Water → (4-(1-Methyl-5-(5-(1-methylazetidin-3-yl)pyridin-2-ylamino)-6-oxo-1,6-dihydropyridin-3-yl)-2-(1-oxo-3,4,6,7,8,9-hexahydropyrido[3,4-b]indolizin-2(1H)-yl)pyridin-3-yl)methyl Acetate

HRID 592981ノート

反応式

HRID 592981 の反応式
Br[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:16]=[CH:15][C:14]([CH:17]3[CH2:20][N:19]([CH3:21])[CH2:18]3)=[CH:13][N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1.[C:22]([O:25][CH2:26][C:27]1[C:28]([N:36]2[CH2:48][CH2:47][C:46]3[N:45]4[C:40]([CH2:41][CH2:42][CH2:43][CH2:44]4)=[CH:39][C:38]=3[C:37]2=[O:49])=[N:29][CH:30]=[CH:31][C:32]=1B(O)O)(=[O:24])[CH3:23].[O-]P([O-])([O-])=O.[K+].[K+].[K+].O>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].C(#N)C>[C:22]([O:25][CH2:26][C:27]1[C:28]([N:36]2[CH2:48][CH2:47][C:46]3[N:45]4[C:40]([CH2:41][CH2:42][CH2:43][CH2:44]4)=[CH:39][C:38]=3[C:37]2=[O:49])=[N:29][CH:30]=[CH:31][C:32]=1[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:16]=[CH:15][C:14]([CH:17]3[CH2:20][N:19]([CH3:21])[CH2:18]3)=[CH:13][N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1)(=[O:24])[CH3:23]

参加物

7

反応物 4

HCID 962WaterHCID 62657Potassium Phosphate, TribasicHCID 580440835-Bromo-1-methyl-3-(5-(1-methylazetidin-3-yl)pyridin-2-ylamino)pyridine-2(1H)-oneHCID 866844643-(Acetoxymethyl)-2-(1-oxo-3,4,6,7,8,9-hexahydropyrido[3,4-b]indolizin-2(1H)-yl)pyridin-4-ylboronic Acid

生成物 1

HCID 86684465(4-(1-Methyl-5-(5-(1-methylazetidin-3-yl)pyridin-2-ylamino)-6-oxo-1,6-dihydropyridin-3-yl)-2-(1-oxo-3,4,6,7,8,9-hexahydropyrido[3,4-b]indolizin-2(1H)-yl)pyridin-3-yl)methyl Acetate収率 43%

試薬・触媒・溶媒 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 6342Acetonitrile溶媒

反応条件

温度
100 °C

実験手順

A 50-mL round-bottomed flask equipped with a reflux condenser was charged with 5-bromo-1-methyl-3-(5-(1-methylazetidin-3-yl)pyridin-2-ylamino)pyridin-2(1H)-one 239c (140 mg, 0.40 mmol), 244c (230 mg, 0.60 mmol), Pd(dppf)Cl2 (20 mg, 0.020 mmol), K3PO4 (180 mg, 0.80 mmol), sodium acetate•3 water (120 mg, 0.80 mmol), water (0.5 mL), and acetonitrile (10 mL). After three cycles of vacuum/argon flush, the mixture was heated at 100° C. for 2 h. It was then filtered and the filtrate was evaporated under reduced pressure. The residue was purified on silica-gel column chromatography eluting with 25:1 dichloromethane/methanol to afford 244d as a yellow solid (90 mg, 43%). MS-ESI: [M+H]+ 608.3

後処理

  1. customA 50-mL 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 under reduced pressure
  5. customThe residue was purified on silica-gel column chromatography
  6. washeluting with 25:1 dichloromethane/methanol

出典と根拠

ORDレコード
ord-ca12aa53b2e542fbb7a782b17ef513ca
出典データセット
uspto-grants-2016_01
特許番号
US09238655B2

反応ノート

読み込み中…