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Hydrochloric Acid → 4'-{[4-(1,4-Dioxaspiro[4.5]dec-8-yl)-5-oxo-7-propyl-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl]methyl}-3'-fluorobiphenyl-2-carbonitrile

HRID 519550
ノート
印刷プレビュー

反応式

HRID 519550 の反応式
[C:1]([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[CH:14]=[CH:13][C:12]([CH2:15][CH:16]([C:22](=O)[CH2:23][CH2:24][CH3:25])[C:17](OCC)=[O:18])=[C:11]([F:27])[CH:10]=1)#[N:2].[O:28]1[C:32]2([CH2:37][CH2:36][CH:35]([NH:38][C:39]3[NH:43][CH:42]=[N:41][N:40]=3)[CH2:34][CH2:33]2)[O:31][CH2:30][CH2:29]1.N12CCCN=C1CCCCC2.Cl>C(N(CC)C1C=CC=CC=1)C.C(OCC)(=O)C>[O:28]1[C:32]2([CH2:33][CH2:34][CH:35]([N:38]3[C:17](=[O:18])[C:16]([CH2:15][C:12]4[CH:13]=[CH:14][C:9]([C:4]5[C:3]([C:1]#[N:2])=[CH:8][CH:7]=[CH:6][CH:5]=5)=[CH:10][C:11]=4[F:27])=[C:22]([CH2:23][CH2:24][CH3:25])[N:40]4[N:41]=[CH:42][N:43]=[C:39]34)[CH2:36][CH2:37]2)[O:31][CH2:30][CH2:29]1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

7

反応物 4

HCID 313Hydrochloric Acid2 回HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 57460949Ethyl 2-[(2'-cyano-3-fluorobiphenyl-4-yl)methyl]-3-oxohexanoateHCID 178420920N-(1,4-dioxaspiro[4.5]dec-8-yl)-4H-1,2,4-triazol-3-amine

生成物 1

HCID 670090304'-{[4-(1,4-Dioxaspiro[4.5]dec-8-yl)-5-oxo-7-propyl-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl]methyl}-3'-fluorobiphenyl-2-carbonitrile
収率 84%

試薬・触媒・溶媒 2

HCID 7061N,N-Diethylaniline溶媒2 回HCID 8857Ethyl Acetate溶媒2 回

反応条件

温度
180 °C

実験手順

A mixture of ethyl 2-[(2′-cyano-3-fluorobiphenyl-4-yl)methyl]-3-oxohexanoate (408 g) and N-(1,4-dioxaspiro[4.5]dec-8-yl)-4H-1,2,4-triazol-3-amine (125 g) were dissolved in N,N-diethylaniline (1.5 L) at 160° C. (internal temperature). A solution of 1,8-diazabicyclo[5.4.0]undec-7-ene (38 mL) in N,N-diethylaniline (400 mL) was added dropwise over 30 min, and the mixture was stirred at 180° C. (internal temperature) for 22 hr. The reaction mixture was cooled to room temperature, and ethyl acetate (1 L) and 3M hydrochloric acid (1 L) were added. The mixture was transferred into a separatory funnel with ethyl acetate (2 L) and 3M hydrochlorid acid (1 L). The organic layer was successively washed with 3M hydrochloric acid (2 L) twice and brine (2 L), dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel chromatography to give the title compound as a brown solid (246 g, 84%).

後処理

  1. temperatureThe reaction mixture was cooled to room temperature
  2. washThe organic layer was successively washed with 3M hydrochloric acid (2 L) twice
  3. dry with materialbrine (2 L), dried over anhydrous magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe obtained residue was purified by silica gel chromatography

出典と根拠

ORDレコード
ord-dadfdbc8d07c417cb3d414a8a966d3d2
出典データセット
uspto-grants-2015_08
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09115136B2

反応ノート

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