9-Bromo-6,7,8,9-tetrahydro-4//-pyrido

Ester group of l-(ethoxycarbonylmethyl)-7-aryl-5-oxo-1,2,3,5-tetrahydro-pyrido[l,2,3-i/e]quinoxaline-6-carboxamides was hydrolyzed and the 1-carboxymethyl moiety was converted to an aminocarbonylmethyl group with 1-methylpiperazine (01MIP12). Bromo atom of l-(2-bromoacetyl) derivatives was substituted by different amines. An amino group in the side chain attached to the position 1 of 7-aryl-5-oxo-l,2,3,5-tetrahydropyr-ido[l,2,3-i/e]quinoxaline-6-carboxamides was acylated, and terc-butoxycarbonyl protecting group of amino group was eliminated. 

Hexahydro-l,3-diazepin-2-thione may be conveniently converted into the iV,iV -dialkyl-hexa-hydro-l,3-diazepin-2-one by treatment with alkyl halides in the presence of aqueous sodium hydroxide and a catalytic amount of benzyltriethylammonium chloride <82S464> and its reaction with (2-bromo-1 -phenylethylidene)malononitrile affords 7-amino-8-cyano-9-phenyl-2,3,4,5-tetrahydro-pyrido[ 1,2-a][l, 3]diazepine <90JOC4740>. 

Reactions of phenylhydrazine with 6-bromo-6,7,8,9-tetrahydro (128) and 6,6-dibromo-6,7,8,9-tetrahydro- and -1,2,3,4,6,7,8,9-octahydro-l l//-pyrido-[2,1 -6]quinazolin-l Tones (129), and reactions of aryldiazonium chlorides with 6,7,8,9-tetrahydro- and l,2,3,4,6,7,8,9-octahydro-ll//-pyrido-[2,1 -6]quinazolin-l 1 ones (130 and their 6-substituted derivatives (131-133) yielded 6-arylhydrazono-6,7,8,9-tetrahydro- and 1,2,3,4,6,7,8,9-octahy-dro-ll//-pyrido[2,l-6]quinazolin-ll-ones (134) (Scheme 4) (84JHC1301 87JHC1045). 

Nitro-4-oxo-l, 6,7,8-tetrahydro-4/f-pyrido[l, 2-a]pyrimidines 534 (R = 6-, 7-, and 8-Me) or 538 were also obtained from 9-formyl-4-oxo-1,6,7,8-tetrahydro-4i/-pyrido[l,2-a]pyrimidine-3-carboxylates 536 with Clayfen in 24-54% yields (90JOC6198), or from 9-bromo-6-methyl-6,7,8,9-tetrahydro-4//-pyrido[l,2-a]pyrimidin-4-ones 537 with sodium nitrite in 40-62% yields (87H869). From the reaction mixture of 9-formyl-6-methyltetrahydropyridopyrimidine-3-carboxylate 536 (R = 6-Me) both 32% of 9-nitro derivative 534 (R = 6-Me) and 5% of dinitro compound 535 (R = Me) were isolated following column chromatography (90JOC6198). 

N-(3-chloro-5-methoxycarbonylphenyl)-5-bromo-l,2,3,4-tetrahydro-quinoline-8-carboxamide was obtained from 8-bromo-6,7-dihydro-lH,3H,5H-pyrido[3,2,l-z/][3,l]benzoxazine-l,3-dione with methyl 3-amino-5-chlorobenzoate in NMP at 170 °C for 16 h (07WOP2007/028789). 

Bromocyclocarbamation reaction of 2-allyl-l-(terf-butoxycarbonyl)tetra-hydropyridine 94 gave inseparable mixture of 3-epimers of 95 and 96. When a bulky R1 substituent ((Bu) was present in 94 a good level of diastereoselectivity was observed (07EJ02015). Reaction of 2,6-diallyl-tet-rahydropyridine 97 with Boc20, followed by bromocyclocarbamation reaction with NBS, then the treatment of the reaction mixture with KOfBu yielded a mixture of 5- and 7-bromo-3-methylene-tetrahydro-lH-pyrido[l,2-c][l,3]oxazin-l-ones 98 and 99. 

Reaction of 5-bromo-l,2,3,4-tetrahydroquinoline-8-carboxylic acid with COCl2 in THF at room temperature for 16 h gave 8-bromo-6,7-dihy-dro-lH,3H,5H-pyrido[3,2,l-//J[3,lJbenzoxazine-l,3-dione in 80% yield (07WOP2007/028789). 8-Bromo-2-aryl-2,3,6,7-tetrahydro-lH,5H-pyrido [3,2,1-zy]quinazoline-l,3-diones were also prepared in the reaction of N-aryl-5-bromo-l, 2,3,4-tetrahydroquinoline-8-carboxamides and ClC02Ph in boiling 1,2-dichloroethane for 30 min. 

Treatment of 6-bromo-2,3,5,6-tetrahydro-7//-pyrido[l,2,3-de]-l,4-benzoxazine-3,7-dione with NEt3 yielded 2,3-dihydro-7//-pyrido[l,2,3-de]-l,4-benzoxazine-3,7 -dione [70CR(C)1189], Distillation of 6-hydroxy-3,10-dimethyl-3,5,6,7-tetrahydro-2//-pyrido[l,2,3-de]-l,4-benzoxazine from solid KOH gave approximately a 1 1 mixture of 3,5- and 3,7-dihydro-2H derivatives (88GEP3817565 90GEP3936250). 

Bromo-l-[(3,4-dimethoxyphenyl)methyl]-l,2,3,4-tetrahydro-9H-pyrido[3,4-b] indole hydrochloride... 

Tetrahydro-4-oxo-4H-pyrido[l,2-a]pyrimidines contain an active methylene group in position 9, which permits versatile transformations. " Depending on the molar ratio, halogenation of 4-oxo-6,7,8,9-tetra-hydro-4//-pyrido[l,2-fl]pyrimidines gave 9-halo or 9,9-dihalo com-pounds. " 9-Bromo- or 9-chloro-6-methyl-4-oxo-6,7,8,9-tetra-hydro-4H-pyrido[l,2-a]pyrimidine-3-carboxylic acids were obtained as 4 1 mixtures of the thermodynamically more stable 6,9-diaxial and the 6-axial, 9-equatorial-substituted diastereoisomers. ... 

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