Diisopropylethylamine → (3R)-3-[(2-Chloro-benzoyl)amino]-N-methyl-N-[1-(2-methylamino-pyrimidin-4-yl)-piperidin-4-yl]-2,3-dihydro-1H-indene-5-carboxylic acid amide

HRID 1193425ノート

反応式

HRID 1193425 の反応式
[Cl:1][C:2]1[CH:29]=[CH:28][CH:27]=[CH:26][C:3]=1[C:4]([NH:6][C@H:7]1[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([C:16]([N:18]([CH3:25])[CH:19]3[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]3)=[O:17])[CH:14]=2)[CH2:9][CH2:8]1)=[O:5].Cl[C:31]1[CH:36]=[CH:35][N:34]=[C:33](CN)[N:32]=1.C[CH2:40][N:41](C(C)C)C(C)C>O1CCOCC1>[Cl:1][C:2]1[CH:29]=[CH:28][CH:27]=[CH:26][C:3]=1[C:4]([NH:6][C@H:7]1[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([C:16]([N:18]([CH3:25])[CH:19]3[CH2:20][CH2:21][N:22]([C:35]4[CH:36]=[CH:31][N:32]=[C:33]([NH:41][CH3:40])[N:34]=4)[CH2:23][CH2:24]3)=[O:17])[CH:14]=2)[CH2:9][CH2:8]1)=[O:5]

参加物

5

反応物 3

HCID 81531DiisopropylethylamineHCID 22460689(4-Chloropyrimidin-2-YL)methanamineHCID 66798745(R)-3-(2-chlorobenzamido)-N-methyl-N-(piperidin-4-yl)-2,3-dihydro-1H-indene-5-carboxamide

生成物 1

HCID 66798485(3R)-3-[(2-Chloro-benzoyl)amino]-N-methyl-N-[1-(2-methylamino-pyrimidin-4-yl)-piperidin-4-yl]-2,3-dihydro-1H-indene-5-carboxylic acid amide収率 49%

試薬・触媒・溶媒 1

HCID 312751,4-Dioxane溶媒

実験手順

A mixture of (R)-3-(2-chlorobenzamido)-N-methyl-N-(piperidin-4-yl)-2,3-dihydro-1H-indene-5-carboxamide (400 mg, 0.973 mmol, 1 eq), (4-chloropyrimidin-2-yl)methylamine (280 mg, 1.946 mmol, 2 eq) and DIPEA (0.33 ml, 1.946 mmol, 2 eq) in dioxane (10 ml) was refluxed for 16 h. When the reaction was complete according to TLC monitoring, concentration under reduced pressure was carried out and the residue was taken up in dichloromethane (100 ml) and washed with water (40 ml) and saturated sodium chloride solution (40 ml). The organic phase was dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography (silica gel, 6% methanol in dichloromethane). The desired product was in the form of a white solid. Yield: 49% (250 mg, 0.482 mmol)

後処理

  1. temperaturewas refluxed for 16 h
  2. concentrationWhen the reaction was complete according to TLC monitoring, concentration under reduced pressure
  3. washwashed with water (40 ml) and saturated sodium chloride solution (40 ml)
  4. dry with materialThe organic phase was dried over sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe crude product was purified by column chromatography (silica gel, 6% methanol in dichloromethane)

出典と根拠

ORDレコード
ord-6bcc00b5450949dc97599b25f3778581
出典データセット
uspto-grants-2014_03
特許番号
US08680159B2

反応ノート

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