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

Chiral phosphamide compound and preparation method thereof

A technology of phosphoramides and compounds, applied in the field of bioactive drugs

Inactive Publication Date: 2013-09-11
SHANGHAI JIAO TONG UNIV
View PDF3 Cites 3 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

But so far there is no report on the synthesis of P-chiral organophosphoramide compounds by asymmetric catalytic P-N bond construction method

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
  • Chiral phosphamide compound and preparation method thereof
  • Chiral phosphamide compound and preparation method thereof
  • Chiral phosphamide compound and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0029] Example 1: 7-Hydroxy-6,7-dihydro-5 H - Preparation of pyrrole [1,2-α] imidazole

[0030] Add imidazole (50.0 g, 0.734 mol), glacial acetic acid (3.0 mL, 0.051 mol, 0.07 eq), solvent 1,4-dioxane (500 mL) into a 1 L three-necked flask, and stir to dissolve at room temperature. Then pour freshly steamed acrolein (63.0 mL, 0.943 mol, 1.3 eq) in one go, and reflux for 48 h. Then the volatile solvent was evaporated under reduced pressure, and the obtained solid crude product was separated by column chromatography (EtOAc / MeOH = 3 / 1) to obtain 73.8 g of light yellow solid compound with a yield of 81%.

[0031] 1 H NMR (400 MHz, CDCl 3 ): δ 7.07 (d, J = 1.2 Hz, 1H), 6.85 (d, J = 1.2 Hz, 1H), 5.23 (dd, J = 3.2 Hz, 7.2 Hz, 1H), 4.24-4.16 (m, 1H) , 3.98-3.98 (m, 1H), 3.00-2.88 (m, 1H), 2.64-2.54 (m, 1H).

[0032] 13 C NMR (100 MHz, CDCl 3 ): δ 156.4, 132.5, 114.3, 63.6, 43.2, 36.3.

Embodiment 2

[0033] Example 2: (+)-7-Hydroxy-6,7-dihydro-5 H -pyrrole[1,2-α]imidazole and (-)-7-hydroxy-6,7-dihydro-5 H - Preparation of pyrrole [1,2-α] imidazole

[0034] In a dry 250 mL two-necked bottle, 7-hydroxy-6,7-dihydro-5 H -Pyrrole[1,2-α]imidazole (14.5 g, 0.11 mol) was dissolved in 100 ml of methanol, and (+)-tartaric acid (17.5 g, 0.11 mol, 1.0 eq) in methanol solution 100 mL was added under reflux with stirring, and refluxed for 2 h. After cooling to room temperature, a light yellow solid was precipitated (the solid was basified with an appropriate amount of NaOH to free 7-hydroxyl-6,7-dihydro-5 H -pyrrole[1,2-α]imidazole with an ee value of about 30%). The above-mentioned pale yellow solid was recrystallized several times with 200 mL of methanol and a small amount of water to obtain a solid, which was basified with NaOH, extracted with dichloromethane, and 0.6 g of a white powdery solid was obtained after evaporating the solvent, with a yield of 4%, ee= 99.4% (Daicel CHI...

Embodiment 3

[0035] Example 3: (+)-7-methoxy-6,7-dihydro-5 H - Preparation of pyrrole [1,2-α] imidazole

[0036] Add (+)-7-hydroxy-6,7-dihydro-5 to a dry 25 mL two-necked bottle H -Pyrrole [1,2-α] (50.5 mg, 0.4 mmol), inject dry THF (5 mL), stir to dissolve, add NaH (16.1 mg, 0.4 mmol, 1.0 eq) under nitrogen protection, stir at room temperature for 2 h , then slowly drop into MeI (25.0 μL, 0.4 mmol, 1.0 eq), and stir at room temperature for 15 h. After evaporating the volatile solvent, extract with dichloromethane (15 ml × 3), the combined dichloromethane phase was dried over sodium sulfate, dichloromethane was evaporated under reduced pressure, and silica gel column chromatography (EtOAc / MeOH = 10 / 1 , Rf = 0.44) to obtain 23.8 mg of light yellow oily liquid with a yield of 42%.

[0037] 1 H NMR (400 MHz, CDCl 3 ): δ 7.13 (s, 1 H), 6.92 (d, J = 1.2 Hz, 1H), 4.63 (dd, J = 7.2 Hz, 2.0 Hz, 1H), 4.18-4.10 (m, 1 H), 3.52 (s, 3H), 2.86-2.80 (m, 1H), 2.60-2.46 (m, 1H).

[0038] 13 C N...

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 relates to a chiral phosphamide compound and a preparation method thereof. Expensive agents used in the prior art are replaced by a nucleophilic catalyst, and rigor reaction conditions of the prior art are also replaced. The chiral phosphamide compound is produced by the following steps: a racemate of phosphorus oxychloride and a primary amine or a secondary amine are subjected to asymmetric phosphorylation reaction in the protection of inert gas, and a chiral biimidazole compound is used as the nucleophilic catalyst; and then the chiral phosphamide compound is obtained with high production rate and medium enantioselectivity.

Description

technical field [0001] The present invention relates to a compound in the technical field of bioactive drugs and its preparation method, in particular to a class of chiral phosphoramide compounds and their preparation by asymmetric phosphorylation based on chiral bicyclic imidazole nucleophilic catalysts. method. Background technique [0002] Chiral organophosphorus compounds have special three-dimensional structures and biological activities, so they are widely used in the fields of ligands, catalysts, medicine and pesticides ((a) Imamoto, T.; Tamura, K.; Zhang, Z.; Horiuchi, Y.; Sugiya, M.; Yoshida, K.; Yanagisawa, A.; Gridnev, I. D. J. Am. Chem. Soc. 2011, 133 , 1754-1769. (b) Shaw, S. A.; Aleman, P.; Christy, J.; Kampf, J. W.; Va, P.; Vedejs, E. J. Am. Chem. Soc. 2006, 128 , 925-934. (c) Mikolajczyk, M.; Luczak, J.; Sieroń, L.; Wieczorek, M. W. Tetrahedron 2011, 68 , 126-132. (d) Koyanagi, T.; Okada, H.; Imai, O.; Toki, T.; J. Pesticide Sci. 1997, 22 , 187-1...

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): C07F9/553C07F9/59C07F9/572C07F9/6539C07F9/24C07B53/00B01J31/02
Inventor 张万斌谢芳张振锋刘珊
Owner SHANGHAI JIAO TONG UNIV
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