Potassium Phosphate, Tribasic → 2-(6-tert-Butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-(5-(5-((2S,5R)-2,5-dimethyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-ylamino)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)nicotinaldehyde

HRID 407631ノート

反応式

HRID 407631 の反応式
[C:1]([C:5]1[CH:6]=[C:7]2[C:12](=[C:13]([F:15])[CH:14]=1)[C:11](=[O:16])[N:10]([C:17]1[N:24]=[CH:23][CH:22]=[C:21](Cl)[C:18]=1[CH:19]=[O:20])[N:9]=[CH:8]2)([CH3:4])([CH3:3])[CH3:2].[CH3:26][C@H:27]1[CH2:32][N:31]([CH:33]2[CH2:36][O:35][CH2:34]2)[C@H:30]([CH3:37])[CH2:29][N:28]1[C:38]1[CH:39]=[CH:40][C:41]([NH:44][C:45]2[C:46](=[O:60])[N:47]([CH3:59])[CH:48]=[C:49](B3OC(C)(C)C(C)O3)[CH:50]=2)=[N:42][CH:43]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CC#N.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:1]([C:5]1[CH:6]=[C:7]2[C:12](=[C:13]([F:15])[CH:14]=1)[C:11](=[O:16])[N:10]([C:17]1[N:24]=[CH:23][CH:22]=[C:21]([C:49]3[CH:50]=[C:45]([NH:44][C:41]4[CH:40]=[CH:39][C:38]([N:28]5[CH2:29][C@@H:30]([CH3:37])[N:31]([CH:33]6[CH2:36][O:35][CH2:34]6)[CH2:32][C@@H:27]5[CH3:26])=[CH:43][N:42]=4)[C:46](=[O:60])[N:47]([CH3:59])[CH:48]=3)[C:18]=1[CH:19]=[O:20])[N:9]=[CH:8]2)([CH3:4])([CH3:3])[CH3:2]

参加物

6

反応物 3

HCID 62657Potassium Phosphate, TribasicHCID 866839152-(6-tert-Butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-chloronicotinaldehydeHCID 866839293-(5-((2S,5R)-2,5-dimethyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-ylamino)-1-methyl-5-(4,4,5-trimethyl-1,3,2-dioxaborolan-2-yl)pyridin-2(1H)-one

生成物 1

HCID 866839282-(6-tert-Butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-(5-(5-((2S,5R)-2,5-dimethyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-ylamino)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)nicotinaldehyde収率 42%

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 100-mL single-neck round-bottomed flask was charged with 2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-chloronicotinaldehyde 103b (216 mg, 0.6 mmol), 3-(5-((2S,5R)-2,5-dimethyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-ylamino)-1-methyl-5-(4,4,5-trimethyl-1,3,2-dioxaborolan-2-yl)pyridin-2(1H)-one (360 mg, 0.72 mmol), Pd(dppf)Cl2 (30 mg, 0.03 mmol), K3PO4 (270 mg, 1.2 mmol), and NaOAc.3H2O (180 mg, 1.2 mmol) in CH3CN (80 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 flash column chromatography eluting with 25:1 of CH2Cl2/MeOH to afford 110a (160 mg, 42%) as a yellow brown solid. MS: [M+H]+ 693.3.

後処理

  1. customThe system was evacuated
  2. additionrefilled with N2
  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 flash column chromatography
  7. washeluting with 25:1 of CH2Cl2/MeOH

出典と根拠

ORDレコード
ord-6392635571db48de927933f8e5cb97d9
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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