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Hydrochloric Acid → 2-Tert-butoxy-2-[4-(4-chlorophenyl)-1-[[1-(2-hydroxyethyl)triazol-4-yl]methyl]-6-methyl-7-oxo-pyrrolo[2,3-c]pyridin-5-yl]acetic acid

HRID 1473207
ノート
印刷プレビュー

反応式

HRID 1473207 の反応式
[C:1]([O:5][CH:6]([C:11]1[N:16]([CH3:17])[C:15](=[O:18])[C:14]2[N:19]([CH2:22][C:23]#[CH:24])[CH:20]=[CH:21][C:13]=2[C:12]=1[C:25]1[CH:30]=[CH:29][C:28]([Cl:31])=[CH:27][CH:26]=1)[C:7]([O:9]C)=[O:8])([CH3:4])([CH3:3])[CH3:2].C([O:35][CH2:36][CH2:37][N:38]=[N+:39]=[N-:40])(=O)C.[Li+].[OH-].Cl>C(O)C.O.CO.O1CCCC1.O.O.O.O.O.S([O-])([O-])(=O)=O.[Cu+2].O=C1O[C@H]([C@H](CO)O)C(O)=C1O>[C:1]([O:5][CH:6]([C:11]1[N:16]([CH3:17])[C:15](=[O:18])[C:14]2[N:19]([CH2:22][C:23]3[N:40]=[N:39][N:38]([CH2:37][CH2:36][OH:35])[CH:24]=3)[CH:20]=[CH:21][C:13]=2[C:12]=1[C:25]1[CH:26]=[CH:27][C:28]([Cl:31])=[CH:29][CH:30]=1)[C:7]([OH:9])=[O:8])([CH3:4])([CH3:2])[CH3:3]
参加物実験手順後処理出典と根拠反応ノート

参加物

11

反応物 4

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 120185192-Azidoethyl acetateHCID 89462668methyl 2-(tert-butoxy)-2-(4-(4-chlorophenyl)-6-methyl-7-oxo-1-(prop-2-yn-1-yl)-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-5-yl)acetate

生成物 1

HCID 715384792-Tert-butoxy-2-[4-(4-chlorophenyl)-1-[[1-(2-hydroxyethyl)triazol-4-yl]methyl]-6-methyl-7-oxo-pyrrolo[2,3-c]pyridin-5-yl]acetic acid
収率 177.8%

試薬・触媒・溶媒 6

HCID 24463Copper sulfate pentahydrate触媒HCID 54670067L-Ascorbic Acid触媒HCID 702Ethanol溶媒HCID 887Methanol溶媒HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

A suspension of methyl 2-(tert-butoxy)-2-(4-(4-chlorophenyl)-6-methyl-7-oxo-1-(prop-2-yn-1-yl)-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-5-yl)acetate (20 mg, 0.045 mmol), 2-azidoethyl acetate (8.53 μL, 0.074 mmol), copper(II) sulfate pentahydrate (1.240 mg, 4.96 μmol) and L-(+)-ascorbic acid (0.874 mg, 4.96 μmol) in Ethanol (1.000 mL) and Water (0.2 mL) was irradiated in the microwave at 120° C. for 20 minutes. The mixture was diluted with Methanol (1.000 mL), and Tetrahydrofuran (THF) (1.000 mL), treated with 2M LiOH (1 mL, 2.000 mmol) and then stirred at ambient temperature overnight. The mixture was treated with 1M HCl until pH<2, extracted with ethyl acetate, concentrated and purified by reverse phase chromatography (10-90% MeCN/H2O-0.1% TFA, 12 min) to afford 2-(tert-butoxy)-2-(4-(4-chlorophenyl)-1-((1-(2-hydroxyethyl)-1H-1,2,3-triazol-4-yl)methyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-5-yl)acetic acid (4.3 mg, 0.08 mmol, 7% yield) as a white solid. 1H NMR (400 MHz, CHLOROFORM-d) ppm 7.88-7.83 (m, 1H), 7.62-7.56 (m, 1H), 7.50-7.44 (m, 2H), 7.41-7.36 (m, 1H), 7.34-7.31 (m, 1H), 7.23-7.20 (m, 1H), 6.07-5.99 (m, 1H), 5.99-5.94 (m, 1H), 5.78-5.69 (m, 1H), 5.37-5.32 (s, 1H), 4.49-4.43 (m, 2H), 4.09-4.04 (m, 2H), 3.67 (s, 3H), 1.02 (s, 9H); LCMS (m/z) ES+=514 (M+1).

後処理

  1. customwas irradiated in the microwave at 120° C. for 20 minutes
  2. extractionextracted with ethyl acetate
  3. concentrationconcentrated
  4. custompurified by reverse phase chromatography (10-90% MeCN/H2O-0.1% TFA, 12 min)

出典と根拠

ORDレコード
ord-e14f301053be4365b6962d4a309827ca
出典データセット
uspto-grants-2015_04
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09012642B2

反応ノート

読み込み中…

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