Potassium Phosphate, Tribasic → (4-(1-Methyl-5-(4-(1-methylazetidin-3-yl)phenylamino)-6-oxo-1,6-dihydro-pyridin-3-yl)-2-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)pyridin-3-yl)methyl Acetate

HRID 592965ノート

反応式

HRID 592965 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=2)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1.[C:22]([O:25][CH2:26][C:27]1[C:28]([N:42]2[CH2:54][CH2:53][N:45]3[C:46]4[CH2:47][CH2:48][CH2:49][CH2:50][C:51]=4[CH:52]=[C:44]3[C:43]2=[O:55])=[N:29][CH:30]=[CH:31][C:32]=1B1OC(C)(C)C(C)(C)O1)(=[O:24])[CH3:23].[O-]P([O-])([O-])=O.[K+].[K+].[K+].[C:64]([O-])(=O)C.[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].C(#N)C.O>[C:22]([O:25][CH2:26][C:27]1[C:28]([N:42]2[CH2:54][CH2:53][N:45]3[C:46]4[CH2:47][CH2:48][CH2:49][CH2:50][C:51]=4[CH:52]=[C:44]3[C:43]2=[O:55])=[N:29][CH:30]=[CH:31][C:32]=1[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:64]=[CH:13][C:14]([CH:17]3[CH2:20][N:19]([CH3:21])[CH2:18]3)=[CH:15][CH:16]=2)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1)(=[O:24])[CH3:23]

参加物

8

反応物 4

HCID 62657Potassium Phosphate, TribasicHCID 517045Sodium AcetateHCID 580440835-Bromo-1-methyl-3-(5-(1-methylazetidin-3-yl)pyridin-2-ylamino)pyridine-2(1H)-oneHCID 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 acetate

生成物 1

HCID 86684455(4-(1-Methyl-5-(4-(1-methylazetidin-3-yl)phenylamino)-6-oxo-1,6-dihydro-pyridin-3-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 54.9%

試薬・触媒・溶媒 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 962Water溶媒HCID 6342Acetonitrile溶媒

実験手順

A 50-mL round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with 239c (106 mg, 0.30 mmol), 3-(acetoxymethyl)-2-(1-oxo-3,4,6,7,8,9-hexa-hydropyrazino[1,2-a]indol-2(1H)-yl)pyridin-4-ylboronic acid 113i (115 mg, 0.30 mmol), Pd(dppf)Cl2 (25 mg, 0.030 mmol), K3PO4 (127 mg, 0.60 mmol), sodium acetate (49 mg, 0.60 mmol), water (1 mL) and acetonitrile (10 mL). After three cycles of vacuum/argon flush, the mixture was heated under reflux for 2 h. It was then cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure and the resulting residue was purified by silica-gel column chromatography eluting with 15:1 dichloromethane/methanol to afford 239d as white solid (100 mg, 49%). MS-ESI: [M+H]+ 607.3

後処理

  1. customA 50-mL round-bottomed flask equipped with a magnetic stirrer and a reflux condenser
  2. customAfter three cycles of vacuum/argon flush
  3. temperaturethe mixture was heated
  4. temperatureunder reflux for 2 h
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated under reduced pressure
  7. customthe resulting residue was purified by silica-gel column chromatography
  8. washeluting with 15:1 dichloromethane/methanol

出典と根拠

ORDレコード
ord-7fd575c35c134975ad57dadf06b06436
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…