Dimethylformamide → 2-(10-Fluoro-1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)-4-(4-methyl-5-oxo-6-(pyridin-3-ylamino)-4,5-dihydropyrazin-2-yl)nicotinaldehyde

HRID 592777ノート

反応式

HRID 592777 の反応式
[CH3:1][N:2]1[C:7](=[O:8])[C:6]([NH:9][C:10]2[CH:11]=[N:12][CH:13]=[CH:14][CH:15]=2)=[N:5][C:4](B(O)O)=[CH:3]1.Cl[C:20]1[C:25]([CH:26]=[O:27])=[C:24]([N:28]2[CH2:41][CH2:40][N:31]3[C:32]4[CH2:33][CH2:34][CH2:35][CH2:36][C:37]=4[C:38]([F:39])=[C:30]3[C:29]2=[O:42])[N:23]=[CH:22][CH:21]=1.C([O-])([O-])=O.[Na+].[Na+].CN(C=O)C>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].O>[F:39][C:38]1[C:37]2[CH2:36][CH2:35][CH2:34][CH2:33][C:32]=2[N:31]2[CH2:40][CH2:41][N:28]([C:24]3[N:23]=[CH:22][CH:21]=[C:20]([C:4]4[N:5]=[C:6]([NH:9][C:10]5[CH:11]=[N:12][CH:13]=[CH:14][CH:15]=5)[C:7](=[O:8])[N:2]([CH3:1])[CH:3]=4)[C:25]=3[CH:26]=[O:27])[C:29](=[O:42])[C:30]=12

参加物

7

反応物 4

HCID 6228DimethylformamideHCID 10340Sodium CarbonateHCID 866842384-Chloro-2-(10-fluoro-1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)nicotinaldehydeHCID 866843344-Methyl-5-oxo-6-(pyridin-3-ylamino)-4,5-dihydropyrazin-2-ylboronic acid

生成物 1

HCID 866843352-(10-Fluoro-1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)-4-(4-methyl-5-oxo-6-(pyridin-3-ylamino)-4,5-dihydropyrazin-2-yl)nicotinaldehyde収率 49.4%

試薬・触媒・溶媒 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 962Water溶媒

反応条件

温度
50 °C

実験手順

A 50-mL round-bottomed flask equipped with a reflux condenser was charged with 186b (127 mg, 0.52 mmol), 4-chloro-2-(10-fluoro-1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)nicotinaldehyde 134c (180 mg, 0.52 mmol), Na2CO3 (110 mg, 1.04 mmol), PdCl2(dppf) (38 mg, 0.052 mmol), DMF (12 mL), and water (1 mL). After bubbling nitrogen through the mixture for 30 minutes, it was heated at 50° C. for 8 hours under nitrogen. The reaction was then cooled to room temperature and concentrated under reduce pressure. The residue was purified by silica-gel column chromatography eluting with 30:1 methylene chloride/methanol to afford 186c (132 mg, 49%) as a brown solid. MS-ESI: [M+H]+ 514.3.

後処理

  1. customA 50-mL round-bottomed flask equipped with a reflux condenser
  2. customAfter bubbling nitrogen through the mixture for 30 minutes
  3. temperatureThe reaction was then cooled to room temperature
  4. concentrationconcentrated
  5. customThe residue was purified by silica-gel column chromatography
  6. washeluting with 30:1 methylene chloride/methanol

出典と根拠

ORDレコード
ord-9088d6064c9c44ad9cf3ebf258e0ea36
出典データセット
uspto-grants-2016_01
特許番号
US09238655B2

反応ノート

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