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Dimethylformamide → tert-Butyl 7-cyano-1-[1-(pyridin-2-yl)cyclobutyl]-3,4-dihydroisoquinoline-2(1H)-carboxylate

HRID 242108
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HRID 242108 반응식
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1([CH:11]2[C:20]3[C:15](=[CH:16][CH:17]=[C:18](OS(C(F)(F)F)(=O)=O)[CH:19]=3)[CH2:14][CH2:13][N:12]2[C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:10][CH2:9][CH2:8]1.[CH3:36][N:37](C)C=O>C1(P([C-]2C=CC=C2)C2C=CC=CC=2)C=CC=CC=1.[CH-]1C=CC=C1.[Fe+2].[C-]#N.[Zn+2].[C-]#N>[C:36]([C:18]1[CH:19]=[C:20]2[C:15]([CH2:14][CH2:13][N:12]([C:29]([O:31][C:32]([CH3:35])([CH3:33])[CH3:34])=[O:30])[CH:11]2[C:7]2([C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=3)[CH2:10][CH2:9][CH2:8]2)=[CH:16][CH:17]=1)#[N:37]
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참가 물질

5

반응물 2

HCID 6228DimethylformamideHCID 58246194tert-Butyl 1-[1-(pyridin-2-yl)cyclobutyl]-7-{[(trifluoromethyl)sulfonyl]oxy}-3,4-dihydroisoquinoline-2(1H)-carboxylate

생성물 1

HCID 58246239tert-Butyl 7-cyano-1-[1-(pyridin-2-yl)cyclobutyl]-3,4-dihydroisoquinoline-2(1H)-carboxylate

시약·촉매·용매 2

HCID 11186Zinc cyanide (Zn(CN)2)촉매
HCID 15826098
Cyclopenta-1,3-diene;cyclopenta-2,4-dien-1-yl(diphenyl)phosphane;iron(2+)
촉매

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온도
90 °C

실험 절차

Dipalladium trisdibenzylidene acetone (0.14 g, 0.153 mmol) and diphenylphosphinoferrocene (0.338 g, 0.61 mmol) were suspended in dimethylformamide (15 ml) under an argon atmosphere. tert-Butyl 1-[1-(pyridin-2-yl)cyclobutyl]-7-{[(trifluoromethyl)sulfonyl]oxy}-3,4-dihydroisoquinoline-2(1H)-carboxylate (0.782 g, 1.562 mmol) was added and the reaction mixture was heated to 90° C. Zinc cyanide (0.215 g, 1.831 mmol) was added over 30 min in small portions. Stirring at 90° C. was continued for 15 min. After cooling to room temperature the catalyst was removed by filtration and washed with dimethylformamide. The dimethylformamide filtrate was poured in water (200 ml). The water was extracted with dichloromethane (3×). The combined organic extracts were washed with water, dried (MgSO4) and concentrated in vacuo. The crude product was purified by flash chromatography (silica, dichloromethane, methanol). Yield: 197 mg (0.506 mmol, 33%).

후처리

  1. temperatureAfter cooling to room temperature the catalyst
  2. customwas removed by filtration
  3. washwashed with dimethylformamide
  4. additionThe dimethylformamide filtrate was poured in water (200 ml)
  5. extractionThe water was extracted with dichloromethane (3×)
  6. washThe combined organic extracts were washed with water
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated in vacuo
  9. customThe crude product was purified by flash chromatography (silica, dichloromethane, methanol)

출처 및 근거

ORD 기록
ord-4d3258f937c347e395c5fd2d4b189554
출처 데이터셋
uspto-grants-2014_02
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08653100B2

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