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Dimethylformamide → Ethyl 8-(benzyloxy)-6-cyano-2-(4-fluorobenzyl)-1-oxo-1,2,3,4-tetrahydropyrrolo[1,2-a]-pyrazine-7-carboxylate

HRID 494106
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HRID 494106 반응식
[CH2:1]([O:8][C:9]1[C:10]([C:28]([O:30][CH2:31][CH3:32])=[O:29])=[C:11](Br)[N:12]2[CH2:17][CH2:16][N:15]([CH2:18][C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=3)[C:14](=[O:26])[C:13]=12)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH3:52][N:53](C=O)C>[C-]#N.[Zn+2].[C-]#N.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]>[CH2:1]([O:8][C:9]1[C:10]([C:28]([O:30][CH2:31][CH3:32])=[O:29])=[C:11]([C:52]#[N:53])[N:12]2[CH2:17][CH2:16][N:15]([CH2:18][C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=3)[C:14](=[O:26])[C:13]=12)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
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참가 물질

6

반응물 3

HCID 6228DimethylformamideHCID 11776TriphenylphosphineHCID 68864116Ethyl 8-(benzyloxy)-6-bromo-2-(4-fluorobenzyl)-1-oxo-1,2,3,4-tetrahydropyrrolo[1,2-a]-pyrazine-7-carboxylate

생성물 1

HCID 68864512Ethyl 8-(benzyloxy)-6-cyano-2-(4-fluorobenzyl)-1-oxo-1,2,3,4-tetrahydropyrrolo[1,2-a]-pyrazine-7-carboxylate

시약·촉매·용매 2

HCID 11186
Zinc cyanide (Zn(CN)2)
촉매
HCID 9811564Bis(dibenzylideneacetone)palladium촉매

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온도
100 °C

실험 절차

A solution of ethyl 8-(benzyloxy)-6-bromo-2-(4-fluorobenzyl)-1-oxo-1,2,3,4-tetrahydropyrrolo[1,2-a]-pyrazine-7-carboxylate (1.40 g, 2.79 mmol; Example 1, Step 7), zinc cyanide (0.26 g, 2.23 mmol), tris(dibenzylideneacetone)dipalladium (0) (0.51 g, 0.56 mmol), triphenylphosphine (0.15 g, 0.56 mmol) in DMF (4.5 mL) was purged with nitrogen for 5 minutes. The reaction mixture was heated at 100° C. overnight and concentrated under vacuum. The reaction mixture was partitioned between dichloromethane and brine. The organic extract was dried over sodium sulfate, filtered and concentrated. The residue was subjected to column chromatography on silica gel eluted with 0-10% methanol in chloroform gradient to provide titled product.

후처리

  1. concentrationconcentrated under vacuum
  2. customThe reaction mixture was partitioned between dichloromethane and brine
  3. extractionThe organic extract
  4. dry with materialwas dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. washeluted with 0-10% methanol in chloroform gradient

출처 및 근거

ORD 기록
ord-fd3ea4ca3a4646e4b1c6b6078d159930
출처 데이터셋
uspto-grants-2009_05
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07538112B2

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