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 1473207Notes

Reaction equation

HRID 1473207 reaction equation
[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]

Participants

11

Reactant 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

Product 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 acidYield 177.8%

Reagents, catalysts & solvents 6

HCID 24463Copper sulfate pentahydrateCatalystHCID 54670067L-Ascorbic AcidCatalystHCID 702EthanolSolventHCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-e14f301053be4365b6962d4a309827ca
Source dataset
uspto-grants-2015_04
Patent number
US09012642B2

Reaction notes

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