3.4- Dihydro-6,7-dimethoxy-isoquinoline

Isoquinoline, 2-acetyl-l, 2,3,4-tettahydro-6,7-dimethoxy-l-inethylene-, 4 Isoquinoline, 2-benzoyl-l -benzy 1-1-cyano-1,2-dihydro- [1-Isoquinolinecarbo-mtrile, 2-benzoyl-l, 2-dihydro-l -(phenjlmethyl)-), 23 Isoquinoline, 2-benzoyl-l -cyano-1,2-di-hydro l-Isoquinohnecarbomtrile, 2-ben2oyl-l, 2-dihydro-], 20 ISOQUINOLINE, 1-BENZYL- [ISOQUINOLINE, HPHENYLMFTHYL)-], 19 Isoquinoline, 3,4-dihydro-6,7-dimethoxy-l-methyl-, 4... 

Oimethoxy-1 -methyl-3,4-dihydrolsoquinoline Isoquinoline, 3,4-dihydro-6,7-dimethoxy-1-methyl- (8,9) (4721-98-6)... 

Aryloxy-9,10-dimethoxy-6,7-dihydro-4//-pyrimido[6,1 -a]isoquinolin-4-ones formed in the reaction of 2-chloro derivative and phenols in the presence of K2CO3 in DMF at 90 °C for 2. 5 h or in boiling 2-PrOH for 6-24 h (00MIP20). When 2-isobutylphenol was used the reaction was carried out in the presence of BuLi in THF at —78 °C. 

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>. 

The system Ru2(OAc) Cl/O2/toluene/50°C oxidisedR CH NHR to imines R CH=NR converted 1,2,3,4-tetrahydroisoquinoline to the 3,4-dihydroisoquinoline with isoquinoline, and 6,7-dimethoxy-l,2,3,4-tetrahydroisoquinoline to 6,7-dimethoxy-3,4-dihydro-iso-qninoline (cf. mech. Ch. 1) [18], Such oxidations were also catalysed by TPAP/NMO/PMS/CH3CN, e.g. the conversion of indoline to indole (in which indoline nndergoes a donble-bond shift and aromatisation), and the oxidation of 1,2,3,4-tetrahydroqninoline to 3,4-dihydroquinoline (Fig. 5.1, Table 5.1) [19]. 

R,5 S)-2-[(2-bromomethylphenyl)methyl -2,5-dihydro-5-mpropyi-3,6-dimethoxy-2-meth ipyrazme >97% de 6 (3, 11 aR)-3,4,6, t t-tetrahydro-3-isoprop I-l-methoxy-U a-methyl-4-oxopyrctzino[l, 2-b isoquinoline yield 75% 97% de... 

Catalytic hydrogenation of 3,4-dihydro-2//-pyrimido[2,l-a]isoquinoline-2,4-diones (93) and 3,3-diethyl-9,10-dimethoxy-3,4,6,7-tetrahydro-2//-pyrimido[2,l-a]isoquinoline-2,4-dione (94) over Pt02 and Pd/C catalysts gave l,3,4,6,7,llb-hexahydro-2/7-pyrimido[2,l-a]isoquinoline-2,4-diones (95) [69YZ649 71JPP71/09466]. From the mother liquid of compounds 93 (R = H, R1 = Et and R = R1 = Et) 3-ethyl-2-hydroxy-6,7-dihydro-and -8,9,10,1 l-tetrahydro-4//-pyrimido[2,l-a]isoquinolin-4-ones, and 3,3-diethyl-l,3,4,llb-tetrahydro-2//-pyrimido[2,l-a]isoquinoline-2,4-dione, also could be isolated as minor products. Reduction of 3,3-diethyl-l,3,4,6,7,llfo-hexahydro-2//-pyrimido[2,l-a]isoquinoline-2,4-dione (95, R = R1 = Et, R2 = H) with LAH in tetrahydrofuran at 70°C for 9 h afforded 3,3-diethyl-l,3,4,6,7,llb-hexahydro-2//-pyrimido[2,l-a]isoquinoline (96). 

To a stirred solution of 6,7-dimethoxy-l,2,3,4-tetrahydroisoquinoline (3.00 g, 15.4 mmol, 1.00 equiv.) in anhydrous pyridine (100 mL) under argon at room temperature was added acetic anhydride (14.5 mL, 154 mmol, 10.0 equiv.) over 15 min. The resulting mixture was stirred at room temperature for 2 h, and then at reflux for 6 h. The volatiles were removed by rotary evaporation at 80°C under high vacuum. The residue was flash chromatographed on silica gel (MeOH-CH2CI2 8 92) to afford 3.21 g (89%) of l-(6,7-dimethoxy-3,4-dihydro-lH-isoquinolin-2-yl)ethanone as a viscous brown oil. The H-NMR spectrum reflected the presence of two slowly interconverting conformers in a ratio of 1.2 1 at room temperature. 

Synthesis of 2-[l-(6,7-dimethoxy-3,4-dihydro-lH-isoquinolin-2-yl)ethylidineamino]-4,5-dimethoxybenzonitrile ... 

To a solution of 2-(6,7-dimethoxy-3,4-dihydro-lH-isoquinolin-2-yl)-6,7-dimethoxyquinolin-4-ylamine (150 mg) in hot CH2CI2 (4.5 mL) and MeOH (1.5 mL) was added a solution of fumaric acid (22.8 mg, 0.196 mmol, 0.50 equiv.) in hot MeOH (3.0 mL). The resulting mixture was concentrated and the product was recrystallized from MeOH with hot filtration to afford, after filtration, 85 mg of light brown solid m.p. 239-240°C. 

Chemical Name 2-[(l,l-Dimethylethyl)amino]-6,7-dihydro-9,10-dimethoxy-4H-pyrimido[6,l-a]isoquinolin-4-one... 

A solution of 9,10-dimethoxy-2-chloro-6,7-dihydro-4H-pyrimido[6,l-a]isoquinolin-4-one (3.0 g) and t-butylamine (10 ml) in chloroform (75 ml) is heated under reflux for 16 h. The solvent is evaporated under reduced pressure and the residue triturated with a dilute solution of sodium hydroxide to give a white precipitate of 9,10-dimethoxy-2-t-butylamino-6,7-dihydro-4H-pyrimido[6,l-a]isoquinolin-4-one. 

Synthesis of 3-benzylamino-8,9-dimethoxy-5,6-dihydro[5,1-a] isoquinoline[5-14C] hydrochloride 199... 

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