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 519111Notes

Reaction equation

HRID 519111 reaction equation
[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]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 86727489HCID 86727489, compoundHCID 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

Product 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 esterYield 58%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

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]+

Workup

  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)

Sources & evidence

ORD record
ord-a08b8cc64889467cbf3e6f5576cdc704
Source dataset
uspto-grants-2015_08
Patent number
US09115151B2

Reaction notes

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