1.2.3.4- Tetrahydro-6/7-pyrido

A sulfoxide was obtained by oxidation of 8-[(4-trifluoromethylmercapto-phenyl)methoxy] derivative 358 with 36% H2O2 in AcOH (98MIP7) and by oxidation of l-[2-(4-thiomorfolin-l-yl)acetyl]-7-(3-methoxyphenyl)-A-methyl-A- [3,5-bis(trifluoromethyl)phenyl]ethyl -5-oxo-1,2,3,5-tetrahydro-pyrido[l,2,3-i/ ]quinoxaline-6-carboxamide with 3-chloroperbenzoic acid (01MIP12). A 7-[(4-fluorophenylsulfonyl)methyl] derivative was obtained by oxidation of a 7-[(4-fluorophenylsulfanyl)methyl]perhydropyrido[l,2-u] prazine with 3-chloroperbenzoic acid in CHCI3 (01EUP1074257). 

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. 

Aus 2,2, 4,4 -Tetranitro-biphenyl-6,6 -dicarbonsaure labt sich bei —1,8 V (in 20% igem Athanol mit Phosphat-Alkali-Puffer) 2,7-Bis-[hydroxyamino -4,9-dihydroxy-5,10-dioxo-4,5,9,10-tetrahydro-(pyrido-[2,3,4,5-1, m,n]-phenanthridin) (F >400°) ge-winnen ... 

Meszaros, Hermecz et al. transformed the quaternary 6,7.8,9-tetrahydro-pyrido[1.2-u]pyrimidinium salts (204) with acid to the carboxylic acids (205 R1 = H)257 and with sodium hydrogen carbonate solution to the l,6,7,8-tetrahydropyrido[l,2- ]pyrimidines (205 R = alkyl).7x2 8 From the alkaline hydrolysis reaction mixture, compounds 206 and 207 were also isolated.133 The quaternary salt (204 R = Me) was transformed with hydrazine hydrate to 6-methylpiperidone and with ammonia to 6-methyl-4-oxo-6.7,8,9-tetrahydro-4//-pyrido[1.2- ]pyrimidine-3-carboxamide and its A-methyl derivative.133... 

When the quaternary salt (272) or the l,6,7,8-tetrahydro-pyrido[l,2- ]-pyrimidine (273) was heated in sodium hydrogen carbonate solution, the pyrido[l,2-a]pyrimidine (274) was formed. This transformation proceeded via addition of water to the C-9a=N-l or the C-9=C-9a double bond, followed by opening of the pyrimidine ring and finally by recyclization through condensation between the carbamoyl group and the oxo function of the piperidine ring.330... 

Baron, A., Sandford, G., Slater, R., et al. (2005) Polyfunctional tetrahydro-pyrido[2,3b]pyrazine scaffolds from 4-phenylsulfonyl-tetrafluoropyridine. J. Org. Chem., 70, 9377-9381. 

Durch intramolekulare Acylierung von 3(5)-(3-Carboxy-propyl)-lH-pyrazol-Derivaten werden 4,5,6,7-Tetrahydro- erhalten z.B.1755 ... 

The Schiff bases, supposedly formed from the reaction of 2-amino-3-aminomethyl-6-methylpyridine and benzaldehyde (also other aromatic aldehydes) in methanolic sodium methoxide,73 may be 1,2,3,4-tetrahydro-pyrido[2,3-d]pyrimidines (see 3).3,72... 

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>. 

Many patents have been issued on the use of pyrogaUol derivatives as pharmaceuticals. PyrogaUol has been used extemaUy in the form of an ointment or a solution in the treatment of skin diseases, eg, psoriasis, ringworm, and lupus erythematosus. GaUamine triethiodide (16) is an important muscle relaxant in surgery it also is used in convulsive-shock therapy. Trimethoprim (2,4-diamino-5-(3,4,5-trimethoxybenzyl)pyrimidine) is an antimicrobial and is a component of Bactrin and Septra. Trimetazidine (l(2,3,4-trimethoxybenzyl)piperazine (Vastarel, Yosimilon) is used as a coronary vasodilator. l,2,3,4-Tetrahydro-6-methoxy-l-(3,4,5-trimethoxyphenyl)-9JT-pyrido[3,4- ]indole hydrochloride is useful as a tranquilizer (52) (see Hypnotics, sedatives, ANTICONVULSANTS, AND ANXIOLYTICS). Substituted indanones made from pyrogaUol trimethyl ether depress the central nervous system (CNS) (53). Tyrosine-and glycine(2,3,4-trihydroxybenzyl)hydrazides are characterized by antidepressant and anti-Parkinson activity (54). 

There are few examples of [5 + 1] cyclizations from pyrimidine intermediates. Two of these involve the chloropropionic ester (194), which gives the 5,6,7,8-tetrahydro-7-one (195) with ammonia (59JCS1849), and the cyclization of a 4-ethynylpyrimidine-5-carboxylate with ammonia to give a pyrido[4,3-. In a recent patent, 5-ethoxycarbonylpyrimidin-4-yl-j8 -alanine derivatives are cyclized with ammonia to pipemidic acid analogues (80GEP2903850). One-carbon pyrimidine [5 +1] syntheses are included in Section 2.15.5.5.1 above. 

Pyrido[2,3-d]pyrimidine-6-carboxylic acid, 5,6,7,8-tetrahydro-5-0x0-synthesis, 3, 221... 

The preparations of over two hundred tetrahydro- and octahydro-pyrido[4,3-d]pyrimidines from piperidines or from purely aliphatic starting materials are described in the patent literature. Fully aromatic examples of the system have been prepared from pyridines and pyrimidines. 

The first recorded pyrido[4,3-d]pyrimidine (133) was synthesized in 1945 by the action of benzamidine on ethyl l-methylpiperid-4-one-3-carboxylate (132). Many more tetrahydro derivatives have been prepared by the similar condensation of various 1,5-substituted... 

Support for this suggestion comes from many quarters. Reduction of the jS-carboline anhydro-bases with sodium and alcohol or with tin and hydrochloric acid gives the 1,2,3,4-tetrahydro derivatives, as does catalytic reduction over platinum oxide in an alkaline medium. On the other hand, catalytic reduction with platinum oxide in acetic acid results in the formation of the 5,6,7,8-tetrahydro-j3-carbolinium derivatives (see Section III,A,2,a). It should be noted, however, that reduction of pyrido[l,2-6]indazole, in which the dipolar structure 211 is the main contributor to the resonance hybrid, could not be effected with hydrogen in the presence of Adams catalyst. 

It is interesting that somewhat similarly 4-oxo-6,7,8,9-tetrahydro-4H-pyrido[l, 2- ]pyrimidine (A) was transformed into 5,6,7,8-tetrahydro-l,8-naphthyridin-4(lH)-one (B) by action of sec-amines (79H1407). Also in this transformation bond-breaking occurs between the ring nitrogen and the carbon of the carboxyl group. 

When 3-phenyl-3//-triazolo[4,5-/]quinoline was heated at 390 00°C, IH-pyrido[2,3-c]carbazole 149 originated. Its structure could be confirmed by unambiguous synthesis from the 8,9,10,1 l-tetrahydro-7//-pyrido[2,3-c]carbazole (52CJC711). 

Polymorphic forms of I and II of 3- 2-[4-(6-fluorobenzo[r/ isoxazol-3-yl)-3,6-dihydro-2//-pyridin-l-yl]ethyl -2-methyl-6,7,8,9-tetrahydro-4//-pyrido [1,2-n]pyrimidin-4-one was characterized by IR spectroscopy (99MIP1). 

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