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4-Methyl-6-(oxiran-2-yl)pyridine-3-carbonitrile → 6-(1-hydroxy-2-{4-[(2R)-2-hydroxy-2-(4-methyl-1-oxo-1,3-dihydro-2-benzofuran-5-yl)ethyl]piperazin-1-yl}ethyl)-4-methylpyridine-3-carbonitrile

HRID 1187151
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HRID 1187151 반응식
[CH3:1][C:2]1[CH:7]=[C:6]([CH:8]2[CH2:10][O:9]2)[N:5]=[CH:4][C:3]=1[C:11]#[N:12].[OH:13][C@H:14]([C:22]1[CH:31]=[CH:30][C:25]2[C:26](=[O:29])[O:27][CH2:28][C:24]=2[C:23]=1[CH3:32])[CH2:15][N:16]1[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]1>CCO>[OH:9][CH:8]([C:6]1[N:5]=[CH:4][C:3]([C:11]#[N:12])=[C:2]([CH3:1])[CH:7]=1)[CH2:10][N:19]1[CH2:20][CH2:21][N:16]([CH2:15][C@H:14]([OH:13])[C:22]2[CH:31]=[CH:30][C:25]3[C:26](=[O:29])[O:27][CH2:28][C:24]=3[C:23]=2[CH3:32])[CH2:17][CH2:18]1
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참가 물질

4

반응물 2

HCID 595686574-Methyl-6-(oxiran-2-yl)pyridine-3-carbonitrileHCID 595687285-[(1R)-1-hydroxy-2-piperazin-1-ylethyl]-4-methyl-2-benzofuran-1(3H)-one

생성물 1

HCID 498022206-(1-hydroxy-2-{4-[(2R)-2-hydroxy-2-(4-methyl-1-oxo-1,3-dihydro-2-benzofuran-5-yl)ethyl]piperazin-1-yl}ethyl)-4-methylpyridine-3-carbonitrile

시약·촉매·용매 1

HCID 702Ethanol용매

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온도
140 °C

실험 절차

To a microwave tube were added 4-methyl-6-(oxiran-2-yl)pyridine-3-carbonitrile (40 mg, 0.25 mmol), 5-[(1R)-1-hydroxy-2-(piperazin-1-yl)ethyl]-4-methyl-2-benzofuran-1(3H)-one (69 mg, 0.25 mmol, as a free base), and EtOH (3.0 mL). The mixture was heated in the microwave for 60 min at 140° C. The solvent was evaporated and the crude product was purified by chiral prep SFC (30% MeOH (0.1% DEA)/CO2 on OJ column) to provide 6-(1-hydroxy-2-{4-[(2R)-2-hydroxy-2-(4-methyl-1-oxo-1,3-dihydro-2-benzofuran-5-yl)ethyl]piperazin-1-yl}ethyl)-4-methylpyridine-3-carbonitrile as individual isomers. Further, the products were treated with 1 M HCl in diethyl ether to give the final products as HCl salts.

후처리

  1. customThe solvent was evaporated
  2. customthe crude product was purified by chiral prep SFC (30% MeOH (0.1% DEA)/CO2 on OJ column)

출처 및 근거

ORD 기록
ord-5e5211dc1fe24f0185d4c673f68e5ecf
출처 데이터셋
uspto-grants-2014_03
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08673920B2

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