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 1185060노트

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HRID 1185060 반응식
[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]

참가 물질

8

반응물 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

생성물 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)nicotinaldehyde수율 36%

시약·촉매·용매 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 962Water용매HCID 6342Acetonitrile용매

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온도
100 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-bfecd49a32d647ee84489886acb73134
출처 데이터셋
uspto-grants-2014_03
특허 번호
US08669251B2

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