Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Process for preparing 6-o-alkenyl-substituted erythromycin derivatives

A technology of erythromycin derivatives, 6-O-, applied in the field of preparation of 6-O-substituted erythromycin derivatives

Inactive Publication Date: 2002-11-13
ABBVIE INC
View PDF19 Cites 3 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, there are no known reports of palladium-catalyzed substitution, derivatization or selective allylation of hydroxyl groups of erythromycin derivatives

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0123] Preparation of 6-O-allyl-2',4"-O-di-trimethyl from allyl tert-butyl carbonate

[0124] Silylerythromycin A-9-(O-isopropoxy-cyclohexyl ketal) oxime

[0125] (Compound (III), Reaction Scheme 1) Step (1): 2', 4 "-two-trimethylsilyl erythromycin A-9-(O-isopropoxycyclohexyl ketal) oxime preparation

[0126] The above compound was prepared according to the method described in US Patent 4,990,602. Step (2): 6-O-allyl-2', 4"-O-bis-trimethylsilyl erythromycin A-9-(O-isopropoxycyclohexyl ketal) oxime preparation

[0127] 2', 4"-O-bis(trimethylsilyl)erythromycin A 9-(O-isopropoxycyclohexyl ketal) oxime) (30.0g, 29.0mmol, 1 equivalent), ene Propyl tert-butyl carbonate (6.65 g, 1.45 equiv), palladium acetate (33 mg, 0.005 equiv), triphenylphosphine (330 mg, 0.043 equiv) and 150 mL of THF were added to a suitable reaction vessel. The reaction mixture was pumped After being vacuumed and purged several times with nitrogen, it was heated to reflux for 19 hour...

Embodiment 2

[0131] Preparation of 6-O-allyl 2',4"-di-O- from allyl isopropyl carbonate

[0132] Trimethylsilyl-erythromycin A 9-(O-isopropoxycyclohexyl ketal) oxime

[0133] The title compound was prepared according to the method of Example 1 step (2) with a crude product yield of 80%, except that 1.8 molar equivalents of allyl isopropyl carbonate prepared in Reference Example 4 were used instead of allyl tertiary Butyl carbonate.

Embodiment 3

[0135] 6-O-[3-(3-quinolinyl)-2-propen-1-yl]-2',4"-di-O-trimethylsilyl-

[0136] Preparation of erythromycin A 9-(O-isopropoxycyclohexyl ketal) oxime

[0137] The title compound was prepared according to the method of Example 1 step (2) with a crude product yield of 92%, except that 1.2 molar equivalents of 1-(3-quinolyl)-2-propene prepared in Reference Example 5 were used -1-ol tert-butyl carbonate instead of allyl tert-butyl carbonate.

[0138] 1 H NMR (400MHz, CDCl 3 ): 9.06 (clear doublet, 1H), 8.30 (clear doublet, 1H), 8.04 (clear doublet, 1H), 7.78 (clear doublet, 1H), 7.61 (clear doublet, doublet peak, 1H), 7.48 (obvious double doublet, 1H), 6.62-6.50 (m, 2H), 5.19 (clear doublet, 1H), 4.80 (obvious doublet, 1H), 4.56-4.39 (m, 2H), 4.28-4.24(m, 2H), 4.13-4.01(m, 2H), 3.83-3.65(m, 5H), 3.30-3.15(m, 6H), 2.91-2.82(m, 1H) , 2.75-2.70(m, 1H), 2.65-2.51(m, 1H), 2.35-2.20(m, 7H), 2.10-1.02(m, 50H), 0.89-0.82(m, 4H), 0.16(s, 9H), 0.12(s, 9H). 13 CNMR (100MHz, CDCl...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

In one aspect, the present invention relates to a method for preparing 6-O-substituted erythromycin derivatives, comprising converting 2′-substituted and optionally 4″-substituted 9- in the presence of a palladium catalyst and a phosphine. An oxime erythromycin derivative is reacted with an alkylating agent. In another aspect, the present invention relates to a method for preparing 6-O-substituted erythromycin ketolactone using a palladium-catalyzed alkylation reaction.

Description

[0001] This application claims priority from US Provisional Application No. 60 / 140,968, filed June 24,1999. technical field [0002] The present invention relates to a method for preparing 6-O-substituted erythromycin derivatives and 6-O-substituted erythromycin ketolides thereof. In particular, the present invention relates to the preparation of 6-O-substituted erythromycin derivatives from erythromycins using alkylating agents in the presence of phosphines, and their subsequent conversion to 6-O-substituted erythromycin ketones A palladium-catalyzed approach to yl lactones. Background of the invention [0003] 6-O-Methylerythromycin A (clathromycin) is a potent macrolide antibiotic disclosed in U.S. Patent 4,331,803. [0004] The method for preparing clarithromycin is generally a four-step method using erythromycin A as a raw material: step 1: optionally converting the 9-oxo group into an oxime; step 2: protecting 2' and 4" hydroxyl...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
IPC IPC(8): A61P31/04C07B61/00C07H1/00C07H17/08
CPCC07H17/08A61P31/04C07H1/00
Inventor E·J·斯托纳M·J·彼得森顾宜音R·D·钦克A·J·科珀M·N·德斯潘德T·格里梅A·R·海特D·R·希尔玛格丽特·季萍·徐S·A·金M·R·莱恩纳E·C·李M·A·麦劳林H·E·莫尔顿J·J·纳皮尔D·J·普拉塔P·S·拉杰M·拉斯穆森D·里利健-和J·田S·J·维滕伯格
Owner ABBVIE INC
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com