1,2-Dimethoxyethane → 6-(4-(1H-imidazol-2-yl)-2-methoxyphenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine

HRID 1027293

反応式

HRID 1027293 の反応式
[CH3:1][O:2][C:3]1[CH:8]=[C:7](B2OC(C)(C)C(C)(C)O2)[CH:6]=[CH:5][C:4]=1[C:18]1[N:23]=[N:22][C:21]([N:24]([CH3:35])[CH:25]2[CH2:30][C:29]([CH3:32])([CH3:31])[NH:28][C:27]([CH3:34])([CH3:33])[CH2:26]2)=[CH:20][CH:19]=1.Br[C:37]1[NH:38][CH:39]=[CH:40][N:41]=1.C([O-])([O-])=O.[Na+].[Na+].COCCOC>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O.CCO>[NH:41]1[CH:40]=[CH:39][N:38]=[C:37]1[C:7]1[CH:6]=[CH:5][C:4]([C:18]2[N:23]=[N:22][C:21]([N:24]([CH3:35])[CH:25]3[CH2:26][C:27]([CH3:33])([CH3:34])[NH:28][C:29]([CH3:31])([CH3:32])[CH2:30]3)=[CH:20][CH:19]=2)=[C:3]([O:2][CH3:1])[CH:8]=1

参加物

8

反応物 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 27732612-Bromo-1H-imidazoleHCID 867107236-(2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine2 回

生成物 1

HCID 867107226-(4-(1H-imidazol-2-yl)-2-methoxyphenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine収率 45.3%

試薬・触媒・溶媒 3

HCID 178418476HCID 178418476、化合物触媒HCID 702Ethanol溶媒HCID 962Water溶媒

反応条件

温度
150 °C

実験手順

To a microwave vial was added 6-(2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine (Intermediate 9-3, 100 mg, 0.21 mmol), 2-bromo-1H-imidazole (61.2 mg, 0.42 mmol), Na2CO3 (44 mg, 0.42 mmol), and Pd(PPh3)2Cl2 (14 mg, 0.02 mmol), followed by DME (1 mL)/EtOH 0.25 mL)/(H2O (0.25 mL). The vial was purged with N2 for 10 min and the reaction mixture was heated at 150° C. in a microwave reactor for 20 min. The reaction mixture was filtered through celite and the filter cake was washed with EtOAc. The filtrate was concentrated in vacuo to give the crude product which was purified by silica gel chromotography (5%-15% MeOH/DCM) to afford 6-(4-(1H-imidazol-2-yl)-2-methoxyphenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine (40 mg, MS: 421.3 [M+H+]).

後処理

  1. customThe vial was purged with N2 for 10 min
  2. filtrationThe reaction mixture was filtered through celite
  3. washthe filter cake was washed with EtOAc
  4. concentrationThe filtrate was concentrated in vacuo
  5. customto give the crude product which
  6. customwas purified by silica gel chromotography (5%-15% MeOH/DCM)

出典と根拠

ORDレコード
ord-547d5d0c91494a3eba24cf62eb4b2e9b
出典データセット
uspto-grants-2014_05
特許番号
US08729263B2

関連ノート

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