L- isoquinolines

R" = CH20H). The use of sodium borohydride in place of lithium aluminum hydride did not lead to ring closure but to 3-[j8-(A-l,2,3,4-tetrahydroisoquinolyl)ethyl]indole derivatives (53). Reductive cyclization by means of lithium aluminum hydride of the j8-(3-indolyl)ethyl-l-isoquinoline (52) to the pentacyclic tetrahydro-j8-carboline 49 (R = R = R" = H) has been reported. Strong acid alone sufficed to convert 52 into 54, the 0x0 derivative of 49. ... 

Ethyl 1 -phenyl-1,8b-dihydroazirino[2,l- ]isoquinoline-3-carboxylate (2), obtained by decomposition of azide 1 (see Section 3.2.1.1.1.1.) in the presence of triethyl phosphite, on heating under reflux in toluene, rearranges quantitatively to the 3//-3-benzazepine 3.82... 

The Rh-catalysed asymmetric hydrosilylation of prochiral ketones has been studied with complexes bearing monodentate or heteroatom functionalised NHC ligands. For example, complexes of the type [RhCl(l,5-cod)(NHC)] and [RhL(l,5-cod)(NHC)][SbFg ], 70, where L = isoquinoline, 3,5-lutidine and NHC are the chiral monodentate ligands 71 (Fig. 2.11). 

Cyano-4-hydroxypyridazino[l,6- ]quinolinium betaine 67 could be isolated from the reaction mixture of 1-amino-2-ethoxycarbonylquinolinium mesitylensulfonate and acrylonitrile in a few percent. Reaction of the 2-amino-1-ethoxycarbonylisoquinolinium salt with acrylonitrile afforded only a pyrazolo[5,l- ]isoquinoline derivative. 

Conformational studies of cis-A, b-H- and /ra r-6,llb-/7-6-methyl-2,3,4,6,7,llb-hexahydro-l/7-pyrimido[6,l- ]-isoquinolin-2-ones 89 and 90 by means of the MM2 method as implemented in HyperChem 4.5 suggested that in the lowest-energy conformations the heterocyclic moiety adopted /ram-fused ring annelation in both cases, with a pseudoequatorial and axial methyl group, respectively <1997LA1165>. 

Cyclization occurred at the N-3 atom when 4-(3-bromopropylaruino)-l, 6,7,1 1 b-tctrahydro-2//-pyrimido[6,l -zz -isoquinoline was treated with NaH to give a tetracyclic derivative <2003M1271>. 9,10-Dimethoxy-2-(arylimino)-2,3,6,7-tetrahydro-4//-pyrimido[6,l- ]isoquinolin-4-ones were N-3-alkylated with iV-(ra-bromoalkyl)phthalimides in the presence of K2C03 and a catalytic amount of I2 in boiling 2-butanone in 13-67% yields <2000W020/058308>. Treatment of the 2-[(4-methoxyphenyl)methyl] derivative of 2,3,6,7-tctrahydro-l //,5//-pyrido[3,2,l-/ylqninazolinc-... 

Heating 2-(arylaminothiocarbonyl)-T(2-hydroxyethyl)-l,2,3,4-tetrahydroisoquinolines in EtOH in the presence of HC1 afforded 4-arylimino-l,6,7,llb-tetrahydro-2/7,477-[l,3]thiazino[4,3-tf]isoquinolines <2001ARK33>. 1,3,4,6,7,11b-Hexahydro-2/7-pyrimido[6,l-+]isoquinoline-2,4-diones were obtained by the cyclization of 2-(2-aminocarbonyl-l,2,3,4-tetrahydroisoquinolin-l-yl)acetates on the action of a base <2004MOL694>. 

Reaction of 2-cyanomethylpyridine with iV-(l-aryl-l-chloro-2,2,2-trifluoroethyl)-iV -(4-methylphenyl)carbodiimides, and with (1,1,2,2,2-pentachloro- and l,l-dichloro-2,2,2-trifluoroethyl)isocyanates or A-methoxycarbonyl-l,2,2,2-tetrachloro-, — l-chloro-2,2-trifluoroacetaldehyde imines afforded 3-aryl-4-cyano-l-(4-methylphenyl)imino-3-trifluoromethyl-2,3-dihydro-17/-pyrido[l,2-f]pyrimidines and 4-cyano-3-trichloro-, 4-cyano-3-trifluoro-17/-pyrido[l,2-4pyrimidin-l-ones, respectively <2004CHE47>. Refluxing 2-cyanomethylpyridine and iV-(l-aryl-l-chloro-2,2,2-trifluoroethyl)isocyanates in benzene furnished l-aryl-4-cyano-l-trifluoromethyl-l,2-dihydro-3//-pyrido[l,2-4pyrimidin-3-ones. However, when the solution of the isocyanate was added dropwise to the solution of 2-cyanomethylpyridine, and the reaction mixture was then treated with NEt at room temperature, the isomeric 3-aryl-4-cyano-3-trifluoromethyl-2,3-dihydro-l//-pyr-ido[l,2-dpyrimidin-l-ones were obtained. Reaction of l-(acetyl- and benzoylmethylene)-6,7-dimethoxy-l,2,3,4-tetra-hydroisoquinolines with PhCONCS yielded 1-acetyl-, 1 -benzoyl-9,10-dime thoxy-3-pheny 1-6,7-dihydro-2//-pyrimido[6,l- ]isoquinoline-2-thiones <2003SL2369>. 

Reaction of iV-aminocarbonyl-2-phenylethylamines with mesityl oxide and 2-butenal afforded l,2,3,6,7,llb-hexahydro-477-pyrimido[6,l- ]isoquinoline-4-ones <2003MC278>. 9,10-Dimethoxy-l,2,3,6,7,llb-... 

Ethyl l-(arylimino)-l//-pyrido[l,2-c]pyrimidine-3-carboxylates exhibited anti-inflammatory activities in the carrageenan mouse paw edema model <2001JME1011>. 2-Arylimino-2,3,6,7-tetrahydro- <2000W020/058308> and 2-aryloxy-6,7-dihydro-477-pyrimido[6,l- ]isoquinolin-4-ones <2000W020/0558309> were patented as PDE inhibitors and as useful agents for treatment of respiratory disorders, respectively. 

Benzo[g]cycl[3.2.2]azines or pyrrolizino[3,4,5- 3]isoquinolines, for example, 366, are similarly obtained by cycloaddition of DMAD to pyrrolo[2,l- ]isoquinolines <1985CPB3038>, and l-aza-benzo[ ]cycl[3.2.2]azines are prepared by cycloaddition of DMAD to imidazo[2,l- ]iso-quinolines <1985H(23)2531> (Scheme 102). In all of the above cases, as with the simpler cyclazines, the ester functions are removable by hydrolysis in aqueous alkali followed by... 

In fact, a single series of phosphorus-based heterocyclic compounds, l,3-azaphospholo[5,l- ]isoquinolines (435 X = P), was reported together with their preparation through 1,5-electrocyclization of bis-(A-pyridinium ylidyl)phos-phenium chlorides 437, as shown in Scheme 113 <1999TL1565>. 

Extension of these studies to benzologues of tetrazolo[l,5- ]pyridine, that is, for tetrazolo[l,5- ]quinoline 21 and tetrazolo[5,l- ]isoquinoline 22, led to interesting results <2003JOC1470> as shown in Scheme 7. Both of these fused tetrazoles resulted in formation of a nitrene 23 and 24, respectively, which could be interconverted via formation of the fused cyclic carbodiimide derivative 25. Isoquinolylnitrene 24, furthermore, was found to undergo subsequent reactions ring opening afforded the vinylnitrene 26, which was transformed to o-cyanophe-nylacetonitrile 27 by a 1,2-H shift and to 4-cyanoindole 28 by an intramolecular cyclization in 40% and 25% yields, respectively. 

A novel methodology for cyclization to partially reduced tetrazolo[5,l- ]isoquinolines has been elaborated by Ek et al. <2003T6759> as shown in Scheme 29. The key step is the iodocyclization of an allylphenyltetrazole compound 124 - conveniently synthesized from the appropriate allyl-substituted benzonitrile 123 - under very mild conditions (iodine, acetonitrile solution, 0°C, 3h) to give the iodomethyl-substituted product 125. 

The reaction of 1-aminoisoquinolines and EMME by heating in boiling DMF for 18 hr yielded pyrimido[2,l- ]isoquinoline-3-carboxylates (1059) (85EUP143001). 

Nitrosation of 2-amino-4//-pyrimido[2,l-u]isoquinolin-4-ones (151, R1 = H) in acetic acid with sodium nitrite at 70°C gave 2-amino-3-nitroso derivatives (151, R1 = NO) (73GEP2261009). Bromination of 2-methyl-4//-pyrimido[2,l- ]isoquinolin-4-one (32 = Me) with N-bromosuccin-imide in boiling chloroform for 1 h yielded 3-bromo derivative 152 in 96% yield (80KGS1656). 

Flash vacuum pyrolysis of 357 (R = H, Me) at 530°C/0.01 mmHg gave imidazo[2,l-a]isoquinolines (368) with only traces of other products provided that the sublimation temperature was maintained about 25 °C below the melting point (92AJC1811 93T8147). If compounds 357 (R = H) were allowed to melt during the flash vacuum pyrolysis, or if the pyrolysis was carried out in the condensed phase, a number of products was obtained ethyl 2-hydroxy-4-oxo-4//-pyrimido[2,l- ]isoquinoline-3-carboxylate (20) was a major component (93T8147). 

Mdrour synthesized a series of indolo[2,l- ]isoquinolines and pyrrolophenanthridines via Heck cyclizations onto the C-2 and C-7 positions of indole, respectively [274]. Two examples are shown. 

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