Sodium Iodide → (S)-cyclopropyl(2-methyl-5-phenoxy-6-(4-(piperazin-1-yl)-1H-pyrazol-1-yl)-3,4-dihydroquinolin-1(2H)-yl)methanone

HRID 1051715

反応式

HRID 1051715 の反応式
[NH2:1][C:2]1[CH:3]=[N:4][N:5]([C:7]2[C:8]([O:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)=[C:9]3[C:14](=[CH:15][CH:16]=2)[N:13]([C:17]([CH:19]2[CH2:21][CH2:20]2)=[O:18])[C@@H:12]([CH3:22])[CH2:11][CH2:10]3)[CH:6]=1.Br[CH2:31][CH2:32][NH:33][CH2:34][CH2:35]Br.[I-].[Na+].C(=O)([O-])[O-].[Cs+].[Cs+]>C(#N)C>[CH:19]1([C:17]([N:13]2[C:14]3[C:9](=[C:8]([O:23][C:24]4[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=4)[C:7]([N:5]4[CH:6]=[C:2]([N:1]5[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]5)[CH:3]=[N:4]4)=[CH:16][CH:15]=3)[CH2:10][CH2:11][C@@H:12]2[CH3:22])=[O:18])[CH2:20][CH2:21]1

参加物

6

反応物 4

HCID 5238Sodium IodideHCID 10796Cesium carbonateHCID 415719Bis(2-bromoethyl)amineHCID 118075608(S)-(6-(4-amino-1H-pyrazol-1-yl)-2-methyl-5-phenoxy-3,4-dihydroquinolin-1(2H)-yl)(cyclopropyl)methanone

生成物 1

HCID 118075718(S)-cyclopropyl(2-methyl-5-phenoxy-6-(4-(piperazin-1-yl)-1H-pyrazol-1-yl)-3,4-dihydroquinolin-1(2H)-yl)methanone

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

反応条件

温度
85 °C

実験手順

A mixture of (S)-(6-(4-amino-1H-pyrazol-1-yl)-2-methyl-5-phenoxy-3,4-dihydroquinolin-1(2H)-yl)(cyclopropyl)methanone (0.020 g, 0.05 mmol), bis(2-bromoethyl)amine (0.020 g, 0.09 mmol), sodium iodide (0.003 g, 0.02 mmol), and cesium carbonate (0.084 g, 0.26 mmol) in acetonitrile (2 mL) stirred overnight at 85° C. The reaction mixture was cooled to room temperature and filtered. The filtrate was concentrated under vacuum, and the residue was purified by preparative thin layer chromatography (eluting with 10% methanol/dichloromethane). The product was further purified by preparative-HPLC with the following conditions: Column: XBridge RP C18, 19×150 mm, 5 um; Mobile Phase: water (0.05% ammonium bicarbonate) and acetonitrile (5% to 60% acetonitrile in 7.0 min, flow rate: 20 mL/min); Detector: UV220&254 nm. This afforded (5)-cyclopropyl(2-methyl-5-phenoxy-6-(4-(piperazin-1-yl)-1H-pyrazol-1-yl)-3,4-dihydroquinolin-1(2H)-yl)methanone (0.0011 g, 5%) as a light yellow solid. 1H NMR (300 MHz, CD3OD) δ ppm 0.96-0.82 (m, 1H), 0.91-1.06 (m, 2H), 1.15-1.22 (m, 3H), 1.31-1.38 (m, 2H), 1.42-1.51 (m, 1H), 1.95-2.07 (m, 1H), 2.21-2.32 (m, 1H), 2.33-2.45 (m, 1H), 2.73-2.92 (m, 9H), 4.55-4.65 (m, 1H), 6.71-6.79 (m, 2H), 6.93-7.01 (m, 1H), 7.19-7.26 (m, 2H), 7.40 (s, 1H), 7.45-7.50 (m, 1H), 7.54-7.63 (m, 2H). MS (ESI, pos. ion) m/z 458 [M+H]+.

後処理

  1. temperatureThe reaction mixture was cooled to room temperature
  2. filtrationfiltered
  3. concentrationThe filtrate was concentrated under vacuum
  4. customthe residue was purified by preparative thin layer chromatography (eluting with 10% methanol/dichloromethane)
  5. customThe product was further purified by preparative-HPLC with the following conditions
  6. customwater (0.05% ammonium bicarbonate) and acetonitrile (5% to 60% acetonitrile in 7.0 min, flow rate: 20 mL/min)

出典と根拠

ORDレコード
ord-c6b29c66100540ee88771188e6b8cbfb
出典データセット
uspto-grants-2016_07
特許番号
US09388161B2

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