Potassium Phosphate, Tribasic → 2-(6-tert-Butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-(1-methyl-5-(2-methylpyrimidin-4-ylamino)-6-oxo-1,6-dihydropyridin-3-yl)nicotinaldehyde

HRID 407646ノート

反応式

HRID 407646 の反応式
[CH3:1][N:2]1[CH:7]=[C:6](B2OC(C)(C)C(C)(C)O2)[CH:5]=[C:4]([NH:17][C:18]2[CH:23]=[CH:22][N:21]=[C:20]([CH3:24])[N:19]=2)[C:3]1=[O:25].[C:26]([C:30]1[CH:31]=[C:32]2[C:37](=[C:38]([F:40])[CH:39]=1)[C:36](=[O:41])[N:35]([C:42]1[N:49]=[CH:48][CH:47]=[C:46](Cl)[C:43]=1[CH:44]=[O:45])[N:34]=[CH:33]2)([CH3:29])([CH3:28])[CH3:27].[O-]P([O-])([O-])=O.[K+].[K+].[K+].C([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].O.C(#N)C>[C:26]([C:30]1[CH:31]=[C:32]2[C:37](=[C:38]([F:40])[CH:39]=1)[C:36](=[O:41])[N:35]([C:42]1[N:49]=[CH:48][CH:47]=[C:46]([C:6]3[CH:5]=[C:4]([NH:17][C:18]4[CH:23]=[CH:22][N:21]=[C:20]([CH3:24])[N:19]=4)[C:3](=[O:25])[N:2]([CH3:1])[CH:7]=3)[C:43]=1[CH:44]=[O:45])[N:34]=[CH:33]2)([CH3:29])([CH3:27])[CH3:28]

参加物

8

反応物 4

HCID 62657Potassium Phosphate, TribasicHCID 517045Sodium AcetateHCID 866839152-(6-tert-Butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-chloronicotinaldehydeHCID 866839351-Methyl-3-(2-methylpyrimidin-4-ylamino)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2(1H)-one

生成物 1

HCID 866839342-(6-tert-Butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-(1-methyl-5-(2-methylpyrimidin-4-ylamino)-6-oxo-1,6-dihydropyridin-3-yl)nicotinaldehyde収率 36%

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
100 °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 114b (236 mg, 0.69 mmol), 2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-chloronicotinaldehyde 103b (250 mg, 0.69 mmol), PdCl2(dppf) (29 mg, 0.035 mmol), K3PO4 (296 mg, 1.39 mmol), sodium acetate (114 mg, 1.39 mmol), acetonitrile (15 mL), and water (1 mL). The system was evacuated and refilled with N2. The reaction mixture was heated at 100° 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 30:1 dichloromethane/methanol to afford 114c (134 mg, 36%) as a yellow solid. MS-ESI: [M+H]+ 540.2.

後処理

  1. customA 50-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser
  2. customThe system was evacuated
  3. additionrefilled with N2
  4. temperatureIt was then cooled to room temperature
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated under reduced pressure
  7. customthe resulting residue was purified by silica-gel column chromatography
  8. washeluting with 30:1 dichloromethane/methanol

出典と根拠

ORDレコード
ord-068ddc0dea7246a59136c934c9dcffca
出典データセット
uspto-grants-2014_06
特許番号
US08754077B2

反応ノート

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