Sodium Iodide → 3-(2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyloxy)-4-[(4-{3-[1-(2-hydroxyethylcarbamoyl)-1-(methyl)ethylamino]propoxy}phenyl)methyl]-5-isopropyl-1H-pyrazole

HRID 1869001노트

반응식

HRID 1869001 반응식
[C:1]([O:4][C@@H:5]1[C@@H:10]([O:11][C:12](=[O:14])[CH3:13])[C@H:9]([O:15][C:16](=[O:18])[CH3:17])[C@@H:8]([CH2:19][O:20][C:21](=[O:23])[CH3:22])[O:7][C@H:6]1[O:24][C:25]1[C:29]([CH2:30][C:31]2[CH:36]=[CH:35][C:34]([O:37][CH2:38][CH2:39][CH2:40]OS(C)(=O)=O)=[CH:33][CH:32]=2)=[C:28]([CH:46]([CH3:48])[CH3:47])[NH:27][N:26]=1)(=[O:3])[CH3:2].[NH2:49][C:50]([CH3:58])([CH3:57])[C:51]([NH:53][CH2:54][CH2:55][OH:56])=[O:52].[I-].[Na+]>C(#N)C.C(O)C>[C:1]([O:4][C@@H:5]1[C@@H:10]([O:11][C:12](=[O:14])[CH3:13])[C@H:19]([O:20][C:21](=[O:23])[CH3:22])[C@@H:8]([CH2:9][O:15][C:16](=[O:18])[CH3:17])[O:7][C@H:6]1[O:24][C:25]1[C:29]([CH2:30][C:31]2[CH:36]=[CH:35][C:34]([O:37][CH2:38][CH2:39][CH2:40][NH:49][C:50]([C:51](=[O:52])[NH:53][CH2:54][CH2:55][OH:56])([CH3:58])[CH3:57])=[CH:33][CH:32]=2)=[C:28]([CH:46]([CH3:47])[CH3:48])[NH:27][N:26]=1)(=[O:3])[CH3:2]

참가 물질

6

반응물 3

HCID 5238Sodium IodideHCID 216527992-(2-Amino-2-methylpropionylamino)ethanolHCID 866020253-(2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyloxy)-5-isopropyl-4-({4-[3-(methanesulfonyloxy)-propoxy]phenyl}methyl)-1H-pyrazole

생성물 1

HCID 689458553-(2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyloxy)-4-[(4-{3-[1-(2-hydroxyethylcarbamoyl)-1-(methyl)ethylamino]propoxy}phenyl)methyl]-5-isopropyl-1H-pyrazole수율 60.7%

시약·촉매·용매 2

HCID 702Ethanol용매HCID 6342Acetonitrile용매

실험 절차

To a solution of 3-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyloxy)-4-{[4-(3-hydroxypropoxy)phenyl]methyl}-5-isopropyl-1H-pyrazole (0.77 g) in dichloromethane (5 mL) were added triethylamine (0.26 mL) and methanesulfonyl chloride (0.12 mL), and the mixture was stirred at room temperature for 30 minutes. The reaction mixture was poured into 0.5 mol/L hydrochloric acid, and the resulting mixture was extracted with ethyl acetate. The organic layer was washed with water and brine, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure to give 3-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyloxy)-5-isopropyl-4-({4-[3-(methanesulfonyloxy)-propoxy]phenyl}methyl)-1H-pyrazole (0.85 g). The obtained 3-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyloxy)-5-isopropyl-4-({4-[3-(methanesulfonyloxy)propoxy]phenyl}-methyl)-1H-pyrazole (0.2 g) was dissolved in a mixed solvent of acetonitrile (1.5 mL) and ethanol (1.5 mL). To the solution were added 2-[2-amino-2-(methyl)propionylamino]ethanol (0.25 g) and a catalytic amount of sodium iodide, and the mixture was stirred at 60° C. for 4 days. The reaction mixture was concentrated under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: dichloromethane/methanol=20/1-10/1) to give 3-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyloxy)-4-[(4-{3-[1-(2-hydroxyethylcarbamoyl)-1-(methyl)ethylamino]propoxy}phenyl)methyl]-5-isopropyl-1H-pyrazole (0.13 g). This material was dissolved in methanol (3 mL). To the solution was added sodium methoxide (28% methanol solution, 0.05 mL), and the mixture was stirred at room temperature for 3 hours. The reaction mixture was concentrated under reduced pressure, and the residue was purified by solid phase extraction on ODS (washing solvent: distilled water, eluent: methanol) to give the title compound (93 mg).

후처리

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. customthe residue was purified by column chromatography on silica gel (eluent: dichloromethane/methanol=20/1-10/1)

출처 및 근거

ORD 기록
ord-bb048cda888c4253b433b051d93560b5
출처 데이터셋
uspto-grants-2009_12
특허 번호
US07635684B2

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