Acetonitrile → (4-(4-Methyl-6-(6-(4-(oxetan-3-yl)piperazin-1-yl)pyridin-3-ylamino)-5-oxo-4,5-dihydropyrazin-2-yl)-2-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)pyridin-3-yl)methyl Acetate

HRID 1411775ノート

反応式

HRID 1411775 の反応式
Br[C:2]1[N:3]=[C:4]([NH:10][C:11]2[CH:12]=[N:13][C:14]([N:17]3[CH2:22][CH2:21][N:20]([CH:23]4[CH2:26][O:25][CH2:24]4)[CH2:19][CH2:18]3)=[CH:15][CH:16]=2)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1.[C:27]([O:30][CH2:31][C:32]1[C:33]([N:47]2[CH2:59][CH2:58][N:50]3[C:51]4[CH2:52][CH2:53][CH2:54][CH2:55][C:56]=4[CH:57]=[C:49]3[C:48]2=[O:60])=[N:34][CH:35]=[CH:36][C:37]=1B1OC(C)(C)C(C)(C)O1)(=[O:29])[CH3:28].C([O-])(=O)C.[Na+].C(#N)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>[C:27]([O:30][CH2:31][C:32]1[C:33]([N:47]2[CH2:59][CH2:58][N:50]3[C:51]4[CH2:52][CH2:53][CH2:54][CH2:55][C:56]=4[CH:57]=[C:49]3[C:48]2=[O:60])=[N:34][CH:35]=[CH:36][C:37]=1[C:2]1[N:3]=[C:4]([NH:10][C:11]2[CH:12]=[N:13][C:14]([N:17]3[CH2:22][CH2:21][N:20]([CH:23]4[CH2:26][O:25][CH2:24]4)[CH2:19][CH2:18]3)=[CH:15][CH:16]=2)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1)(=[O:29])[CH3:28]

参加物

7

反応物 4

HCID 6342AcetonitrileHCID 517045Sodium AcetateHCID 86684143(2-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)methyl acetateHCID 866843655-Bromo-1-methyl-3-(6-(4-(oxetan-3-yl)piperazin-1-yl)pyridin-3-ylamino)pyrazin-2(1H)-one

生成物 1

HCID 86684366(4-(4-Methyl-6-(6-(4-(oxetan-3-yl)piperazin-1-yl)pyridin-3-ylamino)-5-oxo-4,5-dihydropyrazin-2-yl)-2-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)pyridin-3-yl)methyl Acetate収率 70.5%

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
80 °C

実験手順

A round-bottomed flask equipped with a reflux condenser was charged with 197e (200 mg, 0.48 mmol), 3-(acetoxymethyl)-2-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)pyridin-4-ylboronic acid 113i (364 mg, 0.95 mmol), PdCl2(dppf) (40 mg, 0.049 mmol), K3PO43H2O (250 mg, 0.95 mmol), sodium acetate (80 mg, 0.95 mmol), acetonitrile (10 mL), and water (0.5 mL). After three cycles of vacuum/argon flush, the mixture was heated at 80° C. for 3 h. It was then filtered and the filtrate was evaporated in vacuo. The residue was purified by silica-gel column chromatography eluting with 1:20 methanol/dichloromethane to afford 197f as a red solid (230 mg, 70%). MS-ESI: [M+H]+ 680

後処理

  1. customA round-bottomed flask equipped with a reflux condenser
  2. customAfter three cycles of vacuum/argon flush
  3. filtrationIt was then filtered
  4. customthe filtrate was evaporated in vacuo
  5. customThe residue was purified by silica-gel column chromatography
  6. washeluting with 1:20 methanol/dichloromethane

出典と根拠

ORDレコード
ord-1375119d186b405f9a461950d42d6d63
出典データセット
uspto-grants-2014_12
特許番号
US08921353B2

反応ノート

読み込み中…