Perhydropyrido pyrazines

Racemic or optically active perhydropyrido[l,2-a]pyrazines were obtained by reduction of 9a5-perhydropyrido[l,2-u]pyrazin-4-one with LAH in Et20 at room temperature (99H(51)2065) and by reduction of perhydropyr-ido[l,2-u]pyrazine-l,4-diones with LAH in boiling THF (97USP5703072, 00JAP(K)00/86659). Treatment of (9uS)-2-(fcrf-butoxycarbonyl)perhydro-pyrido[l,2-u]pyrazin-4-one with LAH in Lt20 afforded (9uS)-2-fcrf-butox-ycarbonyl-l,6,7,8,9,9a-hexahydro-2//-pyrido[l,2-a]pyrazine (99H(51)2065). 

Reduction of a 7-(2-oxoethyl) derivative with NaBH4 in EtOH at room temperature gave 7-(2-hydroxyethyl)-2-(2-pyrimidinyl)perhydropyrido[l, 2-u]pyrazine (99MIP6). Reduction of 7-formyl-8-[(4-cyanophenyl)methoxy]-1,3,4,6,11,1 lu-hexahydro-2//-pyrazino[l,2-A]isoquinoline-l,4-dione with NaBH4 yielded a 7-hydroxymethyl derivative (98MIP7). 

Methyl 2-substituted perhydropyrido[l,2-u]pyrazine-8-acetates were obtained by catalytic hydrogenation of 2-substituted 8-(methoxycarbonyl-methylene)perhydropyrido[l,2-a]pyrazines over 10% Pd/C catalysts (00JAP(K)00/86659). A side chain 4-pyridyl group was hydrogenated over Pt02 catalysts to yield a 4-piperidyl derivative. 

Substituted perhydropyrido[l,2-n]pyrazines were reacted with 2-fluorobenzohydroximinoyl chlorides in the presence of DBU in CHCI3 to yield a isomeric mixture of 7-substituted 2-[(hydroxyimino)phenylmethyl]-perhydropyrido[l, 2-u]pyrazines (99MIP9). 

Benzo[i/]isoxazol-3-yl)perhydropyrido[ 1,2-u]pyrazines were obtained by the cyclization of 2-[(hydroxyimino)phenylmethyl]pyrido[l,2-u]pyrazines on the action of NaH in THF at 90 °C for 18 h (99MIP9). 

Acetyl-3-(perhydropyrido[l, 2-u]pyrazin-2-yl)-1 //-indole was deacety-lated in boiling MeOH in the presence of NaOH, and the product, 3-(perhydropyrido[l,2-u]pyrazin-2-yl)-l//-indole was N-acylated with different arylsulfonyl chloride in THF at 0°C in the presence of (Me3Si)2NNa (99MIP12, 01USP6251893)). 

Hydroxy group of rru -7,9u-H-7-(prepared from 7-formyl-2-(2-pyrimidyl)perhydropyrido[l,2-u]pyrazine by the treatment with MeOCH2P(Ph)3Cl in the presence of -Pr2NH in THF at 0°C, than with BuLi at room temperature (99MIP6). 

Hydroxy group of 8-hydroxy-3-(4-methoxyphenylmethyl)-2-[4-(l-rerr-butoxycarbonyl-4-piperidinyl)butyl]perhydropyrido[l,2-a]pyrazine was alkylated with /err-butyl chloroacetate (00JAP(K)00/86659). 

A side chain carboxyl group in perhydropyrido[l,2-a]pyrazines was obtained from an ester group by acidic or alkalic hydrolysis. A side chain carboxyl group was converted into a carboxamide group by the treatment with an amine in the presence of 1-hydroxybenzotriazole (OOJAP(K)OO/ 86659). 

Treatment of the appropriate pipecolic amide 396 with NEta afforded optically active or racemic perhydropyrido[l,2-a]pyrazine-l,4-dione (397) (97USP5703072). (9a5)-Perhydropyrido[l,2-a]pyrazin-3-one (400) was obtained by cyclization of piperidine 398, and the catalytic hydrogenation of quaternary salt 399 over Pd/C (99H(51)2065). 

Cyclization of (25)-2-(rerc-butoxycarbonylaminomethyl)-l-(2-chloro-acetyl)piperidine on the action of NaH in THF gave (9aS)-2-(rerc-butoxycarbonyl)perhydropyrido[l,2-a]pyrazin-4-one (99H(51)2065). 3-Benzyl-2,3,4,4 ,5,6-hexahydro-l//-pyrazino[l,2-a]quinolin-l-ones 413... 

Substituted perhydropyrido[l,2-a]pyrazine-l,4-diones were obtained when methyl A-[2-(benzyloxycarbonylamino)acetyl]-4-substituted pipecoli-nates were hydrogenated over 10% Pd/C catalyst in MeOH, and then the methanolic solutions were refluxed (00JAP(K)00/86659). 

Methoxy-5-nitrophenyl)perhydropyrido[ 1,2-a]pyrazin-3-one was obtained by cyclization of l-(ethoxycarbonylmethyl)-2-[A-(2-methoxy-5-nitrophenyl)aminomethyl]piperidine on the action of NaH in boiling dioxane (99MIP10). 

Perhydropyrido[l, 2-a]pyrazine-1,6-diones and 6a,7,8,9-tetrahydro-5//-pyrido[l,2-a]quinoxaline-6,10-diones were formed when their precursors bond to a resin were cleaved by an acid (01MIP4). 

Cyclocondensation of 2-aminomethylpiperidine 422 and dimethyl oxalate yielded perhydropyrido[l,2-n]pyrazine-3,4-dione 423 (00T1005). 

Racemic /ru -2-(l-naphthylsulfonyl)-7- [4-amino-2-quinaxolinyl)amino-methyl]perhydropyrido[l,2-u]pyrazine was resolved into the optically active enantiomers by means of a Chiralpack column (01MIP20). 

Dichlorophenyl)-2-[2-(perhydropyrido[l,2-u]pyrazin-2-yl)benzyli-dene]thiomorpholin-3-one was claimed as a psychotherapeutic agent (98MIP6). Inhibitory concentration and proportion of high and low affinity... 

Stereostructures of a co-crystal of (li )-l- 4-[(9aA)-perhydropyrido[l,2- ]pyrazin-2-yl]phenyl -2-phenyl-7-hydroxy-l, 2,3,4-tetrahydroisoquinoline with ERa-LBD301-553/C — S triple mutant <2005JME364> and iV-[2-(4-hydroxyphenyl)ethyl]-a-propyl-3-[(4-hydroxyphenyl)methyl]-l,4-dioxo-l,2,3,4,ll,l la-hexahydro-67/-pyrazino[l,2- ]isoquinoline-3-acetamide with fructose-1,6-biphosphatase <2003JBC51176> were determined by X-ray crystallography. The structure of a complex formed from 3-[( -methylphenyl)amino]-4-[(4-methylphenyl)imino]-4//-pyrido[l,2-tf]pyrazine with sodium bis(trimethylsilyl)amide and (norbornadiene)Mo(CO)4 in THF was characterized by single crystal X-ray diffraction <1995JPR38>. 

Amino-2-methoxyphenyl)perhydropyrido[l,2-tf]pyrazine was prepared from a 2-(5-nitro-2-methoxyphenyl)-3-one derivative by catalytic hydrogenation over Pd/C catalyst, followed by the reduction of the 3-oxo group by treatment with BH3-THF complex <1999WO99/042465>. A nitro group was reduced to an amino group in 2-[4-(3-nitrophenyl)piperazin-l-yl]butyl]perhydropyrido[l,2-tf]pyrazine-l,4-dione <2001JME186>, in 8-hydroxy-... 

Naphthylsulfonyl)aminomethyl]perhydropyrido[l,2-4]pyrazine <2001WOO l/85730> and 8-methoxy-2,3,4,4a,5,6-... 

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