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

HRID 1185221Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1185221
Cl[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:23]=[C:14]3[CH2:15][N:16]([CH:19]4[CH2:22][O:21][CH2:20]4)[CH2:17][CH2:18][N:13]3[N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[N:7]=1.[C:24]([O:27][CH2:28][C:29]1[C:30]([N:44]2[N:53]=[CH:52][C:51]3[C:46](=[C:47]([F:58])[CH:48]=[C:49]([C:54]([CH3:57])([CH3:56])[CH3:55])[CH:50]=3)[C:45]2=[O:59])=[N:31][CH:32]=[CH:33][C:34]=1B1OC(C)(C)C(C)(C)O1)(=[O:26])[CH3:25].C1CCC(P(C2CCCCC2)C2CCCCC2)CC1.C([O-])([O-])=O.[Cs+].[Cs+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O.O1CCOCC1>[C:24]([O:27][CH2:28][C:29]1[C:30]([N:44]2[N:53]=[CH:52][C:51]3[C:46](=[C:47]([F:58])[CH:48]=[C:49]([C:54]([CH3:56])([CH3:55])[CH3:57])[CH:50]=3)[C:45]2=[O:59])=[N:31][CH:32]=[CH:33][C:34]=1[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:23]=[C:14]3[CH2:15][N:16]([CH:19]4[CH2:22][O:21][CH2:20]4)[CH2:17][CH2:18][N:13]3[N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[N:7]=1)(=[O:26])[CH3:25]

Komponenten

8

Edukt 4

HCID 10796Cesium carbonateHCID 75806TricyclohexylphosphineHCID 667422666-Chloro-2-methyl-4-(5-(oxetan-3-yl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-yl amino)pyridazin-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

Produkt 1

HCID 86684068(2-(6-tert-Butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-(1-methyl-5-(5-(oxetan-3-yl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)-6-oxo-1,6-dihydropyridazin-3-yl)pyridin-3-yl)methyl AcetateAusbeute 16,3 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 962WaterLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
110 °C

Versuchsvorschrift

A 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with 155c (367 mg, 1.1 mmol), 3-(acetoxymethyl)-2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)pyridine-4-ylboronic acid 116c (908.6 mg, 2.2 mmol), Pd2(dba)3 (100.6 mg, 0.11 mmol), P(cy)3 (122.8 mg, 0.44 mmol), Cs2CO3 (717 mg, 2.2 mmol), dioxane (20 mL), and water (0.5 mL). After three cycles of vacuum/argon flush, the mixture was heated at 110° C. for 2 h. It was then filtered and the filtrate was evaporated under reduced pressure. The residue was purified by silica-gel column chromatography eluting with 35:1 dichloromethane/methanol to afford 155d (120 mg, 16%) as a yellow solid. MS-ESI: [M+H]+ 669.8

Aufarbeitung

  1. customA 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and 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 by silica-gel column chromatography
  6. washeluting with 35:1 dichloromethane/methanol

Quellen und Nachweise

ORD-Eintrag
ord-26a6b29ec65346b9abcd8954e21835f7
Quelldatensatz
uspto-grants-2014_03
Patentnummer
US08669251B2

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