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1-[5-(2-Hydroxy-1,1-dimethyl-ethyl)-isoxazol-3-yl]-3-{4-[7-(2-morpholin-4-yl-ethoxy)-benzo[d]imidazo[2,1-b]thiazol-2-yl]-phenyl}-urea → 3,4,5-Triacetoxy-6-{2-methyl-2-[3-(3-{4-[7-(2-morpholin-4-yl-ethoxy)-benzo[d]imidazo[2,1-b]thiazol-2-yl]-phenyl}-ureido)-isoxazol-5-yl]-propoxy}-tetrahydro-pyran-2-carboxylic acid methyl ester

HRID 1038337
ノート
印刷プレビュー

反応式

HRID 1038337 の反応式
[OH:1][CH2:2][C:3]([C:6]1[O:10][N:9]=[C:8]([NH:11][C:12]([NH:14][C:15]2[CH:20]=[CH:19][C:18]([C:21]3[N:22]=[C:23]4[N:27]([CH:28]=3)[C:26]3[CH:29]=[CH:30][C:31]([O:33][CH2:34][CH2:35][N:36]5[CH2:41][CH2:40][O:39][CH2:38][CH2:37]5)=[CH:32][C:25]=3[S:24]4)=[CH:17][CH:16]=2)=[O:13])[CH:7]=1)([CH3:5])[CH3:4].[CH3:42][O:43][C:44](=[O:65])[C@H:45]1[O:51][C@:49](Br)(O)[C@H:48]([O:53][C:54](=[O:56])[CH3:55])[C@@H:47]([O:57][C:58](=[O:60])[CH3:59])[C@@H:46]1[O:61][C:62](=[O:64])[CH3:63]>C1(C)C=CC=CC=1.C(=O)([O-])[O-].[Ag+2]>[CH3:42][O:43][C:44]([CH:45]1[CH:46]([O:61][C:62](=[O:64])[CH3:63])[CH:47]([O:57][C:58](=[O:60])[CH3:59])[CH:48]([O:53][C:54](=[O:56])[CH3:55])[CH:49]([O:1][CH2:2][C:3]([CH3:4])([C:6]2[O:10][N:9]=[C:8]([NH:11][C:12]([NH:14][C:15]3[CH:20]=[CH:19][C:18]([C:21]4[N:22]=[C:23]5[N:27]([CH:28]=4)[C:26]4[CH:29]=[CH:30][C:31]([O:33][CH2:34][CH2:35][N:36]6[CH2:41][CH2:40][O:39][CH2:38][CH2:37]6)=[CH:32][C:25]=4[S:24]5)=[CH:17][CH:16]=3)=[O:13])[CH:7]=2)[CH3:5])[O:51]1)=[O:65]
参加物実験手順後処理出典と根拠反応ノート

参加物

5

反応物 2

HCID 461867861-[5-(2-Hydroxy-1,1-dimethyl-ethyl)-isoxazol-3-yl]-3-{4-[7-(2-morpholin-4-yl-ethoxy)-benzo[d]imidazo[2,1-b]thiazol-2-yl]-phenyl}-ureaHCID 54062351methyl 2,3,4-tri-O-acetyl-1-bromo-alpha-d-glucopyranuronate

生成物 1

HCID 667944213,4,5-Triacetoxy-6-{2-methyl-2-[3-(3-{4-[7-(2-morpholin-4-yl-ethoxy)-benzo[d]imidazo[2,1-b]thiazol-2-yl]-phenyl}-ureido)-isoxazol-5-yl]-propoxy}-tetrahydro-pyran-2-carboxylic acid methyl ester

試薬・触媒・溶媒 2

HCID 178418647
HCID 178418647、化合物
触媒
HCID 1140Toluene溶媒

実験手順

To a stirred mixture of 1-[5-(2-hydroxy-1,1-dimethyl-ethyl)-isoxazol-3-yl]-3-{4-[7-(2-morpholin-4-yl-ethoxy)-benzo[d]imidazo[2,1-b]thiazol-2-yl]-phenyl}-urea (I-1) (1 equivalent) and silver carbonate (0.5-1 equivalent) in toluene at rt is added 1-bromo-2,3,4-tri-O-acetyl-α-D-glucuronic acid methyl ester (0.8-1.5 equivalents) and the mixture is stirred at rt until the reaction is substantially complete as monitored by LCMS or TLC. The mixture is filtered and the filtrate is partitioned between water and either dichloromethane or a mixture of dichloromethane and isopropanol. The separated aqueous layer is further extracted with dichloromethane or a mixture of dichloromethane and isopropanol. The combined organic layers are washed with 2N aq sodium hydroxide dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The residue is purified by preparative reverse-phase HPLC or silica gel flash chromatography to afford 3,4,5-triacetoxy-6-{2-methyl-2-[3-(3-{4-[7-(2-morpholin-4-yl-ethoxy)-benzo[d]imidazo[2,1-b]thiazol-2-yl]-phenyl}-ureido)-isoxazol-5-yl]-propoxy}-tetrahydro-pyran-2-carboxylic acid methyl ester.

後処理

  1. filtrationThe mixture is filtered
  2. customthe filtrate is partitioned between water
  3. additioneither dichloromethane or a mixture of dichloromethane and isopropanol
  4. extractionThe separated aqueous layer is further extracted with dichloromethane
  5. additiona mixture of dichloromethane and isopropanol
  6. washThe combined organic layers are washed with 2N aq sodium hydroxide
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe residue is purified by preparative reverse-phase HPLC or silica gel flash chromatography

出典と根拠

ORDレコード
ord-119e13a3e6924d43980fed37563873c9
出典データセット
uspto-grants-2013_10
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08551963B2

反応ノート

読み込み中…

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