Sodium Carbonate → 4-[3-Fluoro-2-(4-methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-7-yl)-phenyl]-piperazine-1-carboxylic acid tert-butyl ester

HRID 519111Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 519111
[CH3:1][CH:2]1[N:15]2[C:6]([CH2:7][O:8][C:9]3[C:14]2=[CH:13][CH:12]=[C:11](B2OC(C)(C)C(C)(C)O2)[CH:10]=3)=[N:5][NH:4][C:3]1=[O:25].[C:26]([O:30][C:31]([N:33]1[CH2:38][CH2:37][N:36]([C:39]2[CH:44]=[CH:43][CH:42]=[C:41]([F:45])[C:40]=2Br)[CH2:35][CH2:34]1)=[O:32])([CH3:29])([CH3:28])[CH3:27].C(=O)([O-])[O-].[Na+].[Na+]>CCO.O.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]>[C:26]([O:30][C:31]([N:33]1[CH2:38][CH2:37][N:36]([C:39]2[CH:44]=[CH:43][CH:42]=[C:41]([F:45])[C:40]=2[C:11]2[CH:10]=[C:9]3[C:14]([N:15]4[C:6]([CH2:7][O:8]3)=[N:5][NH:4][C:3](=[O:25])[CH:2]4[CH3:1])=[CH:13][CH:12]=2)[CH2:35][CH2:34]1)=[O:32])([CH3:29])([CH3:27])[CH3:28]

Komponenten

7

Edukt 3

HCID 10340Sodium CarbonateHCID 867274894-(2-Bromo-3-fluoro-phenyl)-piperazine-1-carboxylic acid tert-butyl esterHCID 867274914-Methyl-7-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one

Produkt 1

HCID 867274904-[3-Fluoro-2-(4-methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-7-yl)-phenyl]-piperazine-1-carboxylic acid tert-butyl esterAusbeute 58 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 702EthanolLösungsmittelHCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

To a solution of 4-methyl-7-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one (Preparation #19, 0.057 g, 0.174 mmol), 4-(2-bromo-3-fluoro-phenyl)-piperazine-1-carboxylic acid tert-butyl ester (0.06 g, 0.174 mmol) and Pd(dppf)Cl2 (0.012 g, 0.017 mmol) in EtOH (4 mL) and water (1 mL) was added sodium carbonate (0.036 g, 0.34 mmol) and the reaction mixture was stirred at 100° C. for 4 h. The reaction mixture was cooled to ambient temperature and concentrated in vacuo. The residue was purified by column chromatography on silica gel (eluting with 30% EtOAc in petroleum ether) to give 4-[3-fluoro-2-(4-methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-7-yl)-phenyl]-piperazine-1-carboxylic acid tert-butyl ester (0.040 g, 58%). LC/MS (Table 1, Method 25) Rt=0.920 min; MS m/z: 496 [M+H]+

Aufarbeitung

  1. temperatureThe reaction mixture was cooled to ambient temperature
  2. concentrationconcentrated in vacuo
  3. customThe residue was purified by column chromatography on silica gel (eluting with 30% EtOAc in petroleum ether)

Quellen und Nachweise

ORD-Eintrag
ord-a08b8cc64889467cbf3e6f5576cdc704
Quelldatensatz
uspto-grants-2015_08
Patentnummer
US09115151B2

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