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 519111ノート

反応式

HRID 519111 の反応式
[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]

参加物

7

反応物 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

生成物 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 ester収率 58%

試薬・触媒・溶媒 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 702Ethanol溶媒HCID 962Water溶媒

反応条件

温度
100 °C

実験手順

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]+

後処理

  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)

出典と根拠

ORDレコード
ord-a08b8cc64889467cbf3e6f5576cdc704
出典データセット
uspto-grants-2015_08
特許番号
US09115151B2

反応ノート

読み込み中…