4- Chloro-6,7-dihydro-5//-pyrimido

Reaction of 2-chloro-6,7-dihydro-4//-pyrimido[6,1 -a]isoquinolin-4-ones with liquid NH3 in a pressure bomb at 85 °C for 4h, and with primary and secondary amines in boiling CHCI3 (98MIP15), and anilines in boiling i-PrOFI (00MI17) yielded 2-amino-6,7-dihydro derivatives or their 2,3,6,7-tetrahydro-2-imino tautomers. 

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>. 

Reaction of pyridines with dialkyl acetylenedicarboxylates in the presence of isocyanates in dry CH2C12 at room temperature produced 1-substituted 2-oxo-l,9a-dihydro-2/7-pyrido[l,2-tf]pyrimidine-3,4-dicarboxylates <2004TL1803>. One-pot, three-component synthesis of 1-substituted 2-oxo-l,llb-dihydro-2//-pyrimido[2,l- ]iso-quinoline-3,4-dicarboxylates and 4-(3-chloro-4-methylphenyl)-3-oxo-4,4a-dihydro-3/7-pyrimido[l,2-tf]quinoline-l,2-dicarboxylate was realized by the reaction of isoquinoline and quinoline with isocyanates and dialkyl acetylenedicarboxylates <2004S861>. Diastereomeric mixtures of l-tosyl-2-aryl-l,llb-dihydro-2/7-pyrimido[2,Ttf]isoquinoline-3,4-dicarboxylates were obtained from isoquinoline, iV-tosyl-benzaldehyde imines, and DMAD <2002OL3575>. 

Benzyl-9-phenyl-3,4-dihydro-27/,677-pyrimido[6,l-A [l,3]thiazine-6,8-(7//)-dione was prepared from 3-benzyl-6-chloro-l-(3-chloropropyl)-5-phenylpyrimidine-2,4-(17/,3//)-dione and NaSH hydrate in DMF in 27% yield <1995W035296>. 

L-Tryptophan was used for the synthesis of octahydroindolo[2,3-a]quinol-izines 147 (64CB2463 74CPB2614 81JOC4914), and the tetracyclic system 148 was obtained from a-AAs and 4-chloro-6,7-dihydro-5//-pyrimido[5,4-d][l]benzazepine (93JHC233). 

Catalytic hydrogenation of 6-chloro-8-nitro-3,4-dihydro-2//-pyrimido-[l,2-a]isoquinoline in ethanol over Pt02 for 69 h afforded 8-amino-3,4-di-hydro-2H-pyrimido[l,2-a]isoquinoline (67IJC403). 

The amino groups of isomeric 5-aminomethyl-8-chloro-6-phenyl-3-methyl-l-oxo-1/7- and -l-methyl-3-oxo-3//-pyrimido[l,2-a]quinolines were acylated with acetic anhydride at room temperature for 1 h (79CPB2927). 5,8,9-Trihydroxy-2,3-dihydro-l//-pyrimido[l,2-a]quinoline-l-carboxylic acid was acylated with acetic anhydride in pyridine at room temperature for 24 h (87T2261). 

Whereas cyclization of 2-(3-chloropropionamido)quinolines (210) afforded 2,3-dihydro-l//-pyrimido[l,2-a]quinolin-3-ones (211), an attempted thermal cyclization of ethyl 3-[(2-quinolyl)amino]propionate (212) gave only 2-amino-6-chloro-4-phenylquinoline-3-nitrile (73YGK313). 

Cyclization of l-(3-hydroxypropylamino)isoquinolines (234) in boiling phosphoryl chloride for 3 h (67IJC403) or on the action of thionyl chloride (72GEP2206012 72SAP72/01118) gave 3,4-dihydro-2tf-pyrimido[2,l-a]-isoquinolines (235). Cyclization of l-(cyclopropylamino)-7-chloro-3,4-dihydroisoquinoline yielded 10-chloro-3,4,6,7-tetrahydro-2//-pyrimido[2,l-a]isoquinoline (69GEP1911519). 

V-(2-Arylethyl)ureas (405) and malonic acid in phosphoryl chloride at 105-110°C gave 2-chloro-6,7-dihydro-4//-pyrimido[2,l-a]isoquinolin-4-ones (406) (81GEP3006478 90T1323). 

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. 

Related Reagents. 7-Chloro-l,2-dihydro-2-phenyl-imidazo [l,2-a]quinoline (Cl-PIQ), / -Enantiomer [863319-04-4]) 3,4-Dihydro-2-phenyl-2//-pyrimido[2, l-fi]benzothiazole (HBTM) 2-(A -Benzyl-7V-methylaminomethyl)- 1-methylpyrrolidine (/ -Enantiomer [540474-12-2], 5-Enantiomer [208833-00-5]) 4-Dimethylaminopyridinyl(pentaphenylcyclopentadienyl)rron (C5 Phs-DMAP, / -Enantiomer [187682-64-0], 5-Enantiomer [187596-69-6]). ... 

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