Synthesis of Isoquinolines Bearing Differentially Functionalized Nitrogen Substituents at Positions 3 and 4 through Amine Displacement on a 4-Nitro-3-(p-toluenesulfonyloxy)isoquinoline
✍ Scribed by Jeffery S. Hinkle; O.William Lever Jr.
- Publisher
- Elsevier Science
- Year
- 1988
- Tongue
- French
- Weight
- 713 KB
- Volume
- 44
- Category
- Article
- ISSN
- 0040-4020
No coin nor oath required. For personal study only.
✦ Synopsis
Absrracf. A mtbod fa tbc synthesis of imquinolina functionalizcd with diffuwIti4tcd niOogaI ruktituaus u posilions 3 and 4 is &xribal. -flu amhod iwoks kxyiatia~ of l 3.hydmxy4niuoisoquincUe ud su&qqnt tmyke displ~~~~~~t by amine nuckopbiks to give 3-aminH-nitroisa@oline &aivariws. Ihe pm&co of XV c c-o bead ckavlge. RcductionoftbcQai~oOrarpud~ddK~sultingC~aroieypwiderbK. atntia&IudCamino zxr+ily rvxilabk by otbcr methods. Approprirtely substituted compounds a~ amuubk to further m by thcir.am vasion b im&zo(5.4-c]isaqu daivxeva. AdditicA studies on the tosykr displacawt in&atatfhudliolll+mnultxlsooccMby Xi.uiondIheCObcuiaDgivcr3-lhioakrdaivuive.and that zcutiom of the 4-nimt3-rosyloxyisoqui.noline system with anain olha nuckophiks. including alcohols. did no1 procded WY. Webaumcinaatsledinchesp~sotI~isoquioolinedaivlrivtrrr~dm~in~tigrtiondisoquim(ine coaqou&~ginmcsIingphpnrwlogicxlrtivily. xnpueular,wefcquimdwarstor ¶criuof~indints1 f~arithdiff~riucdniaogcnurbrtihwnu~poritiau~ud4. TIbCSecoqmndsrrefuninoiso6IauofaIr 4.substitured isoquinolin-3-01 (2) cudiovascular agents. 'Mdmayalsoscweasinccmaadirtutorvxrictyofothcr hacmcycks~poaatialintewinclwiing~sysems(3). A&cwofbwiibnnueindifuedthatbKnquisi~~&xCno iso+noliocs have not bun well dcsuibcd, in spite of Ihc signifiiam body of cheolistry rqxmcd oa the ubiquitous isoquinolinc ring system,2 In fact. synthetk qats of isaquinoliis S~bShNtd al both the 3-and Cpodions with nitrogen func&maliry (1) include only axnpoun& also ammining hetemtom substitucna xt the I-positiocl (oxygen.3 nioogcn' or halogenj). The synthetic methodologies employed in the% reports were not useful for the preparation of our mrget compounds 1. We thnefac sought I pmcticti method to produce 3.4-dimino isoquinolim derivatives with a key rcquirrmnt mat our synthetic snatcgy include the tility to diffmntiate ktwcn Ihe 3 and 4 nimgcn s~bstituenu fa further ehbuadon. NW3 R"/NLJ 1 Y-NRJQ 2 Y = OH: X = 6.7-(OMch: RI -Me 3 hn xmwtivc apprwch to our farget cc4npounds involved tJe prrprntion of 4-nitmisoquinoline duivuiva bcafing a krving gIWpUlbC3-pOSi&XWbiChC#lkibCdiSplmdbyrrriau~ ThiswouldpnJvi&3-amiJKAniuoaMbgsandpc7mil ~tioabawanrbt3~4~rrogensubstiDnnabmru%rabctpnoCt&~nierograrpmdrubssgutntek~donof tbc Qanino flmctiw. we initially amtemplucd using ctlkne n the kwing @Dup. but dircovaed fhu 3&kXe4-niuo. isog~arctire&iiyobminuL Facxampk,3-chkdroquinolin~ni~ubr+pairioarrihcrhar he duid 4position.6 Fudumozr. dhough 3-bydroxy4nim~isoquine 6 is readily rvtikbk by niuwion of 4 ~1
tDobioad~RofcssaEdwudC.T~ylaontkouxioo of his 65th birddry.
2.99 (s, 3H); LRMS @CT). dr (rel.