Potassium Phosphate, Tribasic → 4-(5-(1,5-Dimethyl-1H-pyrazol-3-ylamino)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-2-(1-oxo-6,7,8,9-tetrahydropyrido[3,4-b]indolizin-2(1H)-yl)nicotinaldehyde

HRID 592984ノート

反応式

HRID 592984 の反応式
Cl[C:2]1[C:7]([CH:8]=[O:9])=[C:6]([N:10]2[CH:22]=[CH:21][C:20]3[N:19]4[C:14]([CH2:15][CH2:16][CH2:17][CH2:18]4)=[CH:13][C:12]=3[C:11]2=[O:23])[N:5]=[CH:4][CH:3]=1.[CH3:24][N:25]1[C:29]([CH3:30])=[CH:28][C:27]([NH:31][C:32]2[C:33](=[O:48])[N:34]([CH3:47])[CH:35]=[C:36](B3OC(C)(C)C(C)(C)O3)[CH:37]=2)=[N:26]1.C([O-])(=O)C.[Na+].[O-]P([O-])([O-])=O.[K+].[K+].[K+]>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(#N)C>[CH3:24][N:25]1[C:29]([CH3:30])=[CH:28][C:27]([NH:31][C:32]2[C:33](=[O:48])[N:34]([CH3:47])[CH:35]=[C:36]([C:2]3[C:7]([CH:8]=[O:9])=[C:6]([N:10]4[CH:22]=[CH:21][C:20]5[N:19]6[C:14]([CH2:15][CH2:16][CH2:17][CH2:18]6)=[CH:13][C:12]=5[C:11]4=[O:23])[N:5]=[CH:4][CH:3]=3)[CH:37]=2)=[N:26]1

参加物

8

反応物 4

HCID 62657Potassium Phosphate, TribasicHCID 517045Sodium AcetateHCID 580441963-(1,5-Dimethyl-1H-pyrazol-3-ylamino)-1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2(1H)-oneHCID 866844674-Chloro-2-(1-oxo-6,7,8,9-tetrahydropyrido[3,4-b]indolizin-2(1H)-yl)nicotinaldehyde

生成物 1

HCID 866844694-(5-(1,5-Dimethyl-1H-pyrazol-3-ylamino)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-2-(1-oxo-6,7,8,9-tetrahydropyrido[3,4-b]indolizin-2(1H)-yl)nicotinaldehyde収率 19.1%

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

反応条件

温度
90 °C

実験手順

A 50-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with 4-chloro-2-(1-oxo-6,7,8,9-tetrahydropyrido[3,4-b]indolizin-2(1H)-yl)nicotinaldehyde 245a (130 mg, 0.39 mmol, 1.0 eq.), 3-(1,5-dimethyl-1H-pyrazol-3-ylamino)-1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2(1H)-one 218a (600 mg, 1.75 mmol, 4.0 eq.), Pd(dppf)Cl2 (32 mg, 0.040 mmol, 0.1 eq.), sodium acetate (64 mg, 0.78 mmol, 2.0 eq.), K3PO4 (165 mg, 0.78 mmol, 2.0 eq.), acetonitrile (15 mL), and water (1 mL). After three cycles of vacuum/argon flush, the mixture was heated at 90° C. 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 50:1 dichloromethane/ethanol to afford 246a (38 mg, 19%) as a yellow solid. MS-ESI: [M+H]+ 510.3.

後処理

  1. customA 50-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser
  2. customAfter three cycles of vacuum/argon flush
  3. temperatureIt was then cooled to room temperature
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. customthe resulting residue was purified by silica-gel column chromatography
  7. washeluting with 50:1 dichloromethane/ethanol

出典と根拠

ORDレコード
ord-aa24e02b0d594e229de595ac2dfa90aa
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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