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 1051715Notes

Reaction equation

HRID 1051715 reaction equation
[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

Participants

6

Reactant 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

Product 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

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
85 °C

Procedure

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]+.

Workup

  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)

Sources & evidence

ORD record
ord-c6b29c66100540ee88771188e6b8cbfb
Source dataset
uspto-grants-2016_07
Patent number
US09388161B2

Reaction notes

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