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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
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HRID 1473207 반응식
[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]
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참가 물질

11

반응물 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

생성물 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
수율 177.8%

시약·촉매·용매 6

HCID 24463Copper sulfate pentahydrate촉매HCID 54670067L-Ascorbic Acid촉매HCID 702Ethanol용매HCID 887Methanol용매HCID 962Water용매HCID 8028Tetrahydrofuran용매

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-e14f301053be4365b6962d4a309827ca
출처 데이터셋
uspto-grants-2015_04
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09012642B2

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