTERMEDIATE 28, 0.178 g, 0.23 mmol) in DCM (1.5 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 a 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-((2-(tert-butyldiphenylsilyloxy)ethyl)(methyl)amino)-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 11, STEP 1, 0.26 g) which was used in the preparation of EXAMPLE 11, STEP 2 without further purification.

后处理

  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

来源与证据

ORD记录
ord-fff94a4d74dc4ac886a99fb6a7a76546
来源数据集
uspto-grants-2016_02
DOI
10.6084/m9.figshare.5104873.v1
专利号
US09248140B2

反应笔记

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本页导航参与物实验过程后处理来源与证据反应笔记