Water → (S)-8-((2-amino-4-methylpentyl)oxy)-9-hydroxy-6-methylbenzo[c][2,7]naphthyridin-5(6H)-one

HRID 1398301ノート

反応式

HRID 1398301 の反応式
Br[C:2]1[C:17]([O:18][CH2:19][C@@H:20]([NH:25]C(=O)OC(C)(C)C)[CH2:21][CH:22]([CH3:24])[CH3:23])=[CH:16][C:5]2[N:6]([CH3:15])[C:7](=[O:14])[C:8]3[C:13]([C:4]=2[CH:3]=1)=[CH:12][CH:11]=[N:10][CH:9]=3.CCCC[N+](CCCC)(CCCC)CCCC.[OH-].O.CC1C=CC2C(=C([OH:63])C=CC=2)N=1>CS(C)=O.[Cu]I>[NH2:25][C@@H:20]([CH2:21][CH:22]([CH3:23])[CH3:24])[CH2:19][O:18][C:17]1[C:2]([OH:63])=[CH:3][C:4]2[C:13]3[C:8](=[CH:9][N:10]=[CH:11][CH:12]=3)[C:7](=[O:14])[N:6]([CH3:15])[C:5]=2[CH:16]=1

参加物

7

反応物 4

HCID 962WaterHCID 132242-Methyl-8-hydroxyquinolineHCID 2723671Tetrabutylammonium HydroxideHCID 86710307(S)-tert-butyl (1-((9-bromo-6-methyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate

生成物 1

HCID 73213726(S)-8-((2-amino-4-methylpentyl)oxy)-9-hydroxy-6-methylbenzo[c][2,7]naphthyridin-5(6H)-one収率 55%

試薬・触媒・溶媒 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 679Dimethyl Sulfoxide溶媒

反応条件

温度
120 °C

実験手順

A mixture of (S)-tert-butyl (1-((9-bromo-6-methyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate (0.05 g, 0.099 mmol) (as prepared in Ex. 3, Part A), tetra-N-butylammonium hydroxide. 30H2O (0.463 g, 1.784 mmol) and water (1.5 mL) was added over 0.1 h to a stirred solution of copper(I) iodide (1.89 mg, 9.91 μmol) and 2-methyl 8-quinolinol (3.16 mg, 0.020 mmol) in DMSO (1 mL). The reaction mixture was heated to 120° C. and stirred for 14 h. The resulting mixture was cooled to room temperature. The crude product was purified by reverse phase HPLC (10 mM ammonium acetate) to afford a (S)-8-((2-amino-4-methylpentyl)oxy)-9-hydroxy-6-methylbenzo[c][2,7]naphthyridin-5(6H)-one (0.004 g, 0.011 mmol, 12% yield) as a brown solid. LC/MS (ESI) m/e 342.2 [(M+H)+, calcd for C19H24N3O3, 342.2]; HPLC retention time (method F): tR=1.62 min. HPLC retention time (method B): tR=5.88 min. 1H NMR (400 MHz, CD3OD) δ 9.39 (s, 1H), 8.62 (d, J=6.00 Hz, 1H), 7.96 (d, J=5.60 Hz, 1H), 7.56 (s, 1H), 6.73 (s, 1H), 3.80 (s, 3H), 3.67-3.70 (m, 1H), 3.49-3.59 (m, 2H), 1.81-1.85 (m, 1H), 1.56-1.63 (m, 2H), 1.05 (d, J=6.80 Hz, 3H), 0.98 (d, J=6.80 Hz, 3H).

後処理

  1. customas prepared in Ex
  2. temperatureThe resulting mixture was cooled to room temperature
  3. customThe crude product was purified by reverse phase HPLC (10 mM ammonium acetate)

出典と根拠

ORDレコード
ord-5bb5b92574054b2a93a18965e4b05959
出典データセット
uspto-grants-2014_12
特許番号
US08901305B2

反応ノート

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