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Diisopropylethylamine → (1,1-Dioxo-thiomorpholin-4-yl)-[5-(1-isopropyl-piperidin-4-yloxy)-1-(2,2,2-trifluoro-ethyl)-1H-indol-2-yl]-methanone

HRID 493985
ノート
印刷プレビュー

反応式

HRID 493985 の反応式
[CH:1]([N:4]1[CH2:9][CH2:8][CH:7]([O:10][C:11]2[CH:12]=[C:13]3[C:17](=[CH:18][CH:19]=2)[N:16]([CH2:20][C:21]([F:24])([F:23])[F:22])[C:15]([C:25]([OH:27])=O)=[CH:14]3)[CH2:6][CH2:5]1)([CH3:3])[CH3:2].[Cl-].[Li+].[NH:30]1[CH2:35][CH2:34][S:33](=[O:37])(=[O:36])[CH2:32][CH2:31]1.C(N(C(C)C)CC)(C)C>CN(C)C=O>[O:36]=[S:33]1(=[O:37])[CH2:34][CH2:35][N:30]([C:25]([C:15]2[N:16]([CH2:20][C:21]([F:22])([F:24])[F:23])[C:17]3[C:13]([CH:14]=2)=[CH:12][C:11]([O:10][CH:7]2[CH2:8][CH2:9][N:4]([CH:1]([CH3:3])[CH3:2])[CH2:5][CH2:6]2)=[CH:19][CH:18]=3)=[O:27])[CH2:31][CH2:32]1
参加物実験手順後処理出典と根拠反応ノート

参加物

6

反応物 4

HCID 81531DiisopropylethylamineHCID 433294Lithium ChlorideHCID 6484228Thiomorpholine 1,1-dioxideHCID 67073105HCID 67073105、化合物

生成物 1

HCID 16112805(1,1-Dioxo-thiomorpholin-4-yl)-[5-(1-isopropyl-piperidin-4-yloxy)-1-(2,2,2-trifluoro-ethyl)-1H-indol-2-yl]-methanone収率 66%

試薬・触媒・溶媒 1

HCID 6228
Dimethylformamide
溶媒

実験手順

A mixture of 5-(1-isopropyl-piperidin-4-yloxy)-1-(2,2,2-trifluoro-ethyl)-1H-indole-2-carboxylic acid, hydrochloric salt with one equivalent of lithium chloride (650 mg, 1.0 eq.), 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethylurunium tetrafluoroborate (563 mg, 1.2 eq.), thiomorpholine-1,1-dioxide (purchased at Syntec, ref. M1201) and diisopropylethylamine (1.22 mL, 5 eq.) in dimethylformamide was stirred at room temperature for 24 h and then partitioned between an aqueous solution of sodium hydrogenocarbonate and ethyl acetate. The aqueous layer was extracted with ethyl acetate and the combined organic layers were washed with water and brine, dried over sodium sulfate, filtered, evaporated in vacuo and purified on silica eluting with dichloromethane/methanol/ammoniac. One fraction was isolated and dried in vacuo, to yield 468 mg (66%) of the desired product as off-white solid. MS (m/e): 502.5 (MH+, 100%).

後処理

  1. custompartitioned between an aqueous solution of sodium hydrogenocarbonate and ethyl acetate
  2. extractionThe aqueous layer was extracted with ethyl acetate
  3. washthe combined organic layers were washed with water and brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. custompurified on silica eluting with dichloromethane/methanol/ammoniac
  8. customOne fraction was isolated
  9. customdried in vacuo

出典と根拠

ORDレコード
ord-1e45d9c906104cf78d1afcebaebf6953
出典データセット
uspto-grants-2009_05
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07538101B2

反応ノート

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