Unlock instant, AI-driven research and patent intelligence for your innovation.

Optical activity ring compound preparation method

A compound and hydrate technology, applied in the field of medicine, can solve the problems of poor selectivity, low yield of asymmetric Strecker reaction, etc.

Inactive Publication Date: 2013-04-03
CHINA PHARM UNIV
View PDF5 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] The preparation method involved in the patent CN1680294A has short steps and high optical purity of the product, but has the disadvantages of low asymmetric Strecker reaction yield and poor enantioselectivity

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
  • Optical activity ring compound preparation method
  • Optical activity ring compound preparation method
  • Optical activity ring compound preparation method

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0068] (2S)-2-[1-(diethoxymethyl)cyclopropyl]-2-{[(1R)-(2-hydroxy-1-phenylethyl)amino]}acetonitrile

[0069] 1-(Diethoxymethyl)-cyclopropanecarbaldehyde (3.44 g, 20 mmol) was dissolved in ethanol (20 mL). Sodium bisulfite (2.01g, 19mmol) and sodium cyanide (0.98g, 20mmol) were sequentially added under stirring in an ice bath. A solution of (R)-phenylglycol (2.75 g, 20 mmol) in ethanol (12.5 mL) was slowly added dropwise. React at room temperature for 2 hours and then heat to reflux for 2 hours. Add saturated sodium bicarbonate solution to the reaction solution, extract the aqueous layer with ethyl acetate, wash with saturated brine, dry over anhydrous sodium sulfate, filter, concentrate, flash column chromatography (petroleum ether:ethyl acetate=40:3), A colorless oil was obtained (5.14 g, 81%). 1 HNMR (CDCl 3 , 300MHz) δ0.40~0.72(4H, m), 0.92~1.24(6H, m), 3.30(1H, s), 3.44~3.57(4H, m), 3.65~3.77(3H, m), 3.99~ 4.03(1H, m), 4.77(1H, s), 7.23~7.32(5H, m); ESI-MS m / z: 341.2[...

Embodiment 2

[0080] N-{2-amino-(1S)-1-[1-(diethoxymethyl)cyclopropyl]ethyl}-N-[(1R)-(2-hydroxyl-1-phenylethyl) ] amine

[0081] (2S)-2-[1-(diethoxymethyl)cyclopropyl]-2-{[(1R)-(2-hydroxy-1-phenethyl)amino]}acetonitrile (1.1 g, 3.4 mmol) was dissolved in ethanol (20 mL), 5M NaOH solution (3.9 mL) and Raney nickel (2 g) were added, and stirred at room temperature for 5 hours under hydrogen atmosphere. After filtration, washing and concentration, the mixture was extracted with dichloromethane, washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated to give an oil (0.88 g, 79%). 1 H NMR (CDCl 3 , 300MHz) δ0.21~0.38(2H, m), 0.51~0.60(2H, m), 1.10~1.15(6H, m), 2.19~2.23(1H, m), 2.42(3H, s), 2.76~ 2.81(1H,m), 2.92~2.98(1H,m), 3.33~3.62(4H,m), 3.63~3.74(2H,m), 3.81~3.85(1H,m), 4.31(1H,s), 7.23~7.56(5H, m); ESI-MS m / z: 345.1[M+Na] + ;323.1[M+H] + .

Embodiment 3

[0083] (S)-N-[(1R)-(2-Hydroxy-1-phenylethyl)]-5-azaspiro[2.4]-hept-4-en-7-amine

[0084] N-{2-amino-(1S)-1-[1-(diethoxymethyl)cyclopropyl]ethyl}-N-[(1R)-(2-hydroxyl-1-phenethyl )] The amine (21 g, 0.065 mol) was dissolved in acetone (200 mL). 1mol / L hydrochloric acid (288mL, 2.2mmol) was added under cooling and stirring in an ice bath, and stirred at room temperature for 2 hours. Add saturated sodium bicarbonate solution to alkalinize, extract with ethyl acetate, wash with saturated brine, dry over anhydrous sodium sulfate, filter, and concentrate to give a solid (14.5 g, 97%). 1 H NMR (DMSO, 300MHz) δ0.54~0.60(1H, m), 0.80~0.87(1H, m), 0.90~0.97(1H, m), 1.16~1.22(1H, m), 1.90(1H, br ), 2.77(1H, s), 3.20~3.31(1H, m), 3.36~3.39(1H, m), 3.65~3.73(2H, m), 3.90~3.99(1H, m), 4.85~4.89(1H , t, J=12Hz), 7.19~7.31 (5H, m); ESI-MS m / z: 269.1 [M+K] + ;253.1[M+Na] + ;231.2[M+H] + .

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 present invention relates to a new preparation method for a pure stereoisomer of an optical activity azaspiro compound, wherein the compound can be used as an intermediate for preparing an excellent antibacterial drug quinolone derivative. The preparation method has characteristics of easily available raw materials, less steps and high yield, wherein the obtained chiral isomer has high optical purity. The present invention further relates to useful novel compounds in the preparation method.

Description

technical field [0001] The invention relates to the technical field of medicine, in particular to a new preparation method of a pure stereoisomer of an optically active amino-substituted azaspiro compound, which can be used as a raw material for the preparation of excellent antibacterial quinolone derivatives, and relates to Intermediate compounds useful in the production process. Background technique [0002] Sitafloxacin, the chemical name is 7-[(7s)-7-amino-5-azaspiro[2.4]hept-5-yl]-8-chloro-6-fluoro-1-[(1R,2S) -cis-2-fluorocyclopropyl]-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid is a broad-spectrum fluoroquinolone antibacterial drug developed by Japan's Daiichi Pharmaceutical Company, with good It has excellent pharmacokinetic properties, less adverse reactions, and its in vitro antibacterial activity is significantly higher than most similar drugs. It not only increases the antibacterial activity against Gram-positive bacteria, but also has antibacterial activity agai...

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): C07C255/31C07C217/44C07D209/54
CPCY02P20/55
Inventor 孙宏斌徐黎
Owner CHINA PHARM UNIV