Quinazoline-2,4-diones, synthesis

Quinazoline-2,4( 1 H,3H)-dione, 7-nitro-synthesis, 3, 110 Quinazolihediones mass spectra, 2, 22 polymers, 1, 298 Quinazoline-2,4( 1 H,3 H)-diones synthesis, 3, 106 O-trimethylsilylation, 3, 91 Quiriazolines addition reactions, 3, 73... 

An experimentally simple synthesis of 2,4(l//,3//)-quinazoline-diones is described1 that uses a thermal cyclization/cleavage as... 

Tripeptides with N-terminal anthranilic acid part were used as starting materials in the solid-phase synthesis carried out on TentaGel resin to prepare 1,4,11,1 l -tetrahydro-2//-pyrazino[2,l-3]quinazoline-3,6-diones with various N-l and N-3 substituents <2003EPP1471066>. Tandem cyclization from [6+0] atom fragments took place in the solid-phase synthesis of 143 from 142. Intermediate 141 was built on bromoacetal resin (Scheme 17) <1998JOC3162>. 

Gordeev MF, Hui HC, Gordon EM, Patel DV, A general and efficient solid phase synthesis of quinazoline-2,4-diones, Tetrahedron Lett., 38 1729-1732, 1997. 

The synthesis of 3,7-dimethylimidazo[4,5- ]quinazoline-6,8(5//,7//)-dione and imidazo[4,5- ]qui-nazoline-6,8(5/7,7/7)-dione, the 1-methyl and 1,9-dimethylated versions (155) of //n-benzoxanthine, respectively, has been achieved using an approach (Equation (75)) based upon an imidazole ring assembly on 7-chloro-3-methyl-6-nitroquinazoline-2,4(l//,3//)-dione, effected by treatment with NH3 or MeNH2 followed by reductive cyclization in HC02H <84JHC79l>. In this same investigation, the 9-(formylamino)-/m-benzoxanthine derivatives (156) were obtained from 7-hydrazino-6-nitro-quinazoline-2,4(l//,3//)-dione precursors. 

Ureidobenzoic acids and derivatives 1 which are readily available from anthranilic acid derivatives and potassium cyanate (cf. p 27) can be cyclized to quinazoline-2,4(l/f,3//)-diones 2 in generally excellent yields. This method makes possible the synthesis of some quinazoline-2,4(1//,3//)-diones on a kilogram scale. The cyclization is usually performed in alkaline medium although cyclizations in acidic mediumhave also been reported. A detailed mechanistic and kinetic study of intramolecular nucleophilic displacement by the ureido func-tional group at the carbonyl carbon of esters and amides of 2-urcidobenzoic acidsand 2-ureidobenzoic acid itself " is available. 

Isatoic anhydrides 11 are transformed with ammonia into quinazoline-2,4(li/,3i/)-diones 12 with concomitant formation of the corresponding anthranilic acids -or anthranil-amides. The reaction lacks generality and has seldom been used for the synthesis of quin-azoline-2.4(177,37f)-diones. 

Reactions of piperazine-2,5-diones with phosphorus pentachloride and phosphorus pentabromide have been described in Sections V.ID and V.IF, respectively. Aromatic aldehydes condense with 3-methylpiperazine-2,5-dione in the presence of acetic anhydride to form mainly mono-A -acetyl derivatives of trans-3-arylidene-6-methylpiperazine-2,5-diones (e.g., 96, R = Ac) (1066). In these products the acetyl group was shown to be attached to position 1 and the 4,5-amide group was found to be sterically hindered. Photolysis formed the cis isomers. Both isomers were deacetylated with methanolic potassium hydroxide (1066). Condensation of 1,4-diacetylpiperazine-2,5-diones with aldehydes has been applied to the synthesis of unsymmetrical 3,6-diarylidenepiperazine-2,5-diones and the reaction has been extended to l,4-diacetyl-3,6-dimethylpiperazine-2,5-diones (1624). Treatment of (96, R = H) with triethyloxonium tetrafluoroborate in dichloromethane gave the monoimino ether, 5-benzylidene-6-ethoxy-3-hydroxy-2-methyl-2,5-dihydropyrazine (97) (1066). l-Methylpiperazine-2,5-dione similarly treated gave 5-ethoxy-l-methyl-2-oxo-l,2,3,6-tetrahydropyrazine (which was condensed with anthranilic acid at 150° to 2-methyl-l,2-dihydropyrazino[2,l-fi]quinazoline-3(4/0.6-dione (98) (1625), and l,4-dimethylpiperazine-2,5-dione gave 5-ethoxy-l,4-dimethyl-2-oxo-1,2,3,4-tetrahydropyrazine and 5,5-diethoxy-l,4-dimethylpiperazin-2-one (1626). 

A recent example of the parallel synthesis of different quinazoline-2,4-dione derivatives (46) demonstrates how to combine the advantages of fluorous synthesis with those of solid-phase chemistry without using expensive perfluorinated solvents [22] (Scheme 3.22). In the beginning, a fluorous benzyl alcohol (47) is adsorbed on fluorous reversed-phase silica gel (FRPSG). Then, in a sequence of splits and reactions, the linker group, which remains bound to the FRPSG by fluorophilic interactions, is converted into a library of differently substituted carboxamido-urethanes (48). These are cyclized and the liberated quinazoline-2,4-diones (46) are eluted from the support with the fluorophobic solvents water and CHjCN/... 

Scheme 3.22 Fluorous synthesis of a library of substituted quinazoline-2,4-diones (46) [22]. The key to this approach is a fluorous benzyloxycarbonyl group on which the target molecules are stepwise constructed and which keeps the different synthetic intermediates bound to fluorous reversed-phase silica gel (FRPSG) during the purification cycles. The structural diversity of the target compound library (46) is introduced by the different anthranilic acid derivatives and primary amines in boxes) (TBTU = 0-(benzotriazol-1-yl)-N,/ /,N, N -tetramethyluronium tetrafluoroborate).

Many ring-fused imidazole derivatives have been synthesized by various methods. Domino Michael addition retro-ene reaction of 2-alkoxyiminoimidazolidines and acetylene carboxylates provided a synthesis of 2,3-dihydroimidazo[l,2-a]pyrimidin-5-(l//)-ones <05T5303>. A single step synthesis of 3,5-dialkyl-9-nitroimidazo[l,2-c]quinazolin-2(3//)-ones from simple carbonyl compounds, primary amines or amino acid methyl esters and 2-azido-5-nitrobenzonitrile has been published <05TL5778>. Diels-Alder reaction of azadienes and benzimidazole-4,7-diones afforded imidazo[4,5-g ]quinoline-4,9-dione derivatives <05EJ01903>. Reaction between isocyanides and dialkyl acetylenedicarboxylates in the presence of 4,5-diphenyl-l,3-dihydro-2//-imidazol-2-one provided a one-pot synthesis of 5//-imidazo[2,l-ft][l,3]oxazine derivatives <05T2645>. Microwave irradiation was employed in the synthesis of 1-ary 1-3-acetyl-1,4,5,6-... 

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