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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
ノート
印刷プレビュー

反応式

HRID 596131 の反応式
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
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

7

反応物 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

生成物 1

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

試薬・触媒・溶媒

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

反応条件

温度
90 °C

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-74aef9b90ff142f480baefeb02cc76b6
出典データセット
uspto-grants-2016_01
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09242996B2

反応ノート

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