Cesium carbonate → (S)-(5-cyclobutoxy-2-methyl-6-(2H-1,2,3-triazol-2-yl)-3,4-dihydroquinolin-1(2H)-yl)(cyclopropyl)methanone

HRID 1051703Notes

Reaction equation

HRID 1051703 reaction equation
[CH:1]1([C:4]([N:6]2[C:15]3[C:10](=[C:11]([OH:21])[C:12]([N:16]4[N:20]=[CH:19][CH:18]=[N:17]4)=[CH:13][CH:14]=3)[CH2:9][CH2:8][C@@H:7]2[CH3:22])=[O:5])[CH2:3][CH2:2]1.Br[CH:24]1[CH2:27][CH2:26][CH2:25]1.C(=O)([O-])[O-].[Cs+].[Cs+]>C(#N)C>[CH:24]1([O:21][C:11]2[C:12]([N:16]3[N:17]=[CH:18][CH:19]=[N:20]3)=[CH:13][CH:14]=[C:15]3[C:10]=2[CH2:9][CH2:8][C@H:7]([CH3:22])[N:6]3[C:4]([CH:1]2[CH2:2][CH2:3]2)=[O:5])[CH2:27][CH2:26][CH2:25]1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 78110BromocyclobutaneHCID 118076095(S)-cyclopropyl(5-hydroxy-2-methyl-6-(2H-1,2,3-triazol-2-yl)-3,4-dihydroquinolin-1(2H)-yl)methanone

Product 1

HCID 118076389(S)-(5-cyclobutoxy-2-methyl-6-(2H-1,2,3-triazol-2-yl)-3,4-dihydroquinolin-1(2H)-yl)(cyclopropyl)methanone

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of (S)-cyclopropyl(5-hydroxy-2-methyl-6-(2H-1,2,3-triazol-2-yl)-3,4-dihydroquinolin-1(2H)-yl)methanone (0.055 g, 0.18 mmol), bromocyclobutane (0.050 g, 0.37 mmol), and cesium carbonate (0.150 g, 0.46 mmol) in acetonitrile (5 mL) stirred for 18 h at 80° C. The reaction mixture was cooled to room temperature and filtered, and the filtrate was concentrated under vacuum. The residue was purified by preparative-HPLC with the following conditions (Waters 1): Column, XBridge Prep C18 OBD Column, 5 um, 19×150 mm; mobile phase, water (0.03% aqueous ammonia) and acetonitrile (16% to 34% acetonitrile in 10 min, flow rate: 20 mL/min); Detector: UV 220&254 nm. This afforded (S)-(5-cyclobutoxy-2-methyl-6-(2H-1,2,3-triazol-2-yl)-3,4-dihydroquinolin-1(2H)-yl)(cyclopropyl)methanone (0.030 g, 45%) as a white solid. 1H NMR (300 MHz, CD3OD) δ ppm 0.67-0.75 (m, 1H), 0.85-0.95 (m, 2H), 1.11-1.17 (m, 4H), 1.22-1.55 (m, 3H), 1.74-2.01 (m, 5H), 2.31-2.46 (m, 2H), 2.95-3.07 (m, 1H), 3.88-3.94 (m, 1H), 4.72-4.82 (m, 1H), 7.28 (d, J=8.40 Hz, 1H), 7.37 (d, J=8.40 Hz, 1H), 7.99 (s, 2H). MS (ESI, pos. ion) m/z 353 [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-HPLC with the following conditions (Waters 1)
  5. custommobile phase, water (0.03% aqueous ammonia) and acetonitrile (16% to 34% acetonitrile in 10 min, flow rate: 20 mL/min)

Sources & evidence

ORD record
ord-b4a11ad215324274a2342f1de5e75a61
Source dataset
uspto-grants-2016_07
Patent number
US09388161B2

Reaction notes

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