Cesium carbonate → 1-(4-methoxybenzyl)-7-(3-hydroxyazetidin-1-yl)-1,5-naphthyridin-2(1H)-one

HRID 2199887ノート

反応式

HRID 2199887 の反応式
[CH3:1][O:2][C:3]1[CH:21]=[CH:20][C:6]([CH2:7][N:8]2[C:17]3[C:12](=[N:13][CH:14]=[C:15](Br)[CH:16]=3)[CH:11]=[CH:10][C:9]2=[O:19])=[CH:5][CH:4]=1.Cl.[NH:23]1[CH2:26][CH:25]([OH:27])[CH2:24]1.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>[CH3:1][O:2][C:3]1[CH:21]=[CH:20][C:6]([CH2:7][N:8]2[C:17]3[C:12](=[N:13][CH:14]=[C:15]([N:23]4[CH2:26][CH:25]([OH:27])[CH2:24]4)[CH:16]=3)[CH:11]=[CH:10][C:9]2=[O:19])=[CH:5][CH:4]=1

参加物

7

反応物 3

HCID 10796Cesium carbonateHCID 27592903-Hydroxyazetidine hydrochlorideHCID 679930111-(4-methoxybenzyl)-7-bromo-1,5-naphthyridin-2(1H)-one

生成物 1

HCID 679929881-(4-methoxybenzyl)-7-(3-hydroxyazetidin-1-yl)-1,5-naphthyridin-2(1H)-one収率 91%

試薬・触媒・溶媒 3

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)触媒HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 312751,4-Dioxane溶媒

実験手順

A mixture of 1-(4-methoxybenzyl)-7-bromo-1,5-naphthyridin-2(1H)-one (C-5) (8.1 g, 23.46 mmol, 1.0 eq), azetidin-3-ol hydrochloride (3.08 g, 28.15 mmol, 1.2 eq), Pd2(dba)3 (429 mg, 0.47 mmol, 0.02 eq), Xantphos (407 mg, 0.7 mmol, 0.03 eq) and Cs2CO3 (19.87 g, 61 mmol, 2.6 eq) in 1,4-dioxane (100 mL) was heated at reflux temperature under argon atmosphere overnight then cooled and filtered, the filter cake was washed with ethyl acetate and the combined filtrate was concentrated in vacuo and the residue was purified by column chromatography on silica gel (1-5% MeOH-DCM) to afford 1-(4-methoxybenzyl)-7-(3-hydroxyazetidin-1-yl)-1,5-naphthyridin-2(1H)-one (C-6) (7.2 g, 91% yield). 1H NMR (300 MHz, DMSO-d6) δ: 7.76 (m, 2H), 7.17 (d, J=8.7 Hz, 2H), 6.84 (d, J=8.7 Hz, 2H), 8.53 (m, 2H), 5.68 (d, J=6.3 Hz, 1H), 5.34 (s, 2H), 4.56 (m, 1H), 4.13 (m, 2H), 3.66 (s, 3H), 3.59 (m, 2H); ESI-MS m/z: 338.1 [M+H]+.

後処理

  1. temperaturewas heated
  2. temperatureat reflux temperature under argon atmosphere overnight
  3. temperaturethen cooled
  4. filtrationfiltered
  5. washthe filter cake was washed with ethyl acetate
  6. concentrationthe combined filtrate was concentrated in vacuo
  7. customthe residue was purified by column chromatography on silica gel (1-5% MeOH-DCM)

出典と根拠

ORDレコード
ord-03e19b42c381455ebe3697e532b3ffc8
出典データセット
uspto-grants-2016_06
特許番号
US09359352B2

反応ノート

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