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

HRID 2199887노트

반응식

HRID 2199887 반응식
[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

참가 물질

7

반응물 3

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

생성물 1

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

시약·촉매·용매 3

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)촉매HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 312751,4-Dioxane용매

실험 절차

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]+.

후처리

  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)

출처 및 근거

ORD 기록
ord-03e19b42c381455ebe3697e532b3ffc8
출처 데이터셋
uspto-grants-2016_06
특허 번호
US09359352B2

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