Pyrimidine, 2,4-diethoxy

Pyrido(2,3-d pyrimidin 2,4-Diethoxy-carbonyl-5,6,7,8-tetrahydro-E9b/2, 131 [(ROOC)3-1,3,5-triazin + 2rImino—piperidin]... 

Bis(substituted amino)-4,8-bisethylthio (or carboxymethylthio)-pyrimido[5,4-d]pyrimidines (464) are aminated first at the 4-position with primary or secondary amines at 180° (2 hr) and then at the 8-position (200°, 4 hr). The 4,8-bisthioxo derivative of 464 is 4,8-diaminated with ethanolamine (170°, 1 hr). 2,6-Dianilino-4,8-dioxo(or diethoxy or dibenzyloxy) derivatives of 464 react at the 4-and 8-positions with primary or secondary amines at 180°. The 2,4,6,8-tetrachloro derivative is claimed to goto the tetrakis(triethylammonio) compound. ... 

The bromide (2a) reacted smoothly with 2,4-diethoxy-5-methylpyrimi-dine to give, after de-ethylation and deacylation, l-(2-deoxy-/ -D-arabino-hexopyranosyl)thymine (3) (15). The new nucleoside (3) is the first truly competitive inhibitor of a pyrimidine phosphorylase (7), that is, it inhibits the phosphorylase, yet is not a substrate for the enzyme. It was recently shown that 3 enhances the incorporation of 2 -deoxy-5-iodouridine in vivo in cats (8). 

Treatment of pyrimidine-2-thione 184 with A1C13 yielded 6-oxo-6,7-dihydro-4//-pyrimido[6,l-tf]isoquinolin-4-thione 185 (Equation 37) <1998MI337>. Cyclization of 6,7-diethoxy-2-propylaminocarbonyl-l,2,3,4-tetrahydroisoquinoline-l-acetonitrile using NaOMe afforded 9,10-diethoxy-2-imino-3-propyl-l,2,4,6,7,l lb-hexahydropyrimido[6,l-tf]isoquinolin-4-one <1995S863>. Cyclization of l-(2-carboxyethyl)-l,2,3,4-tetrahydroquinazoline-2,4-dione 186 in polyphosphoric acid (PPA) afforded l,2,3,5,6,7-hexahydropyrimido[3,2,T /]quinazoline-l,3,7-trione 187 (Equation 38) <1997CHE96>. 

HO JlXHlCHah II CH3 Xylol/H20/NaOH, Phasen-transfer- Kat. 4- (Diethoxy- thiophosphoryloxy )-2-2-isopropyl-6 tnethyl-pyrimidin 94 200... 

AyCHICH, , h3c-cn/k2co3 5-(Diethoxy-thiophosphoryloxy)-2-iso- propyl-pyrimidin 62 201... 

H0. N 0C2Hs XJn h3c-cn/k2co3 4,6-Bis-[diethoxy-thiophosphoryloxy -2-ethoxy-pyrimidin 78 202... 

Dimethyl-4-hydroxy-pyrimidin und Kaliumcarbonat XII/2, 642 4-(Diethoxy-thiophosphoryloxy)-2-isopropyl-6-methyl- E2, 701... 

Treatment of the intermediate (7), prepared4 from 2,4-diethoxy-pyrimidine and a-acetobromoglucose, with ethanolic ammonia afforded4 cytosine-D-glucoside (8). 

Pyrimidin 5,5-Diethoxy-2,4,6-trioxo-hexahydro- E14a/1, 311 (R2CN2 - R2C(OR)2]... 

H-< 1,2,4-Oxadiazolo[4.3-a]-l,3,5-triazin) 5,7-Dimethyoxy-3,3-dimethyl- E16c, 221 (aus Azido-1.3,5-triazin) Pyrimidin 5-Ethoxycarbonyl-4-hydrazino-2-hydroxy-6-methyl-E16a, 766 (SH - NH-NH2) 2H-l,2,3-Triazol 5-(Diethoxy-methylen-amino)-4-formyl- E4, 565 [C(OR)4 + Amin]... 

Essigsaure (a-Diazoacetamino-acetamino)- -ethylester X/4, 521 Pyridazine 5-Amino-3,6-diethoxy-4-nitro- E9a, 613 (H - N02) Pyrimidin 6-Amino-5-(ethoxycarbo-nyl-methyl-amino)-2,4-dihydroxy- E9b/2,145 (N CH 2 — Ar - NH)... 

Dimethyl-5-ethoxycarbonyl-E16c, 122 (En-azid/Ringschl.) Pyrido[3,4-d pyridazin 1,4-Diethoxy-E9c, 68 (Cl - OR) Pyrido[2,3-d(pyrimidin 1 -Butyl-4-hydroxy-2-oxo-l,2-dihydro- E9c, 97 (2-NH R — 3-COOH—py + Urea)... 

The synthesis of corresponding pyrimidine nucleosides was not possible by the mercuric chloride method. The syntheses succeeded, however, on application of the Hilbert—Johnson procedure. Tetra-O-acetyl-4-thio-D-ribofuranose was transformed with ethereal hydrogen chloride into the glycosyl chloride derivative 254, and this was directly heated for five days with 2,4-diethoxy-5-methylpyrimidine. The anomeric forms of 4-ethoxy-5-methyl-l-(2,3,5-tri-0-acetyl-4-thio-D-ribofuranosyl)-2(lH)-pyrimidinone obtained could be separated... 

Attempts to prepare tetrazolo(l,5-a)pyrimidines in the same manner, from 5-aminotetrazole 329), failed. As a weak acid 329) forms a scarcely soluble sodium salt which in addition shows only poor nucleophilic properties. A conversion could be achieved with 3,3-diethoxy-l-dimethylamino-2-methylpropene 35 b) and 329) (whereas the unsubstituted 35 a) does not give reproducible results) leading to colorless needles of sharp melting point, mp. 116° (82%) which shows by H NMR examination to be in deuteriochloroform an equilibrium mixture of 6-methyltetra-... 

Diethoxy-6-thiocyanato-5-phenylpyrido 2,3-[Pg.102]

It is possible to effect only partial replacement of the bromine of 2,4,6-tri-bromopyrimidine by alkoxyl when a solution of two equivalents of sodium in anhydrous ethanol is used in benzene as solvent and room temperature is not exceeded, then the product is 4-bromo-2,6-diethoxypyrimidine (89% yield).738 If the excess of ethanol is removed from a solution of sodium in ethanol and xylene by distillation and the residue is heated with 4-chloro-6-methoxy-2-pyrimidinamine for 2 hours under reflux, 4-ethoxy-6-methoxy-2-pyrimidin-amine is formed 739 but if more ethanol is present the methoxyl group is also replaced by ethoxyl and the product is 4,6-diethoxy-2-pyrimidinamine. 

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