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Tetrabutylammonium Fluoride → 4-(4-((R)-(4'-chlorobiphenyl-2-yl)(hydroxy)methyl)piperidin-1-yl)-N-(4-((R)-4-morpholino-1-(phenylthio)butan-2-ylamino)-3-nitrophenylsulfonyl)benzamide

HRID 1476351
ノート
印刷プレビュー

反応式

HRID 1476351 の反応式
[Si]([O:8][C@@H:9]([C:55]1[CH:60]=[CH:59][CH:58]=[CH:57][C:56]=1[C:61]1[CH:66]=[CH:65][C:64]([Cl:67])=[CH:63][CH:62]=1)[CH:10]1[CH2:15][CH2:14][N:13]([C:16]2[CH:54]=[CH:53][C:19]([C:20]([NH:22][S:23]([C:26]3[CH:31]=[CH:30][C:29]([NH:32][C@H:33]([CH2:42][CH2:43][N:44]4[CH2:49][CH2:48][O:47][CH2:46][CH2:45]4)[CH2:34][S:35][C:36]4[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=4)=[C:28]([N+:50]([O-:52])=[O:51])[CH:27]=3)(=[O:25])=[O:24])=[O:21])=[CH:18][CH:17]=2)[CH2:12][CH2:11]1)(C(C)(C)C)(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>>[Cl:67][C:64]1[CH:65]=[CH:66][C:61]([C:56]2[CH:57]=[CH:58][CH:59]=[CH:60][C:55]=2[C@H:9]([OH:8])[CH:10]2[CH2:11][CH2:12][N:13]([C:16]3[CH:17]=[CH:18][C:19]([C:20]([NH:22][S:23]([C:26]4[CH:31]=[CH:30][C:29]([NH:32][C@H:33]([CH2:42][CH2:43][N:44]5[CH2:45][CH2:46][O:47][CH2:48][CH2:49]5)[CH2:34][S:35][C:36]5[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=5)=[C:28]([N+:50]([O-:52])=[O:51])[CH:27]=4)(=[O:25])=[O:24])=[O:21])=[CH:53][CH:54]=3)[CH2:14][CH2:15]2)=[CH:62][CH:63]=1
参加物実験手順後処理出典と根拠反応ノート

参加物

3

反応物 2

HCID 2724141Tetrabutylammonium FluorideHCID 866618754-(4-((R)-(tert-butyldimethylsilyloxy)(4'-chlorobiphenyl-2-yl)methyl)piperidin-1-yl)-N-(4-((R)-4-morpholino-1-(phenylthio)butan-2-ylamino)-3-nitrophenylsulfonyl)benzamide2 回

生成物 1

HCID 667237894-(4-((R)-(4'-chlorobiphenyl-2-yl)(hydroxy)methyl)piperidin-1-yl)-N-(4-((R)-4-morpholino-1-(phenylthio)butan-2-ylamino)-3-nitrophenylsulfonyl)benzamide収率 79.4%

実験手順

4-(4-((R)-(tert-butyldimethylsilyloxy)(4′-chlorobiphenyl-2-yl)methyl)piperidin-1-yl)-N-(4-((R)-4-morpholino-1-(phenylthio)butan-2-ylamino)-3-nitrophenylsulfonyl)benzamide (INTERMEDIATE 75, 329.0 mg, 0.33 mmol) was charged in a 100 ml flask under nitrogen and treated with TBAF (10.0 ml, 1.0 M in THF, 10 mmol). The resulting solution was stirred at room temperature for 35 minutes whereupon the volatiles were removed under reduced pressure. The concentrate was diluted with DCM (100 ml) and washed with 1N aq. NaHSO4 (100 ml), and saturated aq. NaHCO3 (30 ml), then dried (Na2SO4), filtered, and evaporated under vacuum. The concentrate was purified by column chromatography (ISCO, 12 g silica gel column, eluting with 0→5% MeOH/DCM) followed by further purification by column chromatography (ISCO, 12 g silica gel column, eluting with 0→90% DCM/[10% of 2M NH3 in MeOH/90% DCM]) to provide the title product (228 mg, yield: 78%)

後処理

  1. customwere removed under reduced pressure
  2. additionThe concentrate was diluted with DCM (100 ml)
  3. washwashed with 1N aq. NaHSO4 (100 ml), and saturated aq. NaHCO3 (30 ml)
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. customevaporated under vacuum
  7. customThe concentrate was purified by column chromatography (ISCO, 12 g silica gel column, eluting with 0→5% MeOH/DCM)
  8. customfollowed by further purification by column chromatography (ISCO, 12 g silica gel column, eluting with 0→90% DCM/[10% of 2M NH3 in MeOH/90% DCM])

出典と根拠

ORDレコード
ord-18914a074f464e19bef7bb6555ef0596
出典データセット
uspto-grants-2015_04
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09018381B2

反応ノート

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このページの内容参加物実験手順後処理出典と根拠反応ノート