.

Pharmaceutical Business Intelligence

  • Anticipate P&T budget requirements
  • Evaluate market entry opportunities
  • Find generic sources and suppliers
  • Predict branded drug patent expiration

► Plans and Pricing

Upgrade to enjoy subscriber-only features like email alerts and data export. See the Plans and Pricing

DrugPatentWatch Database Preview

Claims for Patent: 8,426,586

« Back to Dashboard

Claims for Patent: 8,426,586

Title:Process for preparing amino crotonyl compounds
Abstract: An improved process for preparing 4-[(3-chloro-4-fluorophenyl)amino]-6-{[4-(N,N-dimethylamino)-1-oxo-2-bute- n-1-yl]amino}-7-((S)-tetrahydrofuran-3-yloxy)-quinazoline and related aminocrotonyl compounds and the preparation of a suitable salt of 4-[(3-chloro-4-fluorophenyl)amino]-6-{[4-(N,N-dimethylamino)-1-oxo-2-bute- n-1-yl]amino}-7-((S)-tetrahydrofuran-3-yloxy)-quinazoline for use as a pharmaceutically active substance.
Inventor(s): Soyka; Rainer (Biberach, DE), Rall; Werner (Mittelbiberach, DE), Schnaubelt; Juergen (Oberhoefen/Warthausen, DE), Sieger; Peter (Mittelbiberach, DE), Kulinna; Christian (Attenweiler, DE)
Assignee: Boehringer Ingelheim International GmbH (Ingelheim am Rhein, DE)
Application Number:11/457,622
Patent Claims: 1. A process for preparing a compound of the formula (VII) ##STR00013## wherein X denotes a methyne group or a nitrogen atom, R.sub.a denotes a benzyl, 1-phenylethyl or 3-chloro-4-fluorophenyl group and R.sup.3 and R.sup.4 denote a straight-chain or branched C.sub.1-4-alkyl group, comprising the following synthesis steps: a) reacting a compound of the formula (V) ##STR00014## wherein X denotes a methyne group or a nitrogen atom and R.sub.a denotes a benzyl, 1-phenylethyl or 3-chloro-4-fluorophenyl group, in suitable solvents after corresponding activation with di-(C.sub.1-4-alkyl)-phosphonoacetic acid and b) reacting the resulting compound of the formula (VI) ##STR00015## wherein X denotes a methyne group or a nitrogen atom, R.sub.a denotes a benzyl, 1-phenylethyl or 3-chloro-4-fluorophenyl group and R.sup.1 denotes a straight-chain or branched C.sub.1-4-alkyl group, with the aldehyde of formula ##STR00016## wherein R.sup.3 and R.sup.4 in each case represent a straight-chain or branched C.sub.1-C.sub.4-alkyl group, while the groups may be identical or different, or a corresponding aldehyde equivalent, using suitable organic or inorganic bases.

2. A process for preparing 4-[(3-chloro-4-fluorophenyl)amino]-6-{[4-(N,N-dimethylamino)-1-oxo-2-bute- n-1-yl]amino}-7- ((S)-tetrahydrofuran-3-yloxy)-quinazoline, comprising the following synthesis steps: a) reacting N.sup.4-(3-chloro-4-fluoro-phenyl)-7-(tetrahydrofuran-3-yloxy)quinazoline- -4,6-diamine in suitable solvents after corresponding activation with di-(C.sub.1-4-alkyl)-phos -phonoacetic acid and b) reacting the resulting dialkylester {[4-(3-chloro-4-fluoro-phenylamino)-7-((S)-tetrahydrofuran-3-yloxy)-quina- zolin-6-ylcarbamoyl]-methyl}-phosphonate with the aldehyde prepared in situ from the corresponding (dimethylamino)-acetaldehyde-dialkylacetal using suitable organic or inorganic bases.

3. The process according to claim 2, wherein in step a) diethylphosphonoacetic acid is used as reagent.

4. The process according to claim 1, wherein in step b) DBU (1,5-diaza-bicyclo[4.3.0]non-5-ene), sodium hydroxide or potassium hydroxide is used as base.

5. The process according to claim 4, wherein in step b) potassium hydroxide is used as base.

6. A process for preparing the dimaleates of 4-[(3-chloro-4-fluorophenyl)amino]-6-{[4-(N,N-dimethylamino)-1-oxo-2-bute- n-1-yl]amino }-7-((S)-tetrahydrofuran-3-yloxy)-quinazoline, comprising steps a and b according to claim 1 as well as the following step c): c) converting the resulting 4-[(3-chloro-4-fluorophenyl)amino]-6-{[4-(N,N-dimethylamino)-1-oxo-2-bute- n-1-yl]amino}-7-((S)-tetrahydrofuran-3-yloxy)-quinazoline into the dimaleate by reacting with maleic acid in a suitable solvent, with heating.

7. The process according to claim 6, wherein ethanol or isopropanol is used as solvent, optionally with the addition of water.

8. The process according to claim 6, wherein at least 2equivalents of maleic acid are used.

9. Crystalline 4-[(3-chloro-4-fluorophenyl)amino]-6-{[4-(N,N-dimethylamino)-1-oxo-2-bute- n-1-yl]amino}-7-((S))-tetrahydofuran-3-yloxy)-quinazoline dimaleate, characterized by 2 .THETA. [.degree.] values obtained by X-ray powder diffraction using CuK.sub..alpha.1 radiation, .lamda.=1.5418.ANG. in the following table: TABLE-US-00002 2-.THETA. intensity [.degree.] I/I.sub.o [%] 4.91 47 6.42 33 7.47 27 8.13 30 10.37 30 17.19 36 19.43 38 19.91 100 21.33 21 22.94 32 25.56 37.

10. Crystalline 4-[(3-chloro-4-fluorophenyl)amino]-6-{[4-(N,N-dimethylamino)-1-oxo-2-bute- n-1-yl]amino}-7-((S)-tetrahydrofuran-3-yloxy)-quinazoline dimaleate, characterized by 2 .THETA. [.degree.] values obtained by X-ray powder diffraction using CuK.sub..alpha.1 radiation, .lamda.=1.5418 .ANG. in the following table: TABLE-US-00003 2-.THETA. intensity [.degree.] I/I.sub.o [%] 4.91 47 6.42 33 7.47 27 8.13 30 10.37 30 12.91 20 14.94 11 16.58 12 17.19 36 19.43 38 19.91 100 20.84 13 21.33 21 21.58 12 22.25 15 22.94 32 25.56 37.

11. Crystalline 4-[(3-chloro-4-fluorophenyl)amino]-6-{[4-(N,N-dimethylamino)-1-oxo-2-bute- n-1-yl]amino}-7-((S))-tetrahydofuran-3-yloxy)-quinazoline dimaleate, characterized by 2 .THETA. [.degree.] values obtained by X-ray powder diffraction using CuK.sub..alpha.1 radiation, .lamda.=1.5418 .ANG. in the following table: TABLE-US-00004 2-.THETA. d-value intensity [.degree.] [.ANG.] I/I.sub.o [%] 4.91 18.0 47 6.42 13.8 33 7.47 11.8 27 8.13 10.9 30 10.37 8.53 30 11.69 7.56 2 12.91 6.85 20 13.46 6.58 3 13.66 6.48 2 14.94 5.93 11 16.58 5.34 12 17.19 5.15 36 17.87 4.96 5 19.43 4.57 38 19.91 4.46 100 20.84 4.26 13 21.33 4.16 21 21.58 4.12 12 22.25 3.992 15 22.94 3.873 32 23.67 3.756 9 24.82 3.584 7 25.56 3.482 37 26.71 3.335 9 27.46 3.245 4 28.37 3.143 8 30.71 2.909 3 29.31 3.045 4 29.57 3.019 4 31.32 2.854 10 32.31 2.769 4 33.10 2.705 5 33.90 2.643 1 34.84 2.573 2 35.71 2.512 1 36.38 2.46 71 36.96 2.430 1 37.99 2.367 2 39.94 2.255 5.
« Back to Dashboard

For more information try a trial or see the database preview and plans and pricing

How are People Using DrugPatentWatch?

Drugs may be covered by multiple patents or regulatory protections. All trademarks and applicant names are the property of their respective owners or licensors. Although great care is taken in the proper and correct provision of this service, thinkBiotech LLC does not accept any responsibility for possible consequences of errors or omissions in the provided data. The data presented herein is for information purposes only. There is no warranty that the data contained herein is error free. thinkBiotech performs no independent verifification of facts as provided by public sources nor are attempts made to provide legal or investing advice. Any reliance on data provided herein is done solely at the discretion of the user. Users of this service are advised to seek professional advice and independent confirmation before considering acting on any of the provided information. thinkBiotech LLC reserves the right to amend, extend or withdraw any part or all of the offered service without notice.

`abc