Pyridine → (S)-cyclopropyl(2-methyl-5-phenoxy-6-(2H-1,2,3-triazol-2-yl)-3,4-dihydroquinolin-1(2H)-yl)methanone

HRID 1051704Notes

Reaction equation

HRID 1051704 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.[C:23]1(B(O)O)[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.N1C=CC=CC=1.C(N(CC)CC)C>C([O-])(=O)C.[Cu+2].C([O-])(=O)C.ClCCl>[CH:1]1([C:4]([N:6]2[C:15]3[C:10](=[C:11]([O:21][C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)[C:12]([N:16]4[N:17]=[CH:18][CH:19]=[N:20]4)=[CH:13][CH:14]=3)[CH2:9][CH2:8][C@@H:7]2[CH3:22])=[O:5])[CH2:2][CH2:3]1

Participants

7

Reactant 4

HCID 1049PyridineHCID 8471TriethylamineHCID 66827Phenylboronic AcidHCID 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 118076381(S)-cyclopropyl(2-methyl-5-phenoxy-6-(2H-1,2,3-triazol-2-yl)-3,4-dihydroquinolin-1(2H)-yl)methanone

Reagents, catalysts & solvents 2

HCID 8895Cupric acetateCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
40 °C

Procedure

A 50-mL round-bottom flask equipped with balloon of air was charged with (S)-cyclopropyl(5-hydroxy-2-methyl-6-(2H-1,2,3-triazol-2-yl)-3,4-dihydroquinolin-1(2H)-yl)methanone (0.150 g, 0.50 mmol), phenylboronic acid (0.185 g, 1.52 mmol), copper (II) acetate (0.228 g, 1.26 mmol), pyridine (0.12 mL, 1.49 mmol), triethyl amine (0.10 mL, 0.75 mmol), and dichloromethane (4 mL), and the resulting mixture stirred for 18 h at 40° C. The reaction mixture was cooled to room temperature and filtered, and the filtrate was concentrated under vacuum. The residue was purified via column chromatography on silica gel (eluting with 5% dichloromethane/methanol). The product was further purified by preparative-HPLC with the following conditions (Waters I): Column, SunFire Prep C18, 5 um, 19×100 mm; Mobile phase, water (0.05% ammonium bicarbonate) and acetonitrile (55% to 75% acetonitrile in 7 min, flow rate: 20 mL/min); Detector, UV 220&254 nm. This afforded (S)-cyclopropyl(2-methyl-5-phenoxy-6-(2H-1,2,3-triazol-2-yl)-3,4-dihydroquinolin-1(2H)-yl)methanone (0.025 g, 14%) as a white solid. 1H NMR (300 MHz, CD3OD) δ ppm 0.76-0.84 (m, 1H), 0.91-1.06 (m, 2H), 1.15-1.23 (m, 4H), 1.43-1.52 (m, 1H), 1.94-2.04 (m, 1H), 2.21-2.49 (m, 2H), 2.75-2.88 (m, 1H), 4.75-4.83 (m, 1H), 6.65-6.74 (m, 2H), 6.92 (d, J=7.20 Hz, 1H), 7.17 (t, J=7.50 Hz, 2H), 7.52 (d, J=8.70 Hz, 1H), 7.62 (d, J=8.70 Hz, 1H), 7.75 (s, 2H). MS (ESI, pos. ion) m/z 375 [M+H]+.

Workup

  1. customA 50-mL round-bottom flask equipped with balloon of air
  2. temperatureThe reaction mixture was cooled to room temperature
  3. filtrationfiltered
  4. concentrationthe filtrate was concentrated under vacuum
  5. customThe residue was purified via column chromatography on silica gel (eluting with 5% dichloromethane/methanol)
  6. customThe product was further purified by preparative-HPLC with the following conditions (Waters I)
  7. customMobile phase, water (0.05% ammonium bicarbonate) and acetonitrile (55% to 75% acetonitrile in 7 min, flow rate: 20 mL/min)

Sources & evidence

ORD record
ord-cad4d151f3784c2e98e63635d671cc80
Source dataset
uspto-grants-2016_07
Patent number
US09388161B2

Reaction notes

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