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

Solid forms comprising N-(5-tert-butyl-isoxazol-3-yl)-N'-{4-[7-(2-morpholin-4-yl-ethoxy)imidazo[2,1-b][1,3]benzothiazol-2-yl]phenyl}urea, compositions thereof, and uses therewith

A form, solid technology, applied in medical preparations containing active ingredients, drug combinations, anhydride/acid/halide active ingredients, etc., can solve problems such as polymorphism sensitivity

Active Publication Date: 2013-12-25
AMBIT BIOSCIENCES
View PDF58 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Also, multicomponent crystalline forms may be potentially susceptible to polymorphism, where more than one three-dimensional crystalline arrangement may exist for a given multicomponent composition

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 comprising N-(5-tert-butyl-isoxazol-3-yl)-N'-{4-[7-(2-morpholin-4-yl-ethoxy)imidazo[2,1-b][1,3]benzothiazol-2-yl]phenyl}urea, compositions thereof, and uses therewith
  • Solid forms comprising N-(5-tert-butyl-isoxazol-3-yl)-N'-{4-[7-(2-morpholin-4-yl-ethoxy)imidazo[2,1-b][1,3]benzothiazol-2-yl]phenyl}urea, compositions thereof, and uses therewith
  • Solid forms comprising N-(5-tert-butyl-isoxazol-3-yl)-N'-{4-[7-(2-morpholin-4-yl-ethoxy)imidazo[2,1-b][1,3]benzothiazol-2-yl]phenyl}urea, compositions thereof, and uses therewith

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0412] 6.1 Example 1.N-(5-tert-butyl-isoxazol-3-yl)-N'-{4-[7-(2-morpholin-4-yl-ethoxy) Synthesis of imidazo[2,1-B][1,3]benzothiazol-2-yl]phenyl}urea ("Compound B1")

[0413] A. The intermediate 2-amino-1,3-benzothiazol-6-ol was prepared according to a slight modification of the literature method of Lau and Gompf: J. Org. Chem. 1970, 35, 4103-4108. To a stirred solution of thiourea (7.6 g, 0.10 mol) in a mixture of 200 mL ethanol and 9 mL concentrated hydrochloric acid was added a solution of 1,4-benzoquinone (21.6 g, 0.20 mol) in 400 mL hot ethanol. The reaction mixture was stirred at room temperature for 24 hours, then concentrated to dryness. The resulting residue was triturated with hot acetonitrile and the resulting solid was filtered and dried.

[0414] The free base was obtained by dissolving the hydrochloride in water, neutralizing with sodium acetate, and collecting the solid by filtration. Purification by LCMS (M+H=167) and NMR afforded the product (2-amino-1,3-...

Embodiment 2

[0419] 6.2 Example 2.N-(5-tert-butyl-isoxazol-3-yl)-N'-{4-[7-(2-morpholin-4-yl-ethoxy) Alternative Synthesis of Imidazo[2,1-B][1,3]Benzothiazol-2-yl]phenyl}urea ("Compound B1")

[0420] A. To intermediate 2-(4-nitrophenyl)imidazo[2,1-b][1,3]benzothiazol-7-ol (2.24 g, 7.2 mmol) from Example 1B in ethanol (40mL) was added to the suspension in SnCl 2 ·H 2 O (7.90 g, 35 mmol), and heated to reflux. Concentrated HCl was added to the reaction mixture and gradually the form precipitated. The reaction mixture was heated to reflux for 20 hours, then allowed to cool to room temperature. The solution was poured onto ice, neutralized with 10% NaOH, and adjusted to about pH 6. The organic phase was extracted three times with ethyl acetate (80ml x 3). via MgSO 4 The extract was dried and concentrated to give a yellow solid (1.621 g, 80%). The solid was recrystallized from methanol to give pure product (1.355 g, 67%).

[0421]B. To a suspension of the intermediate from Step 2A (0...

Embodiment 3

[0424] 6.3 Example 3.N-(5-tert-butyl-isoxazol-3-yl)-N'-{4-[7-(2-morpholin-4-yl-ethoxy) Extensive Synthesis of Imidazo[2,1-B][1,3]Benzothiazol-2-yl]phenyl}urea (“Compound B1”)

[0425] Figure 66a with Figure 66b A multistep reaction procedure for the preparation of large quantities of compound B1 is described in and further described below.

[0426] Step 1: Preparation of 2-amino-6-hydroxybenzothiazole (intermediate 1) . 2-Amino-6-methoxybenzimidazole was reacted with hot aqueous HBr for about 3 hours, then the clear solution was cooled to ambient temperature overnight. The precipitated solid was collected, dissolved in hot water, and adjusted to pH between 4.5-5.5. The resulting solid was collected, dried and recrystallized from isopropanol. The second crop material was collected. The solid was dried in vacuo to afford Intermediate 1.

[0427] Step 2: Preparation of 2-(4-nitrophenyl)imidazo[2,1-b]benzothiazol-7 alcohol (Intermediate 2). 2-Amino-6-hydroxybenzoth...

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
transmittivityaaaaaaaaaa
Login to View More

Abstract

Solid forms comprising N-(5-tert-butyl-isoxazol-3-yl)-N'-{4-[7-(2-morpholin-4-yl-ethoxy)imidazo[2,1-b][1,3]benzothiazol-2-yl]phenyl}urea, compositions comprising the solid forms, methods of making the solid forms and methods of their use for the treatment of various diseases and / or disorders are disclosed.

Description

[0001] This application claims priority to US Provisional Patent Application No. 60 / 994,635, filed September 19, 2007, which is hereby incorporated by reference in its entirety. 1. Field of invention [0002] The present invention discloses N-(5-tert-butyl-isoxazol-3-yl)-N'-{4-[7-(2-morpholin-4-yl-ethoxy)imidazo[2, Solid form of 1-b][1,3]benzothiazol-2-yl]phenyl}urea, composition comprising the solid form, process for preparing the solid form and its use in the treatment of various diseases and / or disease application. 2. Background technology [0003] For example, considering the combination with existing therapeutic agents such as Gleevec A related drawback, there is a need for new kinase inhibitor compounds. Kinase inhibitor compounds are currently being investigated for the treatment of diseases such as cancer. [0004] The identification and selection of a solid form of a pharmaceutical compound is complicated because changes in the solid form can affect a variety of...

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 Patents(China)
IPC IPC(8): C07D513/04A61K31/5377A61P35/00
CPCC07D513/04A61K31/185A61K31/5377A61P1/04A61P11/00A61P11/02A61P11/06A61P13/12A61P17/02A61P19/02A61P19/10A61P25/00A61P29/00A61P31/04A61P31/12A61P35/00A61P35/02A61P37/02A61P37/06A61P37/08A61P43/00A61P9/10A61P3/10C07D413/04
Inventor 施里帕德·巴维特赖伟斯蒂芬·D·帕伦特梅莱妮·J·罗艾伦·施瓦兹瓦勒莉雅·N·斯摩棱斯克
Owner AMBIT BIOSCIENCES