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

HRID 1051704ノート

反応式

HRID 1051704 の反応式
[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

参加物

7

反応物 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

生成物 1

HCID 118076381(S)-cyclopropyl(2-methyl-5-phenoxy-6-(2H-1,2,3-triazol-2-yl)-3,4-dihydroquinolin-1(2H)-yl)methanone

試薬・触媒・溶媒 2

HCID 8895Cupric acetate触媒HCID 6344Dichloromethane溶媒

反応条件

温度
40 °C

実験手順

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]+.

後処理

  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)

出典と根拠

ORDレコード
ord-cad4d151f3784c2e98e63635d671cc80
出典データセット
uspto-grants-2016_07
特許番号
US09388161B2

反応ノート

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