Welcome to Scribd, the world's digital library. Read, publish, and share books and documents. See more
Download
Standard view
Full view
of .
Look up keyword
Like this
2Activity
0 of .
Results for:
No results containing your search query
P. 1
Complete Specification

Complete Specification

Ratings: (0)|Views: 450 |Likes:
Published by Sai Vinod

More info:

Published by: Sai Vinod on Apr 06, 2012
Copyright:Attribution Non-commercial

Availability:

Read on Scribd mobile: iPhone, iPad and Android.
download as PDF, TXT or read online from Scribd
See more
See less

05/13/2014

pdf

text

original

 
/'
"
(-..l
C
\
_"
..£"",-.
-
.'
'f
,
''',
THEP~TENT~ACT.1970COMPLETE
SPEerFrCA
T~
0N
SECT:rON1.0
TITL.E
CRYSTALMODIFICATIONOFAN-PHENYL-2-PYRIMIDINEAMINEDERIVATIVE,PROCESSESFORITSMANUFACTUREANDITSUSENOVARTISAG
ofSchwarzwaldallee215,4058Basel,Switzerland(aSwisscorporation)Thefollowingspecificationparticularlydescribesandascertainsthenatureofthisinvention,andthemannerinwhichitisto
be.
perf'orme
d
"'THIS
DOCUMENTISSUPPLIED
UNDER
THERIGHT
TO
INFORMATIONACT"
~
 
~""UUtlO/"'"
-1-CrystalmodificationofaN-phenyl-2-oyrimidineaminederivative.processesforilsmanufactureanditsuseTheinventionrelatestoaparticularformofthemethanesulfonicacidadditionsaltof4-(4-methylpipe
razln-t-vlrnethyi
)-N-[4-methyl-3-(4-pyridin-3-yl)pyrimidin-2-ylamino)phenyl]-benzamide,compriSingcertaincrystals,processesforthepreparationthereof,pharma-ceuticalcompositionscontainingthiscrystalform,andtheiruseindiagnosticmethodsorpreferablyforthetherapeutictreatmentofwarm-bloodedanimals,especiallyhumans,ortheiruseforthepreparationofpharmaceuticalpreparationsforuseindiagnosticmethodsorpreferablyforthetherapeutictreatmentofwarm-bloodedanimals.especiallyhumans.Backgroundtotheinvention:Thepreparationof4-(4-methylpiperazin-1-ylmethyl)-N-[4-methyl-3-(4-pyridin-3-yl)pyrimidin-2-ylamino)phenyl]benzamideandtheusethereof,especiallyasananti-tumouragent,aredescribedinExample21of
EP-A-O
564409,whichwaspublishedon6October1993,andinequivalentapplicationsinnumerousothercountries.Thiscompoundisexemplifiedinthesepublicationsonlyinfreeform(notasasalt),IthasnowbeensurpriSinglyfoundthatacrystalformmayundercertainconditionsbefoundinthemethanesulfonatesaltofthiscompound,whichisdescribedhereinafterasJ)-crystalform,andwhichhasveryadvantageousproperties;DetaileddescriptionoftheinventionTheinventionisdescribedinmoredetailinthe,followingwiththehelpofdrawingsandotheraids:DescriptionofthedrawingsFig.
1/3
showstheX-raydiffractiondiagramofthea-crystalformofthemethanesultonicacidadditionsaltofacompoundofformulaI.Fig.2/3showstheX-raydiffractiondiagramofthe~-crystalformofthemethanesulfonicacidadditionsaltofacompoundofformulaI.Fig.
3/3
showsthecrystalsaboveofthec-crystaltermandbelowofthe~-crystalformof4~(4-methylpiperazin-1-ylmethyl)-N-(4-methyl-3-(4-pyridin-3-yl)pyrimidin-2-ylamino)phenyl]-
J~
-ntts
DOCUMENTISSUPPLIEDUNDERTHERIGHTTOINFORMATION
sa:
 
...z-
-
benzamidemethanesulfonate(=ofthemethanesulfonicacidadditionsaltofacompoundofformulaI).InbothX-raydiagrams,theangleofrefraction2thetaisplottedonthehorizontalaxis
(x-
axis)andtherelativelineintensity(background-correctedpeakintensity)onthevertical(y-axis).Thediagramsareobtainedasfollows:first,thex-raydiffractiondiagramisrecordedonfilmusingaGuiniercamera(Enraf-NoniusFR552model)withaGuinier258-94cfilmandcopperradiation(Ka1radiation,wavelength
A.
=
1.54060Angstrom).Theopticaldensityofthelinesonthefilmisproportionaltothelightintensity.Thefilmisthenscannedinusingalinescanner(LS18,Johansson,Taby,Sweden)withSCANPIsoftware.InaccordancewithFig.2/3therearelineshavingarelativelineintensityof20ormoreatthefollowinganglesofrefraction2theta(relativelineintensitiesgiveninparentheses):9.7"
(40),13.9°
(26).14.7"(23).17.5°(57),18.2°(90).20.0°(65),20.6°(76),21.1°(100).22.1°(89),22.7"(38),23.8°
(44),
29.8°(23)and30.8°(20).ThefactthatinFig.213therelativelineintensityofthelineat30.8
0
seemstobehigherthanthatofthelineat29.8
0
isduetoaclosebyfurtherlineat31.0°havingarelativelineintensityof13,MeltingpointsaredeterminedbymeansofaDSCthermogramusingaMettler-ToledoTA8000.DSC("differentialscanningcalorimetry")isthetechniqueofdynamicdifferentialcalorimetry.Usingthistechnique,themeltingtemperaturebothofthe
a-crystal
formandofthe~-crystalformcanbemeasuredbyheatingthesamplesuntilathermal,i.e.anendothermicorexothermic,reactionisdetectedbymeansofultrasensitivesensors.ThemeltingpointsindicatedinthistextaredeterminedusingaMettler-ToledoTA8000apparatus,about
5.5
to6.5mgofeachsamplebeingmeasuredinanaluminiumcruciblewithaperforatedlidunderaquiescentatmosphereofairataheatingrateof
10°C/min
(startingat20°C).Thea-crystalformof4-(4-methylpiperazi1-ylmethyl)-N-[4-methyl-3-(4-pyridin-3-yl)pyrimi-,din-2-ylamino)phenyllbenzamidemethanesulfonateischaracterisedbyneedle-shaped
crystalsandishygroscopic.Inthisform,thecrystalsarenot
particularly
well-suitedto
pharmaceuticalformulationassotiddosageforms,becausetheirphysicalproperties,forexampletheirflowcharacteristics,areunfavourable.Undercertainconditions,however,itis
-THISDOCUMENTISSUPPLIED
UNDERTHERIGHTTOINFORMATIONACT
N
.~.

Activity (2)

You've already reviewed this. Edit your review.
1 thousand reads
1 hundred reads

You're Reading a Free Preview

Download
/*********** DO NOT ALTER ANYTHING BELOW THIS LINE ! ************/ var s_code=s.t();if(s_code)document.write(s_code)//-->