Acetonitrile → 2-(6-tert-Butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-(1-methyl-6-oxo-5-(pyrimidin-4-ylamino)-1,6-dihydropyridin-3-yl)nicotinaldehyde

HRID 407643노트

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HRID 407643 반응식
[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][N:27]1[CH:32]=[C:31](B2OC(C)(C)C(C)(C)O2)[CH:30]=[C:29]([NH:42][C:43]2[CH:48]=[CH:47][N:46]=[CH:45][N:44]=2)[C:28]1=[O:49].[O-]P([O-])([O-])=O.[K+].[K+].[K+].C(#N)C>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: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:31]3[CH:30]=[C:29]([NH:42][C:43]4[CH:48]=[CH:47][N:46]=[CH:45][N:44]=4)[C:28](=[O:49])[N:27]([CH3:26])[CH:32]=3)[C:18]=1[CH:19]=[O:20])[N:9]=[CH:8]2)([CH3:4])([CH3:3])[CH3:2]

참가 물질

7

반응물 4

HCID 6342AcetonitrileHCID 62657Potassium Phosphate, TribasicHCID 580438621-methyl-3-(pyrimidin-4-ylamino)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2(1H)-oneHCID 866839152-(6-tert-Butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-chloronicotinaldehyde

생성물 1

HCID 866839322-(6-tert-Butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-(1-methyl-6-oxo-5-(pyrimidin-4-ylamino)-1,6-dihydropyridin-3-yl)nicotinaldehyde수율 51%

시약·촉매·용매 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 962Water용매

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온도
100 °C

실험 절차

A 100-mL round-bottomed flask equipped with a reflux condenser was charged with 2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-chloronicotinaldehyde 103b (110 mg, 0.31 mmol), 113b (100 mg, 0.31 mmol), PdCl2(dppf) (25 mg, 0.030 mmol), K3PO4 (241 mg, 0.93 mmol), NaAcO (76 mg, 0.93 mmol), acetonitrile (15 mL), and water (0.5 mL). After three cycles of vacuum/argon flush, the mixture was heated at 100° C. for 3 h. It was then filtered and the filtrate was evaporated under reduced pressure. The residue was purified with silica-gel column chromatography eluting with 1:20 methanol/dichloromethane to afford 113c as a red solid (80 mg, 51%). MS-ESI: [M+H]+ 526.3

후처리

  1. customA 100-mL round-bottomed flask equipped with a reflux condenser
  2. customAfter three cycles of vacuum/argon flush
  3. filtrationIt was then filtered
  4. customthe filtrate was evaporated under reduced pressure
  5. customThe residue was purified with silica-gel column chromatography
  6. washeluting with 1:20 methanol/dichloromethane

출처 및 근거

ORD 기록
ord-e990f8078f4545c6a696ec8c6e499e47
출처 데이터셋
uspto-grants-2014_06
특허 번호
US08754077B2

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