Acetonitrile → 2-(6-tert-Butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-(1-methyl-5-(5-methyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)-6-oxo-1,6-dihydropyridazin-3-yl)nicotinaldehyde

HRID 1185214노트

반응식

HRID 1185214 반응식
[CH3:1][N:2]1[C:7](=[O:8])[C:6]([NH:9][C:10]2[CH:19]=[C:13]3[CH2:14][N:15]([CH3:18])[CH2:16][CH2:17][N:12]3[N:11]=2)=[CH:5][C:4](B(O)O)=[N:3]1.[C:23]([C:27]1[CH:28]=[C:29]2[C:34](=[C:35]([F:37])[CH:36]=1)[C:33](=[O:38])[N:32]([C:39]1[N:46]=[CH:45][CH:44]=[C:43](Cl)[C:40]=1[CH:41]=[O:42])C=[CH:30]2)([CH3:26])([CH3:25])[CH3:24].[O-]P([O-])([O-])=O.[K+].[K+].[K+].C([O-])(=O)C.[Na+].C(#[N:63])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:23]([C:27]1[CH:28]=[C:29]2[C:34](=[C:35]([F:37])[CH:36]=1)[C:33](=[O:38])[N:32]([C:39]1[N:46]=[CH:45][CH:44]=[C:43]([C:4]3[CH:5]=[C:6]([NH:9][C:10]4[CH:19]=[C:13]5[CH2:14][N:15]([CH3:18])[CH2:16][CH2:17][N:12]5[N:11]=4)[C:7](=[O:8])[N:2]([CH3:1])[N:3]=3)[C:40]=1[CH:41]=[O:42])[N:63]=[CH:30]2)([CH3:25])([CH3:26])[CH3:24]

참가 물질

8

반응물 5

HCID 6342AcetonitrileHCID 62657Potassium Phosphate, TribasicHCID 517045Sodium AcetateHCID 866840631-Methyl-5-(5-methyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)-6-oxo-1,6-dihydropyridazin-3-ylboronic AcidHCID 866840642-(6-tert-butyl-8-fluoro-1-oxoisoquinolin-2(1H)-yl)-4-chloronicotinaldehyde

생성물 1

HCID 866840622-(6-tert-Butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-(1-methyl-5-(5-methyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)-6-oxo-1,6-dihydropyridazin-3-yl)nicotinaldehyde수율 42%

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 25-mL round-bottomed flask equipped with a reflux condenser was charged with 153b (200 mg, 0.66 mmol), 2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-chloronicotinaldehyde 103b (240 mg, 0.66 mmol), PdCl2(dppf) (54 mg, 0.066 mmol), K3PO4 (250 mg, 1.2 mmol), sodium acetate (100 mg, 1.20 mmol), acetonitrile (10 mL), and water (0.5 mL). The system was evacuated and then refilled with N2. It was then heated at 100° C. for 1 h. The mixture was cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure and the residue was purified on silica-gel column eluting with 20:1 dichloromethane/methanol to afford 153c as a pale yellow solid (170 mg, 42%). MS-ESI: [M+H]+ 584.3.

후처리

  1. customA 25-mL round-bottomed flask equipped with a reflux condenser
  2. customThe system was evacuated
  3. additionrefilled with N2
  4. temperatureThe mixture was cooled to room temperature
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated under reduced pressure
  7. customthe residue was purified on silica-gel column
  8. washeluting with 20:1 dichloromethane/methanol

출처 및 근거

ORD 기록
ord-eee625840b2a44af9080e05ad0964bd5
출처 데이터셋
uspto-grants-2014_03
특허 번호
US08669251B2

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