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Dimethylformamide → 2-(3-methyl-2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindole-5-carbonitrile

HRID 63417
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HRID 63417 반응식
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[C:7](=[O:11])[N:6]([C:12]1([CH3:20])[CH2:17][CH2:16][C:15](=[O:18])[NH:14][C:13]1=[O:19])[CH2:5]2.[CH3:21][N:22](C)C=O>[C-]#N.[C-]#N.[Zn+2].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2]>[CH3:20][C:12]1([N:6]2[CH2:5][C:4]3[C:8](=[CH:9][CH:10]=[C:2]([C:21]#[N:22])[CH:3]=3)[C:7]2=[O:11])[CH2:17][CH2:16][C:15](=[O:18])[NH:14][C:13]1=[O:19]
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참가 물질

6

반응물 2

HCID 6228DimethylformamideHCID 690515003-(5-Bromo-1-oxoisoindolin-2-yl)-3-methylpiperidine-2,6-dione

생성물 1

HCID 670233462-(3-methyl-2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindole-5-carbonitrile수율 99%

시약·촉매·용매 3

HCID 11186Zinc cyanide (Zn(CN)2)촉매HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)
촉매
HCID 9811564Bis(dibenzylideneacetone)palladium촉매

반응 조건

온도
130 °C

실험 절차

A stirred mixture of 3-(5-bromo-1-oxo-1,3-dihydro-isoindol-2-yl)-3-methyl-piperidine-2,6-dione (1.40 g, 4.00 mmol), Zn(CN)2 (0.28 g, 2.40 mmol), Pd2(dba)3 (0.07 g, 0.08 mmol) and dppf (0.09 g, 0.16 mmol) in deoxygenated N,N-dimethylformamide (30 mL) was heated to 130° C. under nitrogen. After 2 h, the solvent was removed in vacuo and the residue was triturated in water (30 mL) then ethyl acetate hexanes (1:1, 30 mL). The product was isolated by filtration, washed with ethyl acetate hexanes (1:1) and dried in vacuo providing 2-(3-methyl-2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindole-5-carbonitrile (1.2 g, 99% yield); 1H NMR (DMSO-d6) δ 1.67 (s, 3H), 1.89-1.95 (m, 1H), 2.55-2.81 (m, 3H), 4.73 (d, J=18.2 Hz, 1H), 7.82 (d, J=7.8 Hz, 1H), 7.97 (d, J=7.8 Hz, 1H), 8.17 (s, 1H), 10.93 (s, 1H).

후처리

  1. customthe solvent was removed in vacuo
  2. customthe residue was triturated in water (30 mL)
  3. customThe product was isolated by filtration
  4. washwashed with ethyl acetate hexanes (1:1)
  5. customdried in vacuo

출처 및 근거

ORD 기록
ord-b5f8e9f880b245de82d48543c8b83f62
출처 데이터셋
uspto-grants-2016_09
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09447070B2

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