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Cesium carbonate → (S)-2-((1-acetyl-2-methyl-6-(1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)-1,2,3,4-tetrahydroquinolin-5-yl)oxy)benzonitrile

HRID 1051629
ノート
印刷プレビュー

反応式

HRID 1051629 の反応式
[C:1]([N:4]1[C:13]2[C:8](=[C:9]([O:15][C:16]3[CH:23]=[CH:22][CH:21]=[CH:20][C:17]=3[C:18]#[N:19])[C:10](Br)=[CH:11][CH:12]=2)[CH2:7][CH2:6][C@@H:5]1[CH3:24])(=[O:3])[CH3:2].[CH3:25][N:26]1[CH2:31][CH2:30][CH:29]([N:32]2[CH:36]=[C:35](B3OC(C)(C)C(C)(C)O3)[CH:34]=[N:33]2)[CH2:28][CH2:27]1.C(=O)([O-])[O-].[Cs+].[Cs+]>CC(C1C=C(C(C)C)C(C2C=CC=C(P(C3CCCCC3)C3CCCCC3)C=2)=C(C(C)C)C=1)C.C1C=[C-]C(C2C(N)=CC=CC=2)=CC=1.Cl[Pd+].O1CCOCC1.O>[C:1]([N:4]1[C:13]2[C:8](=[C:9]([O:15][C:16]3[CH:23]=[CH:22][CH:21]=[CH:20][C:17]=3[C:18]#[N:19])[C:10]([C:35]3[CH:34]=[N:33][N:32]([CH:29]4[CH2:30][CH2:31][N:26]([CH3:25])[CH2:27][CH2:28]4)[CH:36]=3)=[CH:11][CH:12]=2)[CH2:7][CH2:6][C@@H:5]1[CH3:24])(=[O:3])[CH3:2]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

7

反応物 3

HCID 10796Cesium carbonateHCID 59231689(1-(1-Methylpiperidin-4-yl)-1H-pyrazol-4-yl)boronic acid pinacol esterHCID 118075789(S)-2-((l-acetyl-6-bromo-2-methyl-1,2,3,4-tetrahydroquinolin-5-yl)oxy)benzonitrile

生成物 1

HCID 118075612(S)-2-((1-acetyl-2-methyl-6-(1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)-1,2,3,4-tetrahydroquinolin-5-yl)oxy)benzonitrile

試薬・触媒・溶媒 3

HCID 72376365
[2-(2-Aminophenyl)phenyl]-chloro-palladium dicyclohexyl-[3-(2,4,6-triisopropylphenyl)phenyl]phosphane
触媒
HCID 962Water溶媒
HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

A mixture of (S)-2-((l-acetyl-6-bromo-2-methyl-1,2,3,4-tetrahydroquinolin-5-yl)oxy)benzonitrile (0.017 g, 0.044 mmol), 1-methyl-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)piperidine (0.030 g, 0.101 mmol), XPhos Precatalyst 2nd Generation (3.47 mg, 4.41 μmol), and cesium carbonate (0.058 g, 0.177 mmol) in dioxane (2.0 mL) and water (0.400 mL) was heated at 100° C. for 16 h. The reaction mixture was filtered through Celite and concentrated to afford an orange oil. This material was purified via column chromatography on silica gel (Biotage 25 g column, gradient elution with 0-50% (90:10:1, dichloromethane/methanol/ammonium hydroxide)-dichloromethane) to afford (S)-2-(1-acetyl-2-methyl-6-(1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)-1,2,3,4-tetrahydroquinolin-5-yl)oxy)benzonitrile (0.017 g, 82%) as a white solid. 1H NMR (300 MHz, DMSO-d6) δ ppm 1.04 (d, J=7.04 Hz, 3H), 1.27-1.58 (m, 2H), 1.77-1.97 (m, 4H), 1.97-2.14 (m, 4H), 2.17 (s, 3H), 2.19 (s, 3H), 2.81 (br d, J=11.43 Hz, 2H), 3.90-4.17 (m, 1H), 4.62 (br s, 1H), 6.48 (br s, 1H), 7.14 (t, J=7.62 Hz, 1H), 7.39-7.56 (m, 2H), 7.61 (d, J=8.50 Hz, 1H), 7.72 (s, 1H), 7.89 (dd, J=7.77, 1.61 Hz, 1H), 8.01 (s, 1H). MS (ESI, pos. ion) m/z 470 [M+H]

後処理

  1. filtrationThe reaction mixture was filtered through Celite
  2. concentrationconcentrated
  3. customto afford an orange oil
  4. customThis material was purified via column chromatography on silica gel (Biotage 25 g column, gradient elution with 0-50% (90:10:1, dichloromethane/methanol/ammonium hydroxide)-dichloromethane)
  5. customto afford (S)-2-(1-acetyl-2-methyl-6-(1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)-1,2,3,4-tetrahydroquinolin-5-yl)oxy)benzonitrile (0.017 g, 82%) as a white solid

出典と根拠

ORDレコード
ord-7440448a4d9f40168c7e0fc91a597c46
出典データセット
uspto-grants-2016_07
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09388161B2

反応ノート

読み込み中…

このページの内容参加物反応条件実験手順後処理出典と根拠反応ノート