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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
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HRID 519550 반응식
[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
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참가 물질

7

반응물 4

HCID 313Hydrochloric Acid2회HCID 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

생성물 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
수율 84%

시약·촉매·용매 2

HCID 7061N,N-Diethylaniline용매2회HCID 8857Ethyl Acetate용매2회

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온도
180 °C

실험 절차

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%).

후처리

  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

출처 및 근거

ORD 기록
ord-dadfdbc8d07c417cb3d414a8a966d3d2
출처 데이터셋
uspto-grants-2015_08
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09115136B2

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