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

Solid forms of 1-ethyl-3-(5-(5-fluoropyridin-3-yl)-7-(pyrimidin-2-yl)-1h-benzo[d]imidazol-2-yl)urea

A fluoropyridine, 137.5ppm technology, used in medical preparations containing active ingredients, antibacterial drugs, drug combinations, etc., can solve problems such as inability to treat and bacterial infections that are difficult to treat with antibiotics

Inactive Publication Date: 2010-12-22
VERTEX PHARMA INC
View PDF5 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Some bacterial infections are difficult or even impossible to treat with antibiotics due to drug resistance

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
  • Solid forms of 1-ethyl-3-(5-(5-fluoropyridin-3-yl)-7-(pyrimidin-2-yl)-1h-benzo[d]imidazol-2-yl)urea
  • Solid forms of 1-ethyl-3-(5-(5-fluoropyridin-3-yl)-7-(pyrimidin-2-yl)-1h-benzo[d]imidazol-2-yl)urea
  • Solid forms of 1-ethyl-3-(5-(5-fluoropyridin-3-yl)-7-(pyrimidin-2-yl)-1h-benzo[d]imidazol-2-yl)urea

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0226] Form IA is prepared by precipitating compound 1 from an aqueous solution, for example by adjusting the acidic solution to pH 7. In some embodiments, the resulting solid can be triturated with a protic solvent such as methanol (eg, hot methanol). In some embodiments, the aqueous solution of Compound 1 is the product of a chemical synthesis of Compound 1, such as provided in Example 1.

[0227] Form IA is a triclinic P-I system, as observed by single crystal structural data at room temperature, with the following unit cell sizes:

[0228]

[0229] α=82.700(14)°, β=83.793(14)°, γ=72.628(13)°

[0230]

[0231] The single crystal structure of type IA is shown in Fig. 1a and 1b.

[0232] A representative XRPD of Form IA is atfigure 2 available in . Representative peaks observed in XRPD are provided in Table 1 below:

[0233] Table 1: Representative XRPD peaks for Form IA

[0234] horn

2-theta°

d value

Egypt

strength

%

pick

...

Embodiment 1

[0320] Example 1: Synthesis of Compound 6, Form IA

[0321] Compound 6, Form IA was prepared using the synthetic scheme and experiments provided below. Form IA was provided by precipitating the synthesized product from an aqueous solution (ie, neutralizing the aqueous solution) as in the experiments provided following the synthetic scheme.

[0322] Analytical methods used throughout the experiments below include:

[0323] (A) HPLC on a Waters XBridge Phenyl column, 4.6x75mm, 3.5 microns. Mobile phase A was water / 1M ammonium formate, pH 7.0 (99:1). Mobile phase B was ACN / water / 1M ammonium formate, pH 7.0 (90:9:1). Gradient of 10-100% B in 10-12 min. Flow rate 1.2 mL / min. Detection at UV 245nm. T = 30°C.

[0324] (B) LC on Agilent RP18, 4.6x250mm column. mobile phaseACN / H 2 O / TFA (60:40:0.1). Detection at 265nm. Flow rate 1.0 mL / min. Runtime 22 minutes.

[0325] (C) GC on a HP-5 column. Use H 2 As a carrier gas, the temperature gradient is 8-2-10-240. Flow rate 1...

Embodiment 3

[0454] Example 3: Physical Characteristics of Type IIA

[0455] Form IIA is prepared by the following two crystallization methods.

[0456] Method I: EtOH / CH to compound 1 free base (173.5 mg) 2 Cl 2 (1:1, 20 mL) to the suspension was added ethanesulfonic acid (95%, from Aldrich, 1.0 equiv, 38 μL). The mixture was stirred at ~45°C until dissolved. The solution was then filtered, concentrated in vacuo, and the resulting oily residue was redissolved in CH 2 Cl 2 (10 mL), this solution was added dropwise to a stirred solution of diethyl ether (~100 mL). The resulting off-white precipitate was filtered, washed with diethyl ether under nitrogen, and the solid was dried under high vacuum at -40-45°C overnight to afford Form IIA (174.6 mg) as a brown powder: HPLC: Rt = 4.92 min. (Method: solvent B: 0.1% TFA / 1% MeCN / water, solvent D: 0.1% TFA / MeCN. Gradient 10% D to 90% D in 8 min. Flow rate 1 mL / min. Method duration 12 min. Column 1 (YMC 3x150).

[0457] 1 H NMR (CD 3 OD, 5...

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

PropertyMeasurementUnit
solubility (mass)aaaaaaaaaa
melting pointaaaaaaaaaa
melting pointaaaaaaaaaa
Login to View More

Abstract

Solid forms of crystalline1-ethyl-3-(5-(5-fluoropyridin-3-yl)-7-(pyrimidin-2-yl)- 1H-benzo[d]imidazol-2-yl)urea, compositions containing solid forms of crystalline 1- ethyl-3-(5-(5-fluoropyridin-3-yl)-7-(pyrimidin-2-yl)-1H-benzo[d]imidazol-2-yl)urea and methods of using the same are described.

Description

[0001] related application [0002] This application claims priority to US Provisional Patent Application Serial No. 61 / 012,355, filed December 7, 2007. technical field [0003] This application relates to solids of 1-ethyl-3-(5-(5-fluoropyridin-3-yl)-7-(pyrimidin-2-yl)-1H-benzo[d]imidazol-2-yl)urea Form and method of use. Background technique [0004] Bacterial resistance to antibiotics has long been recognized and is now considered a serious health problem worldwide. Some bacterial infections are difficult or even impossible to treat with antibiotics due to drug resistance. This problem has become particularly acute with the recent development of multidrug resistance in certain strains of bacteria such as Streptococcus pneumoniae (SP), Staphylococcus aureus, Mycobacterium tuberculosis and Enterococci. As bacterial resistance to antibiotics has become a major public health problem, there is a continuing need to develop newer and more effective antibiotics. More specific...

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): C07D401/14A61K31/4184A61P31/00
CPCC07D401/14A61P31/00A61P31/04A61P31/06
Inventor R·阿拉高瓦I·卡迪亚拉A·勒提兰张越刚
Owner VERTEX PHARMA INC