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

Method for preparing Darunavir intermediate

A technology of Chinese formula and compound, applied in the field of preparation of AIDS drug darunavir intermediate, which can solve the problems of high raw material cost and poor atom economy

Active Publication Date: 2017-11-14
成都博腾药业有限公司
View PDF5 Cites 3 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0024] But this synthetic method atom economy is poor, owing to need to use the higher periodic acid and lithium borohydride of price, cause the raw material cost of product higher

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

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Method for preparing Darunavir intermediate
  • Method for preparing Darunavir intermediate
  • Method for preparing Darunavir intermediate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0046] Under nitrogen protection, add 270 mL of 1.6 mol / L n-butyl lithium n-hexane solution to a 500 mL flask, cool to -78°C, and add 34.4 g (2.0 eq) 1,4-butyrolactone dropwise. After the dripping is completed, heat and stir for 2 hours, and then drip 31.2g (1.0eq, 0.2mol) 1,4-dioxaspiro[4,5]dec-2-one (compound of formula IV) in tetrahydrofuran. After the reaction was kept for 16 hours, the reaction was quenched with saturated ammonium chloride solution, the temperature was raised to room temperature, the layers were separated, the aqueous phase was extracted with ethyl acetate, the organic phases were combined, and the product was concentrated after concentration, with a yield of 38%.

[0047] 1 H NMR (CD 3 OD, 400MHz):δ4.64 (s, 2H), 3.72(t, J=6.3Hz, 2H), 2.42(t, J=6.3Hz, 2H)

[0048] 13 C NMR(CD 3 OD, 400MHz): δ178.77, 177.02, 98.39, 68.48, 61.21, 26.00

[0049] HRMS: M-1=143.0352

[0050] Melting point: 115-117°C.

Embodiment 2

[0052] Under the protection of nitrogen, add 160mL of 2.0mol / L lithium diisopropylammonium solution to a 250mL flask, cool to -78°C, and add 21.5g (2.5eq) 1,4-butyrolactone dropwise. After the dripping is completed, heat and stir for 2 hours, and then drip 15.6g (1.0eq, 0.1mol) 1,4-dioxaspiro[4,5]dec-2-one (compound of formula IV) in tetrahydrofuran. After the reaction was kept for 8 hours, the reaction was quenched with saturated ammonium chloride solution, the temperature was raised to room temperature, the layers were separated, the aqueous phase was extracted with ethyl acetate, the organic phases were combined, and the product was concentrated after concentration, with a yield of 40%.

Embodiment 3

[0054] Under nitrogen protection, add 220mL 1.0mol / L lithium bis(trimethylsilyl)amide (LHMDS) solution to a 250mL flask, cool to -78℃, and add 17.2g (2.0eq) 1,4-butane dropwise ester. After the dripping is completed, heat and stir for 2 hours, and then drip 15.6g (1.0eq, 0.1mol) 1,4-dioxaspiro[4,5]dec-2-one (compound of formula IV) in tetrahydrofuran. After the reaction is kept for 12 hours, the reaction is quenched with saturated ammonium chloride solution, the temperature is raised to room temperature, the layers are separated, the aqueous phase is extracted with ethyl acetate, the organic phases are combined, and the product is obtained after concentration with a yield of 35%.

[0055] Synthesis of formula II compound

[0056] Example one

[0057] 5.04 g (0.035 mol) of compound III was added to a 100 mL autoclave, 50 mL of methanol was added, and the mixture was stirred to dissolve. Use high-purity nitrogen to change the air in the kettle three times, and then add 1.4g (0.05eq)...

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

The invention discloses a method for preparing a Darunavir intermediate and particularly relates to a preparation method of a compound of formula I shown in the description.

Description

Technical field [0001] The invention belongs to the technical field of medicine, and specifically relates to a preparation method of an AIDS drug darunavir intermediate. Background technique [0002] Darunavir (Darunavir) is a drug developed by Johnson & Johnson Pharmaceuticals for the treatment of AIDS. Darunavir Ethanolate was first launched in the United States and Canada in 2006. [0003] English name of Dirui Nawei: [0004] [(3R,3AS,6AR)-2,3,3A,4,5,6A-HEXAHYDROFURO[5,4-B]FURAN-3-YL]N-[(2S,3R)-4-[(4- AMINOPHENYL)SULFONYL-(2-METHYLPROPYL)AMINO]-3-HYDROXY-1-PHENYLBUTAN-2-YL]CARBAMATE [0005] Molecular formula: C27H37N3O7S [0006] Molecular weight: 547.66 [0007] [0008] Darunavir is a new non-peptide antiretroviral protease inhibitor for the treatment of AIDS. It was successfully developed by Tibotec, the Iceland branch of Johnson & Johnson Pharmaceuticals. It is currently six protease inhibitors (saquinavir, ritto). Navir, Indinavir, Nafinavir, Enrenavir and ABT378 / r) have the...

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
Patent Type & Authority Applications(China)
IPC IPC(8): C07D493/04C07D307/33C07D307/60
CPCC07D307/60
Inventor 林文清郑宏杰刘小波朱剑平
Owner 成都博腾药业有限公司
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