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Dichloromethane → Methyl 4-(3-amino-6-(1-(4-methoxybenzyl)-6-oxo-1,4,5,6-tetrahydropyridin-3-yl)pyrazin-2-yl)-2-fluorobenzoate

HRID 596131
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HRID 596131 반응식
I[C:2]1[CH2:3][CH2:4][C:5](=[O:17])[N:6]([CH2:8][C:9]2[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[CH:11][CH:10]=2)[CH:7]=1.C(Cl)Cl.[NH2:21][C:22]1[C:23]([C:29]2[CH:38]=[CH:37][C:32]([C:33]([O:35][CH3:36])=[O:34])=[C:31]([F:39])[CH:30]=2)=[N:24][C:25](Br)=[CH:26][N:27]=1.C([O-])([O-])=O.[Na+].[Na+]>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.Cl[Pd]Cl.[Fe+2].COCCOC>[NH2:21][C:22]1[C:23]([C:29]2[CH:38]=[CH:37][C:32]([C:33]([O:35][CH3:36])=[O:34])=[C:31]([F:39])[CH:30]=2)=[N:24][C:25]([C:2]2[CH2:3][CH2:4][C:5](=[O:17])[N:6]([CH2:8][C:9]3[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[CH:11][CH:10]=3)[CH:7]=2)=[CH:26][N:27]=1
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참가 물질

7

반응물 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 1180459305-iodo-1-(4-methoxybenzyl)-3,4-dihydropyridin-2(1H)-oneHCID 118046172Methyl 4-(3-amino-6-bromopyrazin-2-yl)-2-fluorobenzoate

생성물 1

HCID 118045295Methyl 4-(3-amino-6-(1-(4-methoxybenzyl)-6-oxo-1,4,5,6-tetrahydropyridin-3-yl)pyrazin-2-yl)-2-fluorobenzoate수율 42.5%

시약·촉매·용매 2

HCID 44119782Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 80711,2-Dimethoxyethane용매

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온도
90 °C

실험 절차

5-iodo-1-(4-methoxybenzyl)-3,4-dihydropyridin-2(1H)-one (630 mg, 1.836 mmol), PdCl2(dppf).CH2Cl2 adduct (150 mg, 0.184 mmol), methyl 4-(3-amino-6-bromopyrazin-2-yl)-2-fluorobenzoate (1028 mg, 2.75 mmol) and Na2CO3 (2754 μl, 5.51 mmol) were combined in a flask and then DME (Volume: 6120 μl) was added. The mixture was degassed and purged with nitrogen and then finally heated at 90° C. for 2 h upon which complete consumption of starting material was observed. The reaction mixture was diluted with EtOAc and water and the organic layer was separated and dried (MgSO4), filtered and concentrated in vacuo and the residue purified by flash chromatography (0-60% EtOAc/DCM) to afford 361 mg of the desired product as a yellow solid. LCMS (m/z): (MH+), 463.1, 0.88 min.

후처리

  1. customThe mixture was degassed
  2. custompurged with nitrogen
  3. additionThe reaction mixture was diluted with EtOAc and water
  4. customthe organic layer was separated
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customthe residue purified by flash chromatography (0-60% EtOAc/DCM)

출처 및 근거

ORD 기록
ord-74aef9b90ff142f480baefeb02cc76b6
출처 데이터셋
uspto-grants-2016_01
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09242996B2

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