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1,2-Dichloroethane → 4-(4-((S)-(4'-chlorobiphenyl-2-yl)(hydroxy)methyl)piperidin-1-yl)-N-(4-((R)-4-morpholino-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)phenylsulfonyl)benzamide

HRID 1476350
ノート
印刷プレビュー

反応式

HRID 1476350 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]([OH:30])[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.[O:31]1[CH2:36][CH2:35][N:34]([CH2:37][CH2:38][C@@H:39]([NH:48][C:49]2[CH:54]=[CH:53][C:52]([S:55]([NH2:58])(=[O:57])=[O:56])=[CH:51][C:50]=2[S:59]([C:62]([F:65])([F:64])[F:63])(=[O:61])=[O:60])[CH2:40][S:41][C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)[CH2:33][CH2:32]1.C(Cl)CCl>CN(C1C=CN=CC=1)C>[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]([OH:30])[CH:15]2[CH2:20][CH2:19][N:18]([C:21]3[CH:22]=[CH:23][C:24]([C:25]([NH:58][S:55]([C:52]4[CH:53]=[CH:54][C:49]([NH:48][C@H:39]([CH2:38][CH2:37][N:34]5[CH2:35][CH2:36][O:31][CH2:32][CH2:33]5)[CH2:40][S:41][C:42]5[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=5)=[C:50]([S:59]([C:62]([F:65])([F:63])[F:64])(=[O:61])=[O:60])[CH:51]=4)(=[O:56])=[O:57])=[O:26])=[CH:28][CH:29]=3)[CH2:17][CH2:16]2)=[CH:6][CH:7]=1
参加物実験手順後処理出典と根拠反応ノート

参加物

5

反応物 3

HCID 111,2-DichloroethaneHCID 250584544-[[(1R)-3-(4-Morpholinyl)-1-[(phenylthio)methyl]propyl]amino]-3-[(trifluoromethyl)sulfonyl]benzenesulfonamide2 回HCID 58080142(S)-4-(4-((4'-Chlorobiphenyl-2-yl)(hydroxy)methyl)piperidin-1-yl)benzoic acid2 回

生成物 1

HCID 866618934-(4-((S)-(4'-chlorobiphenyl-2-yl)(hydroxy)methyl)piperidin-1-yl)-N-(4-((R)-4-morpholino-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)phenylsulfonyl)benzamide
収率 41.5%

試薬・触媒・溶媒 1

HCID 142844-(Dimethylamino)pyridine触媒

実験手順

(S)-4-(4-((4′-Chlorobiphenyl-2-yl)(hydroxy)methyl)piperidin-1-yl)benzoic acid (INTERMEDIATE 70, 137.4 mg, 0.33 mmol), (R)-4-(4-morpholino-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)benzenesulfonamide (INTERMEDIATE 69, 190.3 mg, 0.34 mmol), DMAP (81.0 mg, 0.66 mmol), and EDC (134.5 mg, 0.70 mmol) were placed in a 50 ml flask and flushed with nitrogen. DCM (6.5 ml) was added, and the solution was stirred at room temperature overnight. The reaction mixture was diluted with DCM (40 ml) and washed with 1N aq. sodium bisulfate (35 ml) followed by a saturated aq. sodium bicarbonate (40 ml). The organic layer was dried (Na2SO4), filtered, and evaporated under reduced pressure. The concentrate was purified by column chromatography (ISCO, 12 g silica gel column, eluting with 0→10% MeOH in DCM). Clean fractions were combined, evaporated under vacuum, and dried overnight in a 40° C. vacuum oven to provide the title product as a substantially separated isomer (129.3 mg, yield: 41.5%).

後処理

  1. customflushed with nitrogen
  2. additionDCM (6.5 ml) was added
  3. additionThe reaction mixture was diluted with DCM (40 ml)
  4. washwashed with 1N aq. sodium bisulfate (35 ml)
  5. dry with materialThe organic layer was dried (Na2SO4)
  6. filtrationfiltered
  7. customevaporated under reduced pressure
  8. customThe concentrate was purified by column chromatography (ISCO, 12 g silica gel column, eluting with 0→10% MeOH in DCM)
  9. customevaporated under vacuum
  10. customdried overnight in a 40° C. vacuum oven

出典と根拠

ORDレコード
ord-0c04850b658c4c6b950f7998d7d50fae
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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