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

반응식

HRID 1051715 반응식
[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

참가 물질

6

반응물 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

생성물 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

시약·촉매·용매 1

HCID 6342Acetonitrile용매

반응 조건

온도
85 °C

실험 절차

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]+.

후처리

  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)

출처 및 근거

ORD 기록
ord-c6b29c66100540ee88771188e6b8cbfb
출처 데이터셋
uspto-grants-2016_07
특허 번호
US09388161B2

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