Potassium Phosphate, Tribasic → (S)-2-(5-(5-(2-Ethyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-ylamino)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-4-fluoro-6-(1-oxo-6,7,8,9-tetrahydropyrazino[1,2-a]indol-2(1H)-yl)benzaldehyde

HRID 1843246

Reaktionsgleichung

Reaktionsgleichung von HRID 1843246
Br[C:2]1[CH:9]=[C:8]([F:10])[CH:7]=[C:6]([N:11]2[CH:23]=[CH:22][N:14]3[C:15]4[CH2:16][CH2:17][CH2:18][CH2:19][C:20]=4[CH:21]=[C:13]3[C:12]2=[O:24])[C:3]=1[CH:4]=[O:5].[CH2:25]([C@H:27]1[CH2:32][N:31]([CH:33]2[CH2:36][O:35][CH2:34]2)[CH2:30][CH2:29][N:28]1[C:37]1[CH:38]=[CH:39][C:40]([NH:43][C:44]2[C:45](=[O:60])[N:46]([CH3:59])[CH:47]=[C:48](B3OC(C)(C)C(C)(C)O3)[CH:49]=2)=[N:41][CH:42]=1)[CH3:26].[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>[CH2:25]([C@H:27]1[CH2:32][N:31]([CH:33]2[CH2:34][O:35][CH2:36]2)[CH2:30][CH2:29][N:28]1[C:37]1[CH:38]=[CH:39][C:40]([NH:43][C:44]2[C:45](=[O:60])[N:46]([CH3:59])[CH:47]=[C:48]([C:2]3[CH:9]=[C:8]([F:10])[CH:7]=[C:6]([N:11]4[CH:23]=[CH:22][N:14]5[C:15]6[CH2:16][CH2:17][CH2:18][CH2:19][C:20]=6[CH:21]=[C:13]5[C:12]4=[O:24])[C:3]=3[CH:4]=[O:5])[CH:49]=2)=[N:41][CH:42]=1)[CH3:26]

Komponenten

8

Edukt 4

HCID 62657Potassium Phosphate, TribasicHCID 517045Sodium AcetateHCID 86683743(S)-3-(5-(2-Ethyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-ylamino)-1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2(1H)-oneHCID 866837562-Bromo-4-fluoro-6-(1-oxo-6,7,8,9-tetrahydropyrazino[1,2-a]indol-2(1H)-yl)benzaldehyde

Produkt 1

HCID 86683758(S)-2-(5-(5-(2-Ethyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-ylamino)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-4-fluoro-6-(1-oxo-6,7,8,9-tetrahydropyrazino[1,2-a]indol-2(1H)-yl)benzaldehydeAusbeute 43,2 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 962WaterLösungsmittelHCID 6342AcetonitrileLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

A round-bottomed flask was charged with 2-bromo-4-fluoro-6-(1-oxo-6,7,8,9-tetrahydropyrazino[1,2-a]indol-2(1H)-yl)benzaldehyde 121f (159 mg, 0.41 mmol), 122a (213 mg, 0.43 mmol), PdCl2(dppf) (29 mg, 0.04 mmol), K3PO4 (182 mg, 0.86 mmol), sodium acetate (71 mg, 0.86 mmol), acetonitrile (15 mL), and water (1.5 mL). After three cycles of vacuum/argon flush, the mixture was heated at 80° C. for 3 h. It was then filtered and the filtrate was evaporated under reduced pressure. The residue was purified by silica-gel column chromatography eluting with 1:20 methanol/dichloromethane to afford 122b as a red solid (120 mg, 43%). MS: [M+H]+ 678.3

Aufarbeitung

  1. customAfter three cycles of vacuum/argon flush
  2. filtrationIt was then filtered
  3. customthe filtrate was evaporated under reduced pressure
  4. customThe residue was purified by silica-gel column chromatography
  5. washeluting with 1:20 methanol/dichloromethane

Quellen und Nachweise

ORD-Eintrag
ord-f263f573092d4037adf41f67943a7a12
Quelldatensatz
uspto-grants-2015_02
Patentnummer
US08946213B2

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