邻苯二甲酸酐

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Query

QueryResultsDate

90reactionsin

Reaxys

2013-08-0521h:51m:34s(EST)

Searchas:Asdrawn,Nosalts,Nomixtures

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O

O

O

S

O

O

NH

2

H

2

N

N

O

O

S

O

OH

2

N

Rx-ID:28018040ViewinReaxys1/90

YieldConditions&References

89%ExampleName4

TheabovecompoundwaspreparedinaccordancewithExample2usingNJV-dimethyl-4-[2-aminoethyl]benzenesul-

fonamideinsteadoftyramine.λyV-dimethyl-4-(2-aminoethyl)benzene-sulfonamide,whichwassynthesizedasfollows:

Asolutionof4-[2-aminoethyl]benzene-sulfonamide(26.5g,0.1mole)inanhydrousDMF(120ml)wastreatedwith

phthalicanhydride(23.5g,0.2mole),ctionwascooledtoambient

temperatureand1,1'-carbonyldiimidazole(21.5g,0.1mole)wasaddedinsmallportions,andthereactionwasstirred

twavaporatedinvacuo,andtheresiduewaswashedwithwater,dried,

andtrituratedwithethylacetatetogivethephthaloyl-protectedcompoundasawhitesolid:38.1g,89percentyield;1H

NMR(400MHz,4-DMSO)δ2.98(2H,t,J=7.0Hz),3.82(2H,t,J=7.0Hz),7.29(2H,s),7.38(2H,d,J=8.0Hz),7.69

(2H,t,J=8.0Hz),7.76-7.84(4H,m);LRMS(ESI):m/z331(MH4),348(MH+Na);HPLC(method2):ion

ofthephthaloyl-protectedcompound(12.7g,38.6mmole)inanhydrousDMF(120ml)underN2at00Cwas

treatedwithNaH(60percentdispersioninoil;3.5g,88.8mmol)insmallportionsover15minandthereactionwas

thane(4.8ml,77.2mmole)wasthenaddeddropwiover15minand

ultantyellowsuspensionwaspoured

ontoice/water(1.4L),cipitatewascollectedbyfiltration,washedquentiallywith

water,hexane,andetherandthendriedinvacuotogivetheλVV-dimethyl-benzenesulfonamidederivativeasawhite

solid:11.3g,81percentyield;LRMS(ESI):m/z359(MH+),381(MH+Na);HPLC(method2):ionofthe

phthaloyl-protectedcompound(11.3g,31.5mmole)andhydrazinehydrate(4.6ml,44.6mmole)in95percentethanol

(125ml)tesolidthatformedwasremovedbyfiltrationandwashedwithethanol.

Combinedfiltrateandwashingswereconcentratedinvacuo,andthesolidthatformedwasremovedbyfiltrationand

ocedurewa

ractswereconcentratedinvacuotogivethefreeamineasayellowoil:

4.8g,67percentyield;1HNMR(400MHz,CD3OD)δ2.65(6H,s),2.84-2.92(4H,m),7.47(2H,d,J-8.5Hz),7.71

(2H,d,J=8.5Hz);LRMS(ESI):m/z229(MH+),251(MH+Na);HPLC(method2):mpoundwasreacted

withthedichlorotriazinefollowedbythealkylamine,olid(2.2g,

92percent);mp143-1460C;1HNMR(400MHz,CD3OD)δ1.42-1.53(2H,m),1.64-1.78(4H,m),2.602.64(6H,2x

s),2.92-2.99(2H,m),3.01-3.07(2H,m),3.39-3.48(2H,m),3.68-3.78(2H,m),6.83-6.92(IH,m),7.24-7.37(2H,m),

7.42-7.71(5H,m);LRMS(ESI):m/z517(MH+),539(MH+Na);HPLC(method1):4.3min.

Stage1:inN,N-dimethyl-formamide,Time=4h,T=70°C

Stage2:With1,1'-carbonyldiimidazoleinN,N-dimethyl-formamide,T=20°C

Patent;PROMETICBIOSCIENCESINC.;WO2008/131547;(2008);(A1)English

ViewinReaxys

O

O

O

NH

2

F

F

N

NH

2

H

2

N

N

N

O

O

F

NH

2

N

FO

O

Rx-ID:35200864ViewinReaxys2/90

YieldConditions&References

80%ExampleTitle2.3.44-Amino-2,6-bis(phthalimido)-3,5-difluoropyridine(DI)(Scheme1)

Themixtureof2FPyTA(0.5g,3.1mmol),PA(0.92g,6.2mmol),andbenzoicacid(3g)washeatedat130°Сupon

stirringincacidwasremovedby

sublimationandthecrudeproductthusobtainedwasrecrystallizedfromDMA,yield1.04g,301–302°C;

IR(KBr):ν3228,3340,1641(NH

2

),3103(C

ar

–H);1790(C=hing),1732(C=hing),1620

(C=C

ar

),1485(Ar

F

),1365(C–Nstretching),1150,883(C–F),715(C=Obending)cm−1;1HNMR(pyridine-d

5

):δ7.61,

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7.78(bothm,both4H,H3′,H4′,H5′,H6′),8.14(br.s,2H,NH

2

);19FNMR(pyridine-d

5

):δ−141.6(s,F3,F5);HRMS

calcd420.0665,C

21

H

10

F

2

N

4

O

4

,found420.0664.

Withbenzoicacid,Time=3h,T=130°C

Vaganova,TamaraA.;Shundrina,InnaK.;Kusov,SoltanZ.;Rodionov,VladimirI.;Malykhin,EvgenijV.;Journal

ofFluorineChemistry;vol.149;(2013);p.57-64,8

ViewinReaxys

O

O

O

NH

2

OH

O

O

H

2

N

H

N

O

O

HO

O

O

NH

2

H

Rx-ID:27910025ViewinReaxys3/90

YieldConditions&References

72%ExampleName1

Example1:PreparationofN-Phthaloyl-L-glutamine:Toadrythreeneckedflaskaddeddrydimethylformamide

(DMF)(60ml)andL-glutamine(2Og,136mmole).esultingsolutionaddedphthali-

canhydride(20g,135mmole)dfor3hratthistemperature,cooledto650C,anddistilled

dDMwater(120ml).dfor2hrat

15°ed,washedwithDMwater(40ml).DriedtogetN-phthaloyl-Lglutamine(27g,97.8mmole,72percent)as

awhitesolid,m.p.,(dmso-d

6

):δ13.20(brs,IH,COOH),8.05-7.75(m,4H,Ar),7.22(s,IH,

CONH

2

),6.72(s,lH,CONH

2

),4.72(dd,IH

5

CH),2.50-1.95(m,4H,CH

2

CH

2

),2.15-2.00(m,IH,CH

2

).13CNMR(dmso-

d

6

):δ173.0,170.4,167.3,134.7,131.2,123.3,51.2,31.3,23.9.

Stage1:inN,N-dimethyl-formamide,Time=3h,T=90-95°C

Stage2:Withhydrogenchloride,water,Time=2h,T=15°C,pH=1.2

Patent;MATRIXLABORATORIESLTD;WO2008/35378;(2008);(A2)English

ViewinReaxys

~52.9%ExampleName1

Example1:PreparationofN-phtiialoyl-L-glutamineToasuspensionofphthalicanhydride(11.1gor0.076mol)in

dimethylformamide(DMF)(62ml),L-glutamine(10gor0.067mol)wasaddedandthemixturewasheatedtoatem-

peratureof90°Cto95°Cforaperiodof6to8hours(oruntilcompletionofthereaction).Whenthereactionwas

complete,theexcesssolventwasremovedbydistillationat65°Cto70°iduewas

cooledtoatemperatureof25°Cto30°Candwater(100ml)utionwasacidifiedwithaqueous

hydrochloricacid(50percent)ultingN-phthaloyl-L-glutaminewas

isolatedbyfiltration,ductwasfinallydriedtoaconstantweightata

temperatureof55°Cto60°Cundervacuum(80to100mmHg):9.5to11g(-52.9per-

centmolar)

Stage1:inN,N-dimethyl-formamide,T=90-95°C

Stage2:Withhydrogenchlorideinwater,T=25-30°C

Patent;GENERICS[UK]LIMITED;MYLANINDIAPRIVATELIMITED;GORE,Vinayak,Govind;SHUKLA,Vinay,

Kumar;PATIL,Madhukar;MEKDE,Sandeep;WO2011/154739;(2011);(A1)English

ViewinReaxys

ExampleName1;3;9-10

L-glutamine(10Og)andphthalicanhydride(14Og)weresuspendedintoluene(1liter)inaflaskprovidedwithadean

ylamine(100ml)tentsoftheflaskwereheatedgradually

to110°ompletionofreaction,

thereactionmasswascooledto50-60°Candaceticanhydride(200ml)ulting

suspensionwasheatedat1100C,id

wasfilteredanddriedat50-550Ctoobtainthalidomide(80g).;L-glutamine(100g)andphthalicanhydride(135g)were

suspendedintoluene(1liter)ylamine(135ml)wasadded

ergeneratedduringthecourofreaction

ompletionofreaction,thereactionmasswascooledto50-60°Candacetylchloride

(200ml)ultingsuspensionwasheatedat1100C,maintainedforaboutthreehours

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idwasfilteredanddriedat50-550Ctoobtainthalidomide

(65g).;L-glutamine(100g)andphthalicanhydride(125g)weresuspendedintoluene(1liter)inaflaskprovidedwitha

ylamine(100ml)tentsoftheflaskwereheated

ompletion

ofreaction,anhydride(200ml)ction

masswasheatedat120°anhydridewasdistilledoutundervacuum

redalcohol(200ml)wasaddedtotheresidue,refluxedforabouthalfanhourandcooledto

idwasfilteredanddriedundervacuumtoobtainthalidomide(65g).;L-glutamine

(100g)andphthalicanhydride(135g)weresuspendedintoluene(1liter)inaflaskprovidedwithadeanstarkwater

ylamine(100ml)tentsoftheflaskwereheatedgraduallyto11O0C.

Thewaompletionofreaction,toluene

chloride(20OmI)wasaddedslowlytotheflaskfollowedbyN,N-dimethylfor-

mamide(200ml).Thetechloride

redalcohol(200ml)wasaddedtotheresidue,refluxedfor

idwasfilteredanddriedundervacuumtoobtain

thalidomide(55g).

Withtriethylamineintoluene,T=110°C,Productdistribution/lectivity

Patent;CIPLALIMITED;CURTIS,Philip,Anthony;WO2009/83724;(2009);(A1)English

ViewinReaxys

ExampleName7

L-glutamine(100g)andphthalicanhydride(125g)suspendedinchlorobenzene(1liter)inaflaskprovidedwithadean

starkwaterparatorfollowedbytriethylamine(135ml).Thecontentsoftheflaskwereheatedgraduallyto11O0C.

Thewaompletionofreaction,the

reactionmasswascooledto50-600Candaceticanhydride(200ml)ultingsuspension

washeatedto1100C,idwasfiltered

anddriedat50-550Ctoobtainthalidomide(72g).

Withtriethylamineinchlorobenzene,T=110°C,Productdistribution/lectivity

Patent;CIPLALIMITED;CURTIS,Philip,Anthony;WO2009/83724;(2009);(A1)English

ViewinReaxys

ExampleName5

L-glutamine(100g)andphthalicanhydride(14Og)weresuspendedinxylene(1liter)inaflaskprovidedwithadean

starkwaterparatorfollowedbytriethylamine(130ml).

waompletionofreaction,thereaction

masswascooledto50-600Candaceticanhydride(200ml)ultingsuspensionwas

heatedat1100C,idwasfilteredand

driedat50-550Ctoobtainthalidomide(73g).

Withtriethylamineinxylene,T=140°C,Productdistribution/lectivity

Patent;CIPLALIMITED;CURTIS,Philip,Anthony;WO2009/83724;(2009);(A1)English

ViewinReaxys

N

N

NH

2

O

O

H

2

N

O

O

O

N

N

H

2

N

O

N

O

O

O

Rx-ID:25753477ViewinReaxys4/90

YieldConditions&References

72%ExampleName8

Example8;SynthesisofCompoundIb-36Amixtureof10,11-dimethoxy-4-methyldibenzo[c,f]-2,7-naphthyridine-3,6-

diamine(1.0g,3.0mmol),phthalicanhydride(0.46g,3.1mmol)andaceticacid(10mL)washeatedto115°

theresultantreactionwasallowedtostirfor48hours,ultantreactionmixture

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wasconcentratedinvacuoandtheresultantresiduewasdilutedwithethylacetate(250mL).Theresultantsolution

waswashedwithaqueoussodiumhydroxide(1N),aniclayerwascollected,driedoversodium

ultantresiduewaspurifiedusingflashcolumnchromatography(silicagel

with3percentmethanol/methylenechlorideeluent)toprovideCompoundIb-36asayellowsolid(1.0g,72percent).MS

465[M+H],HPLC:Rt=2.34minutes

Withaceticacid,Time=48h,T=115°C

Patent;Wyeth;US2007/135429;(2007);(A1)English

ViewinReaxys

O

O

O

S

O

O

NH

2

H

2

N

N

O

O

S

O

O

NH

2

Rx-ID:86842ViewinReaxys5/90

YieldConditions&References

90%Withaceticacid,Time=2h,T=130°C

Santos,JeanL.;Yamasaki,PauloR.;Chin,ChungMan;Takashi,CelioH.;Pavan,FernandoR.;Leite,Clarice

Q.F.;BioorganicandMedicinalChemistry;vol.17;nb.11;(2009);p.3795-3799

ViewinReaxys

89%inaceticacid,Time=55h,Reflux

Davood,Asghar;Azimidoost,Leila;Rahmatpour,Somaieh;Amini,Mohn;Nikbakht,Ali;Shafaroodi,Hamed;

Ansari,Abdollah;Iman,Maryam;MedicinalChemistryRearch;vol.22;nb.7;(2013);p.3177-3184,8

ViewinReaxys

Withaceticacid,ErhitzendesReaktionsproduktsmitNitrobenzol

Cymerman-Craig;Willis;JournaloftheChemicalSociety;(1955);p.1071,1074

ViewinReaxys

Wanag;Veinbergs;ChemischeBerichte;vol.75;(1942);p.1558,1567

ViewinReaxys

Withaceticacid,Time=24h,Reflux

Al-Suwaidan,IbrahimA.;Alanazi,AmerM.;El-Azab,AdelS.;Al-Obaid,AbdulrahmanM.;Abdel-Aziz,AlaaA.-

M.;Eltahir,KamalE.H.;Maarouf,AzzaR.;AbuEl-Enin,MohamedA.;BioorganicandMedicinalChemistryLetters;

vol.23;nb.9;(2013);p.2601-2605,5

ViewinReaxys

O

O

O

NH

2

H

2

N

S

HO

O

O

S

HO

O

O

N

O

ONH

2

Rx-ID:8994575ViewinReaxys6/90

YieldConditions&References

92%inxylene,Heating

Kaik,M.;Gawronski,J.;Tetrahedron:Asymmetry;vol.14;nb.11;(2003);p.1559-1564

ViewinReaxys

92%inanhydrousxylene,Time=5h,Heating

Bui,Tommy;Syed,Salahuddin;Barbas,;JournaloftheAmericanChemicalSociety;vol.131;(2009);

p.8758-8759

ViewinReaxys

90%inxylene,Heating

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Gawronski,Jacek;Gawronska,Krystyna;Grajewski,Jakub;Kacprzak,Karol;Rychlewska,Urszula;Chemical

Communications(Cambridge,UnitedKingdom);nb.6;(2002);p.582-583

ViewinReaxys

O

O

O

N

NH

2

S

H

2

N

NN

O

OS

NH

2

Rx-ID:10934194ViewinReaxys7/90

YieldConditions&References

90%With4-(N,N-dimethlyamino)pyridineinN,N-dimethyl-formamide,Time=3h,Reflux

Cavalcanti,SuellenM.T.;Coelho,LucasCunhaD.;Hernandes,MarceloZ.;Leite,AnaCristinaL.;Souza,Val-

deniaM.O.;Pessoa,Claudia;Ferreira,PauloMichelP.;Lotufo,LeticiaVerasC.;DeMoraes,ManoelO.;DeSi-

mone,CarlosA.;Costa,VlaudiaM.A.;ChemMedChem;vol.5;nb.4;(2010);p.523-528

ViewinReaxys

ExampleName11I

Compound5a(2.1g,20mmole)andphthalicanhydride(3g,20.3mmole)weredissolvedinDMF(20ml),themixture

er(150ml)wasaddedtoquenchthereaction,theprecipitatewascollectedand

driedtogivecrude6(3.5g)nd6a(3.2g,12.4mmole)andbromoa-

cetaldedydediethylacetal(6g,30.5mmole)THFsolution(30ml)twascooled

down,thesolventandtheexcessreagentwereevaporated,andtheresiduewassubjectedtosilicagelcolumnchro-

matography(Hexanes/EtOAc)togive7(1.6g,6mmole,48percent).Toan(1.6g,6mole)ethanolsolutionofCompound

7a(15ml)wasaddedhydrazinehydrate(500mg,10mmole),andthemixturewasrefluxedfor30minat1200C,thenit

wascooleddowntort,ationofthemotherliquorwassubjected

tosilicagelcolumnchromatography(hexanes/EtOAc)lonicacidandEDCinDMF,8a

wasconvertedintoCompound71.1H-NMR(CD

3

OD)δ,10.12(s,2H),7.20-6.24(m,4H)3.52-3.12(m,8H).ESMSclcd

forCH

I4

N

6

O

2

S

2

:326.1;Found:327.1.(M+H)+

inN,N-dimethyl-formamide,Time=2h,T=120°C

Patent;SYNTAPHARMACEUTICALCORP.;WO2008/24302;(2008);(A2)English

ViewinReaxys

O

O

O

NH

2

H

2

NN

O

O

H

2

N

Rx-ID:9299884ViewinReaxys8/90

YieldConditions&References

90.0%inN,N-dimethyl-formamide,Time=4h,T=150°C

Chang,Yao-Te;Shu,Ching-Fong;Macromolecules;vol.36;nb.3;(2003);p.661-666

ViewinReaxys

O

O

O

NH

2

H

2

N

N

O

O

NH

2

Rx-ID:10382227ViewinReaxys9/90

YieldConditions&References

90%Withaceticacid,T=100°C

Dong,Zhenzhen;Liu,Xiaozhong;Yap,GlennP.A.;Fox,JophM.;JournalofOrganicChemistry;vol.72;nb.2;

(2007);p.617-625

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O

O

O

O

NH

O

Cl

NH

2

O

N

H

2

N

N

O

O

N

O

NH

O

O

Cl

NH

2

Rx-ID:24875589ViewinReaxys10/90

YieldConditions&References

2.5parts

(42,4%)

ExampleName20

ExampleTitleExample20

Example20

Amixtureof1.85partsof1,3-isobenzofurandione,4.4partsofcis-4-amino-N-[1-(3-aminopropyl)-3-methoxy-4-piperi-

dinyl]-5-chloro-2-methoxybenzamideand45partsofmethylbenzenewasstirredfor3hoursatrefluxtemperature,using

awaterparator.

Thereactionmixturewavaporated.

Theresiduewastakenupintrichloromethane.

Theorganicphawaswashedwithasaturatesolutionofsodiumcarbonateandwater,dried,filteredandevaporated.

Theresiduewaspurifiedbycolumnchromatographyoversilicagelusingamixtureoftrichloromethaneandmethanol,

saturatedwithammonia,(97:3byvolume)aluent.

Thepurefractionswerecollectedandtheeluentwavaporated.

Theresiduewascrystallizedfromacetonitrile.

Theproductwasfilteredoffanddried,yielding2.5parts(42,4percent)ofcis-4-amino-5-chloro-N-[1-[3-(1,3-dihydro-1,3-

dioxo-2H-isoindol-2-yl)propyl]-3-methoxy-4-piperidinyl]-2-methoxybenzamide;mp.208.2°C.(compound88).

Withsodiumcarbonateinmethanol,chloroform,water

Patent;JansnPharmaceuticalN.V.;US4975439;(1990);(A1)English

ViewinReaxys

O

O

O

NH

2

H

2

N

N

O

O

NH

2

Rx-ID:28705165ViewinReaxys11/90

YieldConditions&References

95%Withaceticacid,Time=1h,T=100°C

Tandon,VishnuK.;Maurya,HardeshK.;Mishra,NripendraN.;Shukla,PraveenK.;EuropeanJournalofMedicinal

Chemistry;vol.44;nb.8;(2009);p.3130-3137

ViewinReaxys

O

O

O

HN

O

NH

2

H

2

N

N

O

O

N

H

O

NH

2

Rx-ID:9638434ViewinReaxys12/90

YieldConditions&References

57%With4-(N,N-dimethlyamino)pyridineinN,N-dimethyl-formamide,Time=3h,Reflux

Cavalcanti,SuellenM.T.;Coelho,LucasCunhaD.;Hernandes,MarceloZ.;Leite,AnaCristinaL.;Souza,Val-

deniaM.O.;Pessoa,Claudia;Ferreira,PauloMichelP.;Lotufo,LeticiaVerasC.;DeMoraes,ManoelO.;DeSi-

mone,CarlosA.;Costa,VlaudiaM.A.;ChemMedChem;vol.5;nb.4;(2010);p.523-528

ViewinReaxys

32%inaceticacid

Yogeeswari,P.;Sriram,D.;Saraswat,V.;Ragavendran,da;Kumar,;Murugesan,S.;Thir-

umurugan,R.;Stables,J.P.;EuropeanJournalofPharmaceuticalSciences;vol.20;nb.3;(2003);p.341-346

ViewinReaxys

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O

O

O

HN

S

NH

2

H

2

N

N

O

O

N

H

S

NH

2

Rx-ID:9638435ViewinReaxys13/90

YieldConditions&References

61%With4-(N,N-dimethlyamino)pyridineinN,N-dimethyl-formamide,Time=3h,Reflux

Cavalcanti,SuellenM.T.;Coelho,LucasCunhaD.;Hernandes,MarceloZ.;Leite,AnaCristinaL.;Souza,Val-

deniaM.O.;Pessoa,Claudia;Ferreira,PauloMichelP.;Lotufo,LeticiaVerasC.;DeMoraes,ManoelO.;DeSi-

mone,CarlosA.;Costa,VlaudiaM.A.;ChemMedChem;vol.5;nb.4;(2010);p.523-528

ViewinReaxys

51%inaceticacid

Yogeeswari,P.;Sriram,D.;Saraswat,V.;Ragavendran,da;Kumar,;Murugesan,S.;Thir-

umurugan,R.;Stables,J.P.;EuropeanJournalofPharmaceuticalSciences;vol.20;nb.3;(2003);p.341-346

ViewinReaxys

O

O

O

NH

2

O

H

2

N

OH

O

H

N

O

O

O

NH

2

HO

O

H

Rx-ID:28567938ViewinReaxys14/90

YieldConditions&References

ExampleName2;4

L-isoglutamine(100g)andphthalicanhydride(12Og)weresuspendedintoluene(1liter)inaflaskprovidedwithadean

ylamine(120ml)tentsoftheflaskwereheatedgradually

ompletionofreaction,

thereactionmasswascooledto50-600Candaceticanhydride(200ml)ultingsus-

pensionwasheatedat110°C,idwas

filteredanddriedat50-550Ctoobtainthalidomide(75g).;L-isoglutamine(100g)andphthalicanhydride(14Og)were

suspendedintoluene(1liter)ylamine(135ml)wasadded

ergeneratedduringthecourofreaction

ompletionofreaction,thereactionmasswascooledto50-600Candacetylchloride

(200ml)ultingsuspensionwasheatedat1100C,maintainedforabout

idwasfilteredanddriedat50-550Ctoobtainthalidomide

(68g).

Withtriethylamineintoluene,T=110°C,Productdistribution/lectivity

Patent;CIPLALIMITED;CURTIS,Philip,Anthony;WO2009/83724;(2009);(A1)English

ViewinReaxys

ExampleName8

L-isoglutamine(100g)andphthalicanhydride(14Og)suspendedinchlorobenzene(1liter)inaflaskprovidedwitha

deanstarkwaterparatorfollowedbytriethylamine(135ml).Thecontentsoftheflaskwereheatedgraduallyto110°C.

Thewaompletionofreaction,the

reactionmasswascooledto50-600Candacetylchloride(200ml)ultingsuspension

washeatedto110°C,idwasfiltered

anddriedat50-550Ctoobtainthalidomide(75g).

Withtriethylamineinchlorobenzene,T=110°C,Productdistribution/lectivity

Patent;CIPLALIMITED;CURTIS,Philip,Anthony;WO2009/83724;(2009);(A1)English

ViewinReaxys

ExampleName6

L-isoglutamine(100g)andphthalicanhydride(14Og)weresuspendedinxylene(1liter)inaflaskprovidedwithadean

starkwaterparatorfollowedbytriethylamine(100ml).Thecontentsoftheflaskwereheatedgraduallyto140°

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waompletionofreaction,thereaction

masswascooledto50-60°Candaceticanhydride(200ml)ultingsuspensionwas

heatedat110°C,maintainedforaboutthreehoursandcooledtoidwas

filteredanddriedat50-550Ctoobtainthalidomide(65g).

Withtriethylamineinxylene,T=140°C,Productdistribution/lectivity

Patent;CIPLALIMITED;CURTIS,Philip,Anthony;WO2009/83724;(2009);(A1)English

ViewinReaxys

O

O

O

S

O

O

NH

2

H

2

N

S

O

O

N

NH

2

O

O

Rx-ID:87121ViewinReaxys15/90

YieldConditions&References

37%Withaceticacid,Time=2h,T=130°C

Santos,JeanL.;Yamasaki,PauloR.;Chin,ChungMan;Takashi,CelioH.;Pavan,FernandoR.;Leite,Clarice

Q.F.;BioorganicandMedicinalChemistry;vol.17;nb.11;(2009);p.3795-3799

ViewinReaxys

T=200°C

Gray;Platt;JournaloftheChemicalSociety;(1942);p.42,45

ViewinReaxys

Withpyridine

Gray;Platt;JournaloftheChemicalSociety;(1942);p.42,45

ViewinReaxys

O

O

O

I

I

NH

2

H

2

N

N

O

OI

I

H

2

N

Rx-ID:9122485ViewinReaxys16/90

YieldConditions&References

88%Withtriethylamineintoluene,Heating

Larkem,A.;Larkem,H.;IndianJournalofChemistry,SectionB:OrganicChemistryIncludingMedicinalChemistry;

vol.41;nb.1;(2002);p.175-180

ViewinReaxys

O

O

O

O

O

O

N

NH

2

N

H

2

N

N

O

O

N

N

H

2

N

O

O

O

Rx-ID:25328059ViewinReaxys17/90

YieldConditions&References

ExampleName5.a

ExampleTitleEXAMPLE5

(a)

8.7goftrimethoprimaredissolvedin50mlofpyridineatabout50°C.,andthen4.5gofphthalicanhydrideareadded.

Themixtureisstirredforanothertwohoursatfrom80°to90°C.;aftercooling,100mlofwaterareadded.

Theprecipitateiswashedwithwaterandrecrystallizedfromethanol.

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7gof2-phthalimido-4-amino-5-(3,4,5-trimethoxybenzyl)-pyrimidineofmeltingpoint221°ainedasintermedi-

ateproduct.

inpyridine,water

Patent;BASFAktiengellschaft;US4189581;(1980);(A1)English

ViewinReaxys

O

O

O

NH

2

H

2

N

N

O

ONH

2

Rx-ID:25970406ViewinReaxys18/90

YieldConditions&References

Stage1:Withtoluene-4-sulfonicacidino-xylene,Time=8h,Heating

Stage2:Withsodiumhydrogencarbonateindichloromethane,Time=12h,T=20°C,Furtherstages.

Berkesl,Albrecht;Mukherjee,Santanu;Mueller,ThomasN.;Cleemann,Felix;Roland,Katrin;Brandenburg,

Marc;Neudoerfl,Joerg-M.;Lex,Johann;OrganicandBiomolecularChemistry;vol.4;nb.23;(2006);p.4319-4330

ViewinReaxys

Stage1:Withtoluene-4-sulfonicacidinanhydrousxylene,Time=5h,Reflux

Stage2:Withpotassiumcarbonateindichloromethane,Time=10h,T=20°C,Reflux

Huang,Huayin;Zong,Hua;Bian,Guangling;Song,Ling;JournalofOrganicChemistry;vol.77;nb.22;(2012);p.

10427-10434

ViewinReaxys

O

O

O

S

HN

O

O

NH

2

NH

H

2

N

N

O

O

S

NH

O

O

H

2

N

HN

Rx-ID:28662850ViewinReaxys19/90

YieldConditions&References

70%Withaceticacid,Time=2h,T=130°C

Santos,JeanL.;Yamasaki,PauloR.;Chin,ChungMan;Takashi,CelioH.;Pavan,FernandoR.;Leite,Clarice

Q.F.;BioorganicandMedicinalChemistry;vol.17;nb.11;(2009);p.3795-3799

ViewinReaxys

O

O

O

N

H

NH

2

NH

H

2

N

N

O

O

N

H

NH

2

NH

Rx-ID:29902795ViewinReaxys20/90

YieldConditions&References

55%With4-(N,N-dimethlyamino)pyridineinN,N-dimethyl-formamide,Time=3h,Reflux

Cavalcanti,SuellenM.T.;Coelho,LucasCunhaD.;Hernandes,MarceloZ.;Leite,AnaCristinaL.;Souza,Val-

deniaM.O.;Pessoa,Claudia;Ferreira,PauloMichelP.;Lotufo,LeticiaVerasC.;DeMoraes,ManoelO.;DeSi-

mone,CarlosA.;Costa,VlaudiaM.A.;ChemMedChem;vol.5;nb.4;(2010);p.523-528

ViewinReaxys

O

O

O

NH

2

H

2

N

N

O

ONH

2

NH

N

OH

O

Rx-ID:31978922ViewinReaxys21/90

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YieldConditions&References

54%,26%Withwater,Time=1h,T=100°C

Mamada,Masashi;Perez-Bolivar,Cesar;Anzenbacher,Pavel;OrganicLetters;vol.13;nb.18;(2011);p.4882-

4885

ViewinReaxys

O

O

O

S

O

O

NH

2

H

N

H

N

S

H

2

N

N

HN

O

O

HN

S

S

O

O

NH

2

Rx-ID:9638420ViewinReaxys22/90

YieldConditions&References

89%inaceticacid,Time=5h,Heating

Yogeeswari,P.;Sriram,D.;Saraswat,V.;Ragavendran,da;Kumar,;Murugesan,S.;Thir-

umurugan,R.;Stables,J.P.;EuropeanJournalofPharmaceuticalSciences;vol.20;nb.3;(2003);p.341-346

ViewinReaxys

O

O

O

NH

2

H

2

N

N

O

O

NH

2N

O

NH

2

O

Z

Rx-ID:10382228ViewinReaxys23/90

YieldConditions&References

With4-(N,N-dimethlyamino)pyridine,1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimidehydrochlorideindichlorome-

thane,Time=16h,T=20°C

Dong,Zhenzhen;Liu,Xiaozhong;Yap,GlennP.A.;Fox,JophM.;JournalofOrganicChemistry;vol.72;nb.2;

(2007);p.617-625

ViewinReaxys

O

O

O

NH

2

OH

O

O

H

2

N

H

N

O

O

HO

O

O

NH

2

H

Rx-ID:23739900ViewinReaxys24/90

YieldConditions&References

ExampleName1;2;3

L-glutamine(10g;68.42mmoles)issuspendedinpyridine(50ml)icanhydride(14g,94.5

mmoles)isaddedandthemixtureisgraduallyheatedtoT=80-85°6h,analiquotofthereactionmixtureis

distilledoffundervacuumandthemixtureiscooledto40°yl-diimidazole(12g,74mmoles)isaddedin

portions,keepingunderstirringfor2h,thereafterthemixtureisconcentratedundervacuumtoaboutonefifthofthe

startingvolume,cooledto25°C,thendilutedwithacold(approx.5°C)4:1water-ethanolmixture(100ml).Aqueous

hydrochloricacid(37percent)isdroppedtoadjustthepHto7.0+/-tureisleftunderstirringfor4huntilit

warmsuptoroomtemperature,thentheprecipitatedsolidisfilteredbysuctionandwashedtwicewith25mlofwater.

Theresultingsolidisthendriedovernightundervacuumat40°C,togiveawhitecrystallineproduct(10.6g;yield:

60percentonglutamine).;Example25g(34.21mmoles)ofL-glutaminearesuspendedin25mlofpyridineina100

ml5-neckround-bottomflaskatroomtemperature,followedbyadditionof5g(33.80mmoles)ofphthalicanhydride

andthemixtureisheatedtoT=80-85°C.6hrslateranaliquotofthereactionmixtureisdistilledundervacuum,then

cooledto40°C.3.1g(45.5mmoles)ofimidazoleareloadedintheflask,whichisthencooledto5-10°C,then1.6ml

(22mmoles)tureisstirredatroomtemperaturefor1h,heated

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to85°Candkeptunderstirringatthistemperaturefor3h,idue

iscooledto25°Cand100mlofacold(ca.5°C)(4/1)water/tureisacidified

with37percentHCltopH=7.0+/-0.5andleftunderstirringfor4huntilroomtemperature,thentheprecipitatedsolid

ultingsolidisthendriedovernightundervacuumat

40°Ctogiveawhitecrystallineproduct(3.9g,yield45percent).;Example35g(34.21mmoles)ofL-glutamineare

suspendedin25mlofpyridineina100ml5-neckround-bottomflaskatroomtemperature,followedby5g(33.80

mmoles)tureisheatedtoT=80°Cfor6hrs,thenthesolutioniscooledto5-10°C.2.60

ml(4.2g;35.3mmoles)ofthionylchloridearedroppedwithcautioninthereactionflask,thenthemixtureiscooledto

3hapyridinevolumeofabout80-85percentofthestartingvolumeisdistilledoffandthe

residueiscooledto30-35°C,then100mlofa(4/1)water/tureiscooled

to8-10°Cwithanicebathandacidifiedwith37percentHCl37percenttopH=tureisleftunderstirringfor

4huntilroomtemperature;thepr

resultingsolidisthendriedovernightundervacuumat40°Ctogiveacrystallinewhitesolid(3.6g,yield41percent).

inpyridine,Time=6h,T=20-85°C,Productdistribution/lectivity

Patent;AntibioticosS.p.A.;EP1602654;(2005);(A1)English

ViewinReaxys

ExampleName5

10g(68.42mmoles)ofL-glutaminearesuspendedin50mlofN-methyl-2-pyrrolidoneina250ml5-neckround-bottom

flaskatroomtemperature,followedby10g(67.60mmoles)ofphthalicanhydrideandheatedtoT=80°6hthe

solutioniscooledto30°Candpouredintoaround-bottomflaskcontaining12g(74mmoles)ofcarbonyl-diimidazole

utionisheatedat85-90°Candkeptunder

precipitatedsolidisfiltered,washedtwicewith250mlofwaterandtakenupin100mlof(4/1)water/

filtrationanddryingovernightundervacuumat40°Cacrystallinewhitesolidisobtained(11.5g;24mmoles;Y=65per-

cent).

in1-methyl-pyrrolidin-2-one,Time=6h,T=20-80°C,Productdistribution/lectivity

Patent;AntibioticosS.p.A.;EP1602654;(2005);(A1)English

ViewinReaxys

ExampleName4

10g(68.42mmoles)ofL-glutaminearesuspendedin50mlofDMSOina250ml5-neckround-bottomflaskatroom

temperature,addedwith10g(67.60mmoles)ofphthalicanhydrideandheatedtoT=80°6hthesolutionis

cooledto20°C,filteredandpouredintoaround-bottomflaskcontaining12g(74mmoles)ofcarbonyl-diimidazolein

20mlofDMSOat20°ultingsolutionisheatedto85-90°ution

isthenpouredintoaconicalflaskcontaining500mlofcoldwater(about5°C)andleftunderstirringfor2hatroom

teredsolidisthensuspended

in200mlof(4/1)water/methanolat60°C,filteredanddriedovernightundervacuumat40°C,togiveacrystallinewhite

product(10.9g,yield62percent)..

indimethylsulfoxide,Time=6h,T=20-80°C,Productdistribution/lectivity

Patent;AntibioticosS.p.A.;EP1602654;(2005);(A1)English

ViewinReaxys

ExampleName6

10g(68.42mmoles)ofL-glutaminearesuspendedin50mlofdimethyl-acetamideina250ml5-neckround-bottom

flaskatroomtemperature,followedby10g(67.6mmoles)ofphthalicanhydrideandthemixtureisheatedtoT=80°C.

After6hthesolutioniscooledto30°Canddroppedinaround-bottomflaskcontaining12g(74mmoles)ofcarbonyl-

ultingsolutionisheatedto85-90°C

andkeptunderstirringatthistemperaturefor4h,thenthesolutionispouredintoaconicalflaskcontaining500mlof

cipitatedsolidisfiltered,washedtwicewith250mlofwaterandtakenupin100mlof(4/1)water/

ilteringanddryingovernightundervacuumat40°Cacrystallinewhitesolidisobtained(12.5g;Y=71

percent).

inisobutyramide,Time=6h,T=20-80°C,Productdistribution/lectivity

Patent;AntibioticosS.p.A.;EP1602654;(2005);(A1)English

ViewinReaxys

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O

O

O

NH

2

H

2

N

N

O

ONH

2

N

O

O

N

O

O

Rx-ID:1661080ViewinReaxys25/90

YieldConditions&References

55%inethanol,benzene,Time=2.5h,T=90°C

Jordis,U.;Sauter,F.;Rudolf,M.;Cai,Gan;MonatsheftefuerChemie;vol.119;(1988);p.761-780

ViewinReaxys

O

O

O

HN

O

NH

2

H

2

N

N

O

O

H

2

N

HN

O

Rx-ID:8932616ViewinReaxys26/90

YieldConditions&References

59%inN,N-dimethyl-formamide,Time=12h,Heating

Choi,Dong-Sook;Chong,YongS.;Whitehead,Daniel;Shimizu,KenD.;OrganicLetters;vol.3;nb.23;(2001);

p.3757-3760

ViewinReaxys

N

N

NH

2

N

H

2

N

F

O

O

O

N

O

O

N

N

H

2

N

N

F

Rx-ID:10107444ViewinReaxys27/90

YieldConditions&References

68%innitrobenzene,Time=0.5h,Heating

Falcao,EmersonPeterdaS.;Melo,;Srivastava,RajendraM.;Catanho,MariaTerezaJann

deA.;Nascimento,SileneCarneiroDo;EuropeanJournalofMedicinalChemistry;vol.41;nb.2;(2006);p.276-

282

ViewinReaxys

N

N

NH

2

N

H

2

N

O

O

O

O

N

O

O

N

N

H

2

N

N

O

Rx-ID:10107446ViewinReaxys28/90

YieldConditions&References

67%innitrobenzene,Time=0.5h,Heating

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Falcao,EmersonPeterdaS.;Melo,;Srivastava,RajendraM.;Catanho,MariaTerezaJann

deA.;Nascimento,SileneCarneiroDo;EuropeanJournalofMedicinalChemistry;vol.41;nb.2;(2006);p.276-

282

ViewinReaxys

N

N

NH

2

N

H

2

N

O

O

O

N

O

O

N

N

H

2

N

N

Rx-ID:10107443ViewinReaxys29/90

YieldConditions&References

64%innitrobenzene,Time=0.5h,Heating

Falcao,EmersonPeterdaS.;Melo,;Srivastava,RajendraM.;Catanho,MariaTerezaJann

deA.;Nascimento,SileneCarneiroDo;EuropeanJournalofMedicinalChemistry;vol.41;nb.2;(2006);p.276-

282

ViewinReaxys

N

N

NH

2

N

H

2

N

Cl

O

O

O

N

O

O

N

N

H

2

N

N

Cl

Rx-ID:10107445ViewinReaxys30/90

YieldConditions&References

61%innitrobenzene,Time=0.5h,Heating

Falcao,EmersonPeterdaS.;Melo,;Srivastava,RajendraM.;Catanho,MariaTerezaJann

deA.;Nascimento,SileneCarneiroDo;EuropeanJournalofMedicinalChemistry;vol.41;nb.2;(2006);p.276-

282

ViewinReaxys

O

O

O

N

O

N

N

OH

NH

2

N

H

2

N

OH

N

O

O

OH

O

N

OH

N

N

N

H

2

N

Rx-ID:592747ViewinReaxys31/90

YieldConditions&References

WithN,N-dimethyl-formamide

Bakeretal.;JournaloftheAmericanChemicalSociety;vol.77;(1955);p.5905,5910

ViewinReaxys

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O

O

O

O

O

O

O

H

2

N

O

H

2

N

O

O

O

O

N

O

H

2

N

O

O

racemate

Rx-ID:1661153ViewinReaxys32/90

YieldConditions&References

68%T=220-225°C

Skaric,Vinko;Sedjak,Mirjana;Turjak-Zebic,Vera;Skaric,Djurdjica;CanadianJournalofChemistry;vol.58;

(1980);p.1860-1864

ViewinReaxys

O

O

O

HN

N

N

NH

2

H

2

N

N

N

N

O

O

NH

N

NH

2

N

Rx-ID:4337073ViewinReaxys33/90

YieldConditions&References

17%Withpyridine,Time=3h,T=120°C

Okamoto,Yoshihisa;Zama,Yoshimi;Takagi,Kaname;Kurasawa,Yoshihisa;Harada,Kazuho;Takada,At-

sushi;Heterocycles;vol.41;nb.8;(1995);p.1757-1770

ViewinReaxys

NN

NH

2

N

H

2

N

Cl

O

O

O

N

O

O

N

N

NH

2

N

Cl

Rx-ID:10107447ViewinReaxys34/90

YieldConditions&References

50%innitrobenzene,Time=0.5h,Heating

Falcao,EmersonPeterdaS.;Melo,;Srivastava,RajendraM.;Catanho,MariaTerezaJann

deA.;Nascimento,SileneCarneiroDo;EuropeanJournalofMedicinalChemistry;vol.41;nb.2;(2006);p.276-

282

ViewinReaxys

O

O

O

S

HN

H

2

N

O

O

H

2

N

N

S

HN

O

O

O

NH

2

O

Rx-ID:26060381ViewinReaxys35/90

YieldConditions&References

81%inaceticacid,Time=28h

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Dotnko,V.V.;Krivokolysko,S.G.;Litvinov,V.P.;ChemistryofHeterocyclicCompounds(NewYork,NY,United

States);vol.43;nb.4;(2007);p.519-520;KhimiyaGeterotsiklicheskikhSoedinenii;vol.43;nb.4;(2007);p.623-

624

ViewinReaxys

O

O

O

O

O

NH

2

H

2

N

N

O

O

O

H

2

N

O

Rx-ID:1661141ViewinReaxys36/90

YieldConditions&References

69%inm-xylene,Time=10h,Heating,withwaterparation

Vasil'eva,E.M.;Kolesnikov,V.T.;Slezko,G.F.;JournalofOrganicChemistryUSSR(EnglishTranslation);vol.18;

(1982);p.1704-1707;ZhurnalOrganicheskoiKhimii;vol.18;nb.9;(1982);p.1945-1949

ViewinReaxys

O

O

O

O

F

F

F

H

2

N

OO

F

F

F

F

F

F

NH

2

NH

2

N

O

O

O

F

F

F

O

O

F

F

F

F

F

F

NH

2

NH

2

Rx-ID:29997696ViewinReaxys37/90

YieldConditions&References

Stage1:inN,N-dimethylacetamide,Time=5h,T=40°C,Inertatmosphere

Stage2:inN,N-dimethylacetamide,m-xylene,Time=5h,T=170°C,Inertatmosphere

Gao,Hong;Yan,Changqing;Guan,Shaowei;Jiang,Zhenhua;Polymer;vol.51;nb.3;(2010);p.694-701

ViewinReaxys

O

O

O

O

F

F

F

H

2

N

OO

F

F

F

F

F

F

NH

2

NH

2

N

OO

O

F

F

F

O

O

F

F

F

F

F

F

NH

2

N

O

O

Rx-ID:29997697ViewinReaxys38/90

YieldConditions&References

Stage1:inN,N-dimethylacetamide,Time=5h,T=40°C,Inertatmosphere

Stage2:inN,N-dimethylacetamide,m-xylene,Time=5h,T=170°C,Inertatmosphere

Gao,Hong;Yan,Changqing;Guan,Shaowei;Jiang,Zhenhua;Polymer;vol.51;nb.3;(2010);p.694-701

ViewinReaxys

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O

O

O

NH

2

O

O

H

2

N

N

O

O

O

O

H

2

N

HN

O

O

NH

2

O

OH

O

Rx-ID:1660940ViewinReaxys39/90

YieldConditions&References

15%,61%Time=0.5h,T=140-160°C

Vaidya,V.P.;Agasimundin,Y.S.;IndianJournalofChemistry,SectionB:OrganicChemistryIncludingMedicinal

Chemistry;vol.20;nb.2;(1981);p.114-117

ViewinReaxys

61%,15%Time=0.5h,T=140-160°C

Vaidya,V.P.;Agasimundin,Y.S.;IndianJournalofChemistry,SectionB:OrganicChemistryIncludingMedicinal

Chemistry;vol.20;nb.2;(1981);p.114-117

ViewinReaxys

O

O

O

N

N

NH

2

H

N

O

H

2

N

N

N

N

H

O

N

O

N

NHN

O

OO

N

NH

2

N

Rx-ID:1661085ViewinReaxys40/90

YieldConditions&References

50%,35%inN,N-dimethylacetamide,Time=2h,Heating

Santagati,Maria;Santagati,Andrea;Modica,Maria;Russo,Filippo;Heterocycles;vol.34;nb.5;(1992);p.923-

927

ViewinReaxys

35%,50%inN,N-dimethylacetamide,Time=2h,Heating

Santagati,Maria;Santagati,Andrea;Modica,Maria;Russo,Filippo;Heterocycles;vol.34;nb.5;(1992);p.923-

927

ViewinReaxys

O

O

O

NH

NH

2

H

N

O

N

H

2

N

N

N

N

H

O

HN

O

N

NHN

O

OO

HN

NH

2

N

Rx-ID:1661632ViewinReaxys41/90

YieldConditions&References

50%,30%inN,N-dimethylacetamide,Time=2h,Heating

Santagati,Maria;Santagati,Andrea;Modica,Maria;Russo,Filippo;Heterocycles;vol.34;nb.5;(1992);p.923-

927

ViewinReaxys

30%,50%inN,N-dimethylacetamide,Time=2h,Heating

Santagati,Maria;Santagati,Andrea;Modica,Maria;Russo,Filippo;Heterocycles;vol.34;nb.5;(1992);p.923-

927

ViewinReaxys

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O

O

O

NH

2

H

2

N

N

O

ONH

2

Rx-ID:9867631ViewinReaxys42/90

YieldConditions&References

Withtoluene-4-sulfonicacidintoluene

Li,Bang-Jing;Jiang,Lin;Liu,Min;Chen,Ying-Chun;Ding,Li-Sheng;Wu,Yong;Synlett;nb.4;(2005);p.603-

606

ViewinReaxys

O

O

O

S

O

O

NH

2

S

N

N

H

2

N

N

S

N

O

O

N

S

O

O

H

2

N

Rx-ID:35670474ViewinReaxys43/90

YieldConditions&References

47%inaceticacid,Time=5h,Reflux

Davood,Asghar;Azimidoost,Leila;Rahmatpour,Somaieh;Amini,Mohn;Nikbakht,Ali;Shafaroodi,Hamed;

Ansari,Abdollah;Iman,Maryam;MedicinalChemistryRearch;vol.22;nb.7;(2013);p.3177-3184,8

ViewinReaxys

O

O

O

N

NH

2

H

N

O

N

H

2

N

N

N

N

H

O

N

O

N

NHN

O

OO

N

NH

2

N

Rx-ID:1661276ViewinReaxys44/90

YieldConditions&References

40%,30%inN,N-dimethylacetamide,Time=2h,Heating

Santagati,Maria;Santagati,Andrea;Modica,Maria;Russo,Filippo;Heterocycles;vol.34;nb.5;(1992);p.923-

927

ViewinReaxys

30%,40%inN,N-dimethylacetamide,Time=2h,Heating

Santagati,Maria;Santagati,Andrea;Modica,Maria;Russo,Filippo;Heterocycles;vol.34;nb.5;(1992);p.923-

927

ViewinReaxys

O

O

O

NH

2

H

2

N

N

O

ONH

2

Rx-ID:1661501ViewinReaxys45/90

YieldConditions&References

45%intetrahydrofuran

Alkhathlan,HamadZ.;Al-Lohedan,HamadA.;Phosphorus,SulfurandSiliconandtheRelatedElements;vol.61;

nb.3.4;(1991);p.367-372

ViewinReaxys

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O

O

O

S

O

O

NH

2

H

N

H

2

N

NHN

O

O

S

O

O

NH

2

Rx-ID:87011ViewinReaxys46/90

YieldConditions&References

Withsulfuricacid,glycerol,T=150°C

Takeda;Maejima;;vol.3;(1952);p.231,232

ViewinReaxys

O

O

O

NH

2

N

O

O

H

2

N

N

O

O

H

2

N

N

O

O

Rx-ID:1661084ViewinReaxys47/90

YieldConditions&References

Withaceticacid,Time=2h,Heating

Ries,UweJ.;Mihm,Gerhard;Narr,Berthold;Haslbach,KaiM.;Wittneben,Helmut;etal.;JournalofMedicinal

Chemistry;vol.36;nb.25;(1993);p.4040-4051

ViewinReaxys

O

O

O

NH

2

H

2

N

N

O

O

H

2

N

Rx-ID:1661093ViewinReaxys48/90

YieldConditions&References

38%intetrahydrofuran,Heating

Alkhathlan,HamadZ.;Al-Lohedan,HamadA.;Phosphorus,SulfurandSiliconandtheRelatedElements;vol.63;

nb.3/4;(1991);p.301-305

ViewinReaxys

O

O

ONH

2

H

N

H

2

N

N

O

O

NH

H

2

N

Rx-ID:1661315ViewinReaxys49/90

YieldConditions&References

43%Time=0.5h,T=145°C

Granados,R.;Alvarez,M.;Valls,N.;Salas,M.;JournalofHeterocyclicChemistry;vol.20;(1983);p.1271-1275

ViewinReaxys

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N

H

NH

2

H

2

N

O

O

O

N

O

O

NH

NH

2

2,7-diphthalimido-carbazole

Rx-ID:5553105ViewinReaxys50/90

YieldConditions&References

Withwater,T=190°C

Porai-Koschiz;Saljamon;ZhurnalObshcheiKhimii;vol.14;(1944);p.1019,1021;;<1945>4599

ViewinReaxys

O

O

O

NH

2

H

2

N

N

O

O

NH

2

N

O

O

N

O

O

Rx-ID:86364ViewinReaxys51/90

YieldConditions&References

Withxylene,undErhitzendesvomLoesungsmittelbefreitenReaktionsgemischesauf190grad

Barnes;Godfrey;JournalofOrganicChemistry;vol.22;(1957);p.1043

ViewinReaxys

O

O

O

NH

2

H

2

NN

O

O

H

2

N

Rx-ID:87056ViewinReaxys52/90

YieldConditions&References

Withwater

Koller;ChemischeBerichte;vol.37;(1904);p.2882

ViewinReaxys

Kuhn;Jacob;Furter;JustusLiebigsAnnalenderChemie;vol.455;(1927);p.255

ViewinReaxys

Porai-Koschiz;Mostrjukow;ZhurnalObshcheiKhimii;vol.10;(1940);p.629,634;;(1940);2026

ViewinReaxys

O

O

O

H

2

N

NH

2

NH

2

H

2

N

N

N

N

NH

2

O

O

O

O

O

O

Rx-ID:85858ViewinReaxys53/90

YieldConditions&References

Lamberton;AustralianJournalofChemistry;vol.12;(1959);p.106

ViewinReaxys

Withsodiumacetate,aceticacid

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Lamberton;AustralianJournalofChemistry;vol.12;(1959);p.106

ViewinReaxys

O

O

O

NH

2

H

2

N

N

O

O

NH

2

Rx-ID:86141ViewinReaxys54/90

YieldConditions&References

Withwater

Novelli;AnalesdelaRealSociedadEspanoladeFisicayQuimica;vol.27;(1929);p.750,752

ViewinReaxys

WithN,N-dimethyl-aniline

Porai-Koschiz;ZhurnalObshcheiKhimii;vol.14;(1944);p.1010,1016;;(1945);p.4599

ViewinReaxys

O

O

O

NH

2

H

2

N

N

O

O

H

2

N

Rx-ID:86311ViewinReaxys55/90

YieldConditions&References

Withwater

Kaufler;Karrer;ChemischeBerichte;vol.40;(1907);p.3264

ViewinReaxys

Kuhn;Jacob;Furter;JustusLiebigsAnnalenderChemie;vol.455;(1927);p.255

ViewinReaxys

O

O

O

HN

O

NH

2

H

2

N

ClHN

O

O

HN

O

NH

2

Rx-ID:86613ViewinReaxys56/90

YieldConditions&References

Withwater,sodiumacetate,aceticacid

Protopopescu;Popovici-Stancovici;;vol.1;(1949);p.885,886,889;;(1952);p.945

ViewinReaxys

Withethanol,water

Banerjee;JournaloftheIndianChemicalSociety;vol.12;(1935);p.4

ViewinReaxys

O

O

O

NH

2

H

2

N

N

O

O

H

2

N

N

O

O

N

O

O

Rx-ID:87057ViewinReaxys57/90

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YieldConditions&References

WithN,N-dimethyl-aniline

Porai-Koschiz;Wertkina;ZhurnalObshcheiKhimii;vol.14;(1944);p.365,378;;(1945);p.4068

ViewinReaxys

Withwater

Guglialmelli;Chanussot;Ruiz;BulletindelaSocieteChimiquedeFrance;vol.<4>51;(1932);p.80

ViewinReaxys

Withbenzene

Guglialmelli;Chanussot;Ruiz;BulletindelaSocieteChimiquedeFrance;vol.<4>51;(1932);p.80

ViewinReaxys

O

O

O

NH

2

H

2

N

N

O

O

H

2

N

N

.

N;N'.N'-diphthalyl-m-phenylenedia‐

mine

Rx-ID:5738820ViewinReaxys58/90

YieldConditions&References

Biedermann;ChemischeBerichte;vol.10;(1877);p.1163

ViewinReaxys

Withethanol,sodiumacetate

Meyer,R.;Maier,J.;JustusLiebigsAnnalenderChemie;vol.327;(1903);p.41

ViewinReaxys

O

O

O

NH

2

H

2

NN

O

O

H

2

NN

.

N;N'.N'-diphthalyl-p-phenylenediamine

Rx-ID:5738821ViewinReaxys59/90

YieldConditions&References

Biedermann;ChemischeBerichte;vol.10;(1877);p.1163

ViewinReaxys

Withethanol,sodiumacetate

Meyer,R.;Maier,J.;JustusLiebigsAnnalenderChemie;vol.327;(1903);p.41

ViewinReaxys

S

O

O

NH

2

H

2

NO

O

O

N

O

O

S

O

O

NH

2

Rx-ID:35530298ViewinReaxys60/90

YieldConditions&References

Withaceticacid,Time=24h,Reflux

Al-Suwaidan,IbrahimA.;Alanazi,AmerM.;El-Azab,AdelS.;Al-Obaid,AbdulrahmanM.;Abdel-Aziz,AlaaA.-

M.;Eltahir,KamalE.H.;Maarouf,AzzaR.;AbuEl-Enin,MohamedA.;BioorganicandMedicinalChemistryLetters;

vol.23;nb.9;(2013);p.2601-2605,5

ViewinReaxys

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O

O

O

NH

2

H

2

N

N

O

O

NH

2

Rx-ID:86036ViewinReaxys61/90

YieldConditions&References

Withwater

Fairfulletal.;JournaloftheChemicalSociety;(1952);p.4700,4703

ViewinReaxys

Sako;;vol.6;(1931);p.307,320

ViewinReaxys

O

O

O

NH

2

H

2

N

N

O

O

H

2

N

Rx-ID:86569ViewinReaxys62/90

YieldConditions&References

Withnitrobenzene

Funke;Kirchmayr;Wolf;MonatsheftefuerChemie;vol.51;(1929);p.226

ViewinReaxys

O

O

O

N

O

O

NH

2

N

H

2

N

O

O

N

O

O

N

O

ON

NH

2

O

O

Rx-ID:86583ViewinReaxys63/90

YieldConditions&References

Withwater

Cain;Coulthard;Micklethwait;JournaloftheChemicalSociety;vol.103;(1913);p.2080

ViewinReaxys

T=140-150°C

Cain;Coulthard;Micklethwait;JournaloftheChemicalSociety;vol.103;(1913);p.2080

ViewinReaxys

O

O

O

NH

2

H

2

N

N

O

O

NH

2

Rx-ID:1661005ViewinReaxys64/90

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YieldConditions&References

indichloromethane,Time=5h

Sato,Yasuhiko;Nakai,Hideo;Wada,Masao;Mizoguchi,Tomishige;Hatanaka,Yasumaru;Kanaoka,Yuichi;

Chemical&PharmaceuticalBulletin;vol.40;nb.12;(1992);p.3174-3180

ViewinReaxys

O

O

O

NH

2

H

2

N

N

O

ONH

2

Rx-ID:4150325ViewinReaxys65/90

YieldConditions&References

inaceticacid,Heating

Poupaert,JacquesH.;Hamoir,Gaetane;Barbeaux,Philippe;Lambert,Didier;Henichart,Jean-Pierre;Journal

ofPharmacyandPharmacology;vol.47;nb.1;(1995);p.89-91

ViewinReaxys

O

O

O

O

O

NH

2

H

2

N

N

O

O

OO

NH

2

Rx-ID:85917ViewinReaxys66/90

YieldConditions&References

Withwater

Kaufler;Borel;ChemischeBerichte;vol.40;(1907);p.3253

ViewinReaxys

O

O

O

NH

2

H

2

N

N

O

O

H

2

N

Rx-ID:86179ViewinReaxys67/90

YieldConditions&References

Withethanol

Biedermann;ChemischeBerichte;vol.10;(1877);p.1163

ViewinReaxys

O

O

O

NH

2

H

2

N

N

O

O

NH

2

Rx-ID:86195ViewinReaxys68/90

YieldConditions&References

T=250°C

Porai-Koschiz;Bodik;ZhurnalObshcheiKhimii;vol.15;(1945);p.245,247;;(1946);p.2132

ViewinReaxys

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O

O

O

NH

2

H

2

N

NH

HN

O

O

O

O

N

O

O

HN

NH

2

O

O

NH

O

O

Rx-ID:86593ViewinReaxys69/90

YieldConditions&References

Withwater

Fairfulletal.;JournaloftheChemicalSociety;(1952);p.4700,4703

ViewinReaxys

O

O

O

S

O

O

NH

2

N

N

NH

2

H

2

N

N

O

ON

N

N

O

O

S

O

O

H

2

N

E

Rx-ID:87091ViewinReaxys70/90

YieldConditions&References

Withaceticacid

Wanag;Veinbergs;ChemischeBerichte;vol.76;(1943);p.479,482,483

ViewinReaxys

O

O

O

NH

2

H

2

N

N

O

O

H

2

N4,4'-diphthalimido-biphenyl

Rx-ID:5605560ViewinReaxys71/90

YieldConditions&References

WithN,N-dimethyl-aniline

Porai-Koschiz;Wertkina;ZhurnalObshcheiKhimii;vol.14;(1944);p.365,378;;(1945);p.4068

ViewinReaxys

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O

O

O

NH

2

H

N

O

H

2

N

N

N

H

N

O

O

NHN

O

OO

NH

2

Rx-ID:3947715ViewinReaxys72/90

YieldConditions&References

inN,N-dimethylacetamide,Time=3h,Heating

Russo,F.;Santagati,A.;Santagati,M.;Farmaco,EdizioneScientifica;vol.37;nb.11;(1982);p.719-727

ViewinReaxys

O

O

O

NH

2

H

N

O

H

2

N

Br

N

N

N

H

O

OBr

NHN

O

OO

NH

2

Br

Rx-ID:3947719ViewinReaxys73/90

YieldConditions&References

inN,N-dimethylacetamide,Time=3h,Heating

Russo,F.;Santagati,A.;Santagati,M.;Farmaco,EdizioneScientifica;vol.37;nb.11;(1982);p.719-727

ViewinReaxys

O

O

O

NH

2

H

N

O

H

2

N

I

N

N

N

H

O

OI

NHN

O

OO

NH

2

I

Rx-ID:3947734ViewinReaxys74/90

YieldConditions&References

inN,N-dimethylacetamide,Time=3h,Heating

Russo,F.;Santagati,A.;Santagati,M.;Farmaco,EdizioneScientifica;vol.37;nb.11;(1982);p.719-727

ViewinReaxys

O

O

O

NH

2

H

2

N

N

O

O

H

2

N

N

.

N'--di-phthali‐

mide

Rx-ID:5738517ViewinReaxys75/90

YieldConditions&References

Biedermann;ChemischeBerichte;vol.10;(1877);p.1163

ViewinReaxys

Patent;GeigyandCo.;DE126964;riezweige;vol.6;p.757

ViewinReaxys

O

O

O

O

NH

2

H

2

N

N

O

OO

NH

2

Rx-ID:86308ViewinReaxys76/90

YieldConditions&References

Schiff;JustusLiebigsAnnalenderChemie;vol.218;(1883);p.192

ViewinReaxys

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O

O

O

NH

2

H

2

N

N

O

O

H

2

N

N

O

ON

O

O

Rx-ID:86180ViewinReaxys77/90

YieldConditions&References

Biedermann;ChemischeBerichte;vol.10;(1877);p.1163

ViewinReaxys

O

O

O

H

2

N

O

H

2

N

N

O

O

O

H

2

N

Rx-ID:86830ViewinReaxys78/90

YieldConditions&References

T=160°C

Crippa;Caracci;GazzettaChimicaItaliana;vol.68;(1938);p.109,111

ViewinReaxys

T=160°C

Crippa;Caracci;GazzettaChimicaItaliana;vol.68;(1938);p.109,111

ViewinReaxys

microwaveirradiation

Shemchuk,L.A.;Chernykh,V.P.;Krys'kiv,O.S.;RussianJournalofOrganicChemistry;vol.42;nb.3;(2006);p.

382-387;ZhurnalOrganicheskoiKhimii;vol.42;nb.3;(2006);p.395-399

ViewinReaxys

O

O

O

O

HH

NH

2

H

2

NN

O

O

H

2

N

Rx-ID:5525098ViewinReaxys79/90

YieldConditions&References

Kuhn;Jacob;Furter;JustusLiebigsAnnalenderChemie;vol.455;(1927);p.255

ViewinReaxys

Turner;JournaloftheChemicalSociety;(1932);p.1294

ViewinReaxys

Sircar;Sen-Gupta;lbl.;vol.99;;(1928);p.2247

ViewinReaxys

Koller;ChemischeBerichte;vol.37;(1904);p.2882

ViewinReaxys

LeFevre;Turner;JournaloftheChemicalSociety;(1926);p.2478,2483;JournaloftheChemicalSociety;(1928);p.

249

ViewinReaxys

O

O

O

NH

2

H

2

N

N

O

O

H

2

N

-bis-phthali‐

mide

Rx-ID:5724057ViewinReaxys80/90

YieldConditions&References

GeigyandCo;lbl.;vol.73;nb.I;(1902);p.152

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ViewinReaxys

Patent;GeigyandCo.;DE126964;riezweige;vol.6;p.756

ViewinReaxys

Biedermann;ChemischeBerichte;vol.10;(1877);p.1163

ViewinReaxys

O

O

O

NH

2

H

2

N

N

O

O

H

2

N

-di-phthali‐

mide

Rx-ID:7450584ViewinReaxys81/90

YieldConditions&References

beimZusammenschmelzen

Patent;GeigyandCo.;DE126964;riezweige;vol.6;p.756

ViewinReaxys

Biedermann;ChemischeBerichte;vol.10;(1877);p.1163

ViewinReaxys

O

O

O

NH

2

H

2

N

N

O

O

N

O

O

H

2

N

Rx-ID:86814ViewinReaxys82/90

YieldConditions&References

Funke;Kirchmayr;Wolf;MonatsheftefuerChemie;vol.51;(1929);p.226

ViewinReaxys

O

O

O

NH

2

H

2

N

N

O

O

H

2

N

m-phenylene-bis-phthalimide

Rx-ID:5738341ViewinReaxys83/90

YieldConditions&References

Biedermann;ChemischeBerichte;vol.10;(1877);p.1163

ViewinReaxys

O

O

O

NH

2

H

2

NN

O

O

H

2

Np-phenylene-bis-phthalimide

Rx-ID:5743367ViewinReaxys84/90

YieldConditions&References

Biedermann;ChemischeBerichte;vol.10;(1877);p.1163

ViewinReaxys

O

O

O

NH

2

H

2

NN

O

O

H

2

Np-phenylene-bis-phthalimide

Rx-ID:10600237ViewinReaxys85/90

YieldConditions&References

beimVerschmelzen

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Biedermann;ChemischeBerichte;vol.10;(1877);p.1163

ViewinReaxys

O

O

O

OH

O

–

O

Na

+

NH

2

H

2

N

N

O

O

H

2

N

m-phenylene-phthalimide

Rx-ID:6216189ViewinReaxys86/90

YieldConditions&References

Biedermann;ChemischeBerichte;vol.10;(1877);p.1163

ViewinReaxys

Meyer,R.;Maier,J.;JustusLiebigsAnnalenderChemie;vol.327;(1903);p.41

ViewinReaxys

O

O

O

O

HH

NH

2

H

2

N

N

O

O

H

2

NN

.

N

.

N'.N'-diphthalyl-benzidine

Rx-ID:6216533ViewinReaxys87/90

YieldConditions&References

Kuhn;Jacob;Furter;JustusLiebigsAnnalenderChemie;vol.455;(1927);p.255

ViewinReaxys

O

O

O

OH

O

–

O

Na

+

NH

2

H

2

N

N

O

O

H

2

N

m-phenylene-bis-phthalimide

Rx-ID:5738342ViewinReaxys88/90

YieldConditions&References

Meyer,R.;Maier,J.;JustusLiebigsAnnalenderChemie;vol.327;(1903);p.41

ViewinReaxys

O

O

O

OH

O

–

O

Na

+

NH

2

H

2

N

N

O

O

H

2

Np-phenylene-bis-phthalimide

Rx-ID:5743368ViewinReaxys89/90

YieldConditions&References

Meyer,R.;Maier,J.;JustusLiebigsAnnalenderChemie;vol.327;(1903);p.41

ViewinReaxys

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®andtheReaxys®trademarkareownedandprotectedbyReed

ElvierPropertiesSAandudunderlicen.

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O

O

O

OH

O

–

O

Na

+

NH

2

H

2

N

N

O

O

H

2

Np-phenylene-bis-phthalimide

Rx-ID:10600238ViewinReaxys90/90

YieldConditions&References

Meyer,R.;Maier,J.;JustusLiebigsAnnalenderChemie;vol.327;(1903);p.41

ViewinReaxys