Isoquinolines 3-amino

Some substituted unsaturated arylcarbodiimides undergo intramolecular cyclization. For example, the vinyl carbodiimide 63 acts as an azadiene to undergo a 6 7r-electrocycli-zation on heating at 140 °C to form an intermediate, which rearomatizes to give 1-amino-isoquinolines 64." ... 

Pyridinium and quinolinium ylides undergo many of the reactions associated with N-oxides. N-Iminopyridinium ylides, for example, are readily converted into IH-l, 2-diazepines, whereas until recently AMminoquinolinium ylides and analogous isoquinolinium ylides had given only 2-aminoquinolines and 1-amino-isoquinolines, respectively. Irradiation of the iV-iminoquinolinium ylide dimers... 

Chen et al. reported the synthesis of 2-phenylimidazo[2,l-fl]isoquinoline 71 (Scheme 28) by cyclocondensation reaction of a-tosyloxyketones with 1-amino isoquinoline using [BPY][BF4] as solvent in a molar ratio of 1 10 (reactant/IL) at RT in the presence of Na2C03 [141]. The IL was recycled and reused three times with no significant decrease in product 5ueld was noticed. The reaction performed using acetonitrile as a molecular solvent required 5h of refluxing to furnish 71. 

The synthesis of 1-amino-isoquinoline-A-oxides from 2-alkynylbenzaldoxime and related compounds has been achieved using a silver/copper-cocatalyzed reaction in air (Scheme 3.58) [64]. While silver triflate was used as the silver source, a range of copper salts were screened for activity, and copper iodide was found to be an effective cocatalyst... 

SCHEME 3.58 Preparation of 1-amino-isoquinoline-ALoxides from 2-alkynylbenzaldoximes [64]. 

Various heterocyclic compounds have been used as substrates for the Conrad-Limpach reaction. Amino-isoquinoline 52 was converted into 54 in 36% overall yield. ... 

A solution of N-(2-aminobenzyl)-l-phenyl-2-methylaminoethanol-l was prepared by the reaction of a-bromo-acetophenone and (2-nitrobenzyl)methylamine, followed by hydrogenation of the nitro group by means of nickel on diatomaceous earth at room temperature and reduction of the CO group by means of sodium borohydride. The intermediate thus produced was dissolved in 100 ml of methylene chloride and introduced dropwise into 125 ml of sulfuric acid at 10° to 15°C. After a short standing, the reaction mixture was poured onto ice and rendered alkaline by means of a sodium hydroxide solution. By extraction with ether, there was obtained l,2,3,4-tetrahydro-2-methyl-4-phenyl-8-amino-isoquinoline. The base is reacted with maleic acid to give the maleate melting point of the maleate 199° to 201°C (from ethanol). 

Kametani et al. (544,545) and other workers (546-561) endeavored to carry out the synthesis of cularine alkaloids by phenolic oxidation (bio-genetic type of synthesis) of the corresponding derivatives of laudanosine. The paper (549) describes the synthesis of these bases via the 6-ethoxycar-bamido-3,4-dihydroisoquinolines, which were converted to 6-amino-isoquinoline. By Ullmann reaction it gives the compound 52 and ( )-cularine (51) (Scheme 18). Cularine-type alkaloids were also synthesized by the intramolecular Ullmann reaction of 7,8-disubstituted isoquinoline obtained by the usual Bischler-Napieralski reaction from the phenolic bromoamide (pathway a) (544, 548). However, in the papers referred to (557,558,561), the rings A, C, and D were formed first (pathway b), and only then was the ring formed during the synthesis of cularine. 

Morpholino(l-((3-(trifluoromethyl)phenyl) amino)isoquinolin-4-yl)methanone (97) MWI, 100°C, 5min Cannabinoid 2 (CB2) receptor agonist (insignificant) [91]... 

Carbonylation of halides in the presence of primary and secondary amines at I atm affords amides[351j. The intramolecular carbonylation of an aryl bromide which has amino group affords a lactam and has been used for the synthesis of the isoquinoline alkaloid 498(352], The naturally occurring seven-membered lactam 499 (tomaymycin, neothramycin) is prepared by this method(353]. The a-methylene-d-lactam 500 is formed by the intramolecular carbonylation of 2-bromo-3-alkylamino-l-propene(354]. 

Ha.loisoquinolines, The Sandmeyer reaction is commonly used to prepare chloroisoquinolines from the amino compound. The corresponding hydroxy compounds are also used by treatment with chlorides of phosphoms. The addition of bromine to a slurry of isoquinoline hydrochloride in nitrobenzene gives a 70—80% yield of 4-bromoisoquinoline [1532-97-4J. Heating 1-chloroisoquinoline [19493-44-8] with sodium iodide andhydriodic acid gives 1-iodoisoquinoline [19658-77-6] (179). 

In the case of the 2-dimethylamino- (or 2-amino-)methylene derivatives, the products were at first thought to be pyrimido[4,5-c]isoquinolines (267), but later work with 6-(N-substituted amino)uracils assigned the structures of the products (268) as belonging to the isomeric pyrimido[4,5-f>]quinoline system (74CB2537), in agreement with the regioselection rules above. 

The only other synthesis of a benzo fused derivative involves the pyridazino[4,3-cjisoquinoline series, the isoquinoline derivative (377) reacting with hydrazine to give (378) (74YZ607), although an s-triazolo-fused pyrido[2,3-tf Ipyridazine was obtained in the reaction of l-amino-3-iminoisoindolenine with hydrazine and formic acid (56GEP951993). 

The one report of a true [3-1-3] cyclization occurs in the only reported synthesis of the pyrazino[2,3-c]isoquinoline ring system. The isoquinolino fused derivative (451) was isolated from dimerization of an intermediate iminoquinone formed by air oxidation of the unstable 4-amino-2-methyltetrahydroisoquinolin-l-one (450) 75JOC1760). 

Chichibabin reaction, 5, 409-410 UV spectra, 5, 356 Naphthimidazoles, 2-amino-tautomerism, 5, 368 Naphth[2,3-h]imidazoles oxidation, 5, 405 Naphth[l,2-d]imidazolium salts nucleophilic substitution, 5, 412 Naphth[l, 2-h]isoquinolines... 

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