Potassium Phosphate, Tribasic → (2-(6-tert-Butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-(5-(1,5-dimethyl-1H-pyrazol-3-ylamino)-1-methyl-6-oxo-1,6-dihydropyridazin-3-yl)pyridin-3-yl)methyl Acetate

HRID 1185113

反応式

HRID 1185113 の反応式
Cl[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:15]=[C:14]([CH3:16])[N:13]([CH3:17])[N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[N:7]=1.[C:18]([O:21][CH2:22][C:23]1[C:24]([N:38]2[N:47]=[CH:46][C:45]3[C:40](=[C:41]([F:52])[CH:42]=[C:43]([C:48]([CH3:51])([CH3:50])[CH3:49])[CH:44]=3)[C:39]2=[O:53])=[N:25][CH:26]=[CH:27][C:28]=1B1OC(C)(C)C(C)(C)O1)(=[O:20])[CH3:19].[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:18]([O:21][CH2:22][C:23]1[C:24]([N:38]2[N:47]=[CH:46][C:45]3[C:40](=[C:41]([F:52])[CH:42]=[C:43]([C:48]([CH3:50])([CH3:49])[CH3:51])[CH:44]=3)[C:39]2=[O:53])=[N:25][CH:26]=[CH:27][C:28]=1[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:15]=[C:14]([CH3:16])[N:13]([CH3:17])[N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[N:7]=1)(=[O:20])[CH3:19]

参加物

8

反応物 4

HCID 62657Potassium Phosphate, TribasicHCID 517045Sodium AcetateHCID 585400026-chloro-4-(1,5-dimethyl-1H-pyrazol-3-ylamino)-2-methylpyridazin-3(2H)-oneHCID 86683972(2-(6-tert-butyl-8-fluoro-1-oxophthalazin-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 86683974(2-(6-tert-Butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-(5-(1,5-dimethyl-1H-pyrazol-3-ylamino)-1-methyl-6-oxo-1,6-dihydropyridazin-3-yl)pyridin-3-yl)methyl Acetate収率 65.3%

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 127b (120 mg, 0.47 mmol), (2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)methyl acetate 116c (536 mg, 1.3 mmol), Pd(dppf)Cl2 (34 mg, 0.047 mmol), K3PO4 (199 mg, 0.94 mmol), sodium acetate (77 mg, 0.94 mmol), acetonitrile (10 mL), and water (0.2 mL). After three cycles of vacuum/argon flush, the 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 dichloromethane/methanol (100:1 to 30:1) to afford 127c (180 mg, 65%) as a black oil. MS-ESI: [M+H]+ 587.1

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 dichloromethane/methanol (100:1 to 30:1)

出典と根拠

ORDレコード
ord-8f14f58ee6e642c88adca0829249ed9b
出典データセット
uspto-grants-2014_03
特許番号
US08669251B2

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