Quinazolinone, reduction

Quinazolin-4(3H)-one, 3-phenyl-reduction, 3, 75 Quinazolinones polymers, 1, 298 reactions, 3, 89 structure, 3, 66-67 synthesis, 2, 96 3, 133 thiation, 3, 89 Quinazolin-4-oties 2,3-disubstituted Grimmel synthesis, 3, 109 mass spectra, 2, 22... 

The ethers (40) are hydrolyzed in high yields, by boiling water (4 hr), to 4-hydroxyquinazoline 1-oxide, and their structures were deduced by methylation followed by reduction to 3-methyl-4(3H)-quinazolinone (Scheme 6). These N-1 oxides show the typical reac-... 

Reduction of 3-methyl-4(3H)quinazolinone with lithium aluminum hydride is known to give 3-methyl-l,2,3,4-tetrahydroquinazoline. The most interesting tetrahydroquinazoline is Trbger s base ° since it has added to our knowledge of the stereochemistry of tri-... 

Quinazolines undergo many of the same reactions as pyrimidines, such as the modification of an amino group. Gangjee and co-workers reported the reductive alkylation of diaminoquinazolinones 141 with various aryl carbonyl compounds 142, which regioselectively produced quinazolinones 143 <00JHC1097>. 

As Scheme 97 shows, employing macrocyclic lactams 263 and o-azidoben-zoyl chloride, 4(3//)-quinazolinones (264) are obtained with the aid of an aza-Wittig strategy. Reductive cleavage of the C-2 —N-3 bond of quinazo-... 

The reduction of quinazolinone 242 with hydrogen at 3 atm in the presence of a palladium-on-calcium-carbonate catalyst furnished perhydroquin-azolinone 243. The stereochemistry of 243, with four chiral centers, was not investigated (70M1767). 

Armarego studied the reduction of quinazolinones 244 and cyclopenta-pyrimidinones 246. The reduction with platinum(IV) oxide as catalyst was found to be highly stereospecific, resulting only in the cw-fused derivatives 245 and 247, respectively [74JCS(P1)2313 76JCS(P1)1415]. 

Reductive alkylation of carboxamides 262 with sodium borohydride in the presence of an oxo compound furnished the carboxamides 265. In this process for the cis or trans isomers of 262 with acetone or cyclohexanone, the quinazolinone intermediates 266 [R = R = Me R, R = (CH2)s] of the reductive alkylation were also isolated and characterized [87-ACSA(B)228 91AX(C)2632]. 

The hydrogenation of 3-substituted 4(377)-quinazolinones 402 has been performed with both palladium and platinum oxide to give the 1,2-dihydro derivatives 403 <2001JME1971, 2004H(63)2019>, while the reduction of 2(1//)-quinazolinones 404 is readily performed with sodium borohydride in methanol <1990H (30)493 >. 

The chiral, reactive 2(3// )-quinazolinone 406 underwent diastereoselective reduction with lithium tri(fer7-butoxy)-aluminium hydride at —60°C to generate the 1,4-dihydro derivative 407 <2003JOC754>, while nickel boride reduction of the 2-thioxoquinazoline 408 gave the 2,3-dihydro-4(177)-quinazolinone 409 <2003JHG677>. 

Reduction of the benzene ring of quinazolines can also occur, as demonstrated by the platinum oxide hydrogenation of the chiral 4(3//)-quinazolinone 410, which gave a mixture of the three diasteromeric octahydro-4( 1//)-quinazolinones 411-413 <2004TA3545>. 

The reduction of the 1,2-double bond in a series of 7-chloro-6-sulfamyl-4(3//)-quinazolinones (110) by sodium borohydride in the presence of aluminum trichloride has been reported.138 Lithium aluminum hydride caused the conversion of 3-methyl-4(3/7)quin-azolone to 3-methyl-l,2,3,4-tetrahydroquinazoline.185a... 

The reductive ring cleavage that prevails with 4-quinazolinone and LAH has been the subject of several reports. Interest was first shown after the... 

Reduction of the quaternary salt 327 with sodium borohydride yielded the 4-phenylhexahydropyrrolo[2,l-i>]quinazolinone 339. A diastereomeric mixture of perhydro derivatives was obtained when the methosulfate 340 was reduced with sodium borohydride. - ... 

Bemath, Fiilop and co-workers " - " studied the reduction of compounds of types 224 and 225. On reduction with sodium borohydride in methanol or by hydrogenation over platinum oxide in ethanol or acetic acid, the m 5-decahydropyrido[2, l- )]quinazolinone 341 and its quaternary derivative 342 gave exclusively the perhydro derivative 343. - °... 

Reduction of the azepino[2, l- )]quinazolinone 348 with sodium borohy-dride in methanol led to the ring-opened product 349 at ambient temperature and to the azepino[2,l- >]quinazolinone 350 at — 20°C. ... 

At the dropping mercury electrode the reduction of the cyclic azomethine bond of C = N heterocycles is well known3. Under the conditions of controlled potential electrolysis at a large-scale mercury pool electrode two partially saturated pyrido[2,l-b]quinazolinones 3 were reduced with excellent diastereoselectivity4. 

Reduction. RujfCOlia catalyzes the reduction of nitroarenes with CO. 4(3//)-Quinazolinones are obtained from A(-(2-nitrobenzoyl)amides. In the presence of montmorillonite-bipy Pd(II) the reaction leads to methyl carbamates. ... 

Reduction of the pyrimidone ring in quinazolinone systems can be easily achieved. For example, hydrogenation of 110 under conventional conditions gave the hydroquinazolinone 111 as reported by Drizin and co-workers <01JMC1971>. 

A facile route to benzoaimelated macrocyclic 1,4-diamines has been developed via quinazolinone aimelation of lactams, followed by reductive ring... 

Since Watanabe s synthesis of 4(3H)-quinazolinones in 1993 via transition-metal catalyzed reductive N-heterocychzation [ 181 ], several catalytic methods for quinazoline synthesis have been developed [182-186]. For example, palladium-catalyzed cyclocarbonylations of halides with appropriate reactants provided regioselective synthesis of 4(3H)-quinazolinone derivatives [182] and indoloquinazolines [184]. Also selenium-catalyzed reductive N-heterocyclization to quinazolinones has been developed by Sonoda et al. [183]. Copper-catalyzed heteroannulation with alkynes has been developed as highly region- and stereoselective route to 2-(2-arylvinyl)-l,2,3,4-tetrahydroquinazolin-4-ones 64 by Kimdu et al. [ 185] (Scheme 12). Recently, condensation of anthranylamide with various aldehydes to 4-quinazotinones has been found to give excellent yields in the presence of cupric chloride [186]. 

The simple synthesis of antimycotic alkaloid tryptanthrin 17 via the quinazolinone annelation is summarized also in Scheme 18. Quinazolinone annelation of commercially available isatin 84 under the shown conditions gave 17 in 43% overall yield (Scheme 18) [222]. As the second route, oxindole 82 was annelated to indolo[2,l-fo]quinazolin-12(6ff)-one 83, which could be converted to 17 by air-oxidation but only in the modest yield [222]. Recently an efficient procedure for synthesis 17,16 and luotonin A (26), etc. has been reported using cyclocondensation of iminochloride and methylanthranylate, followed by further manipulations by Jahng et al. [229]. Several known attractive routes to 17 involves cyclocondensation of isatin with isatoic anhydride by Mitscher et al. [230], (Ru)3(CO)i2-catalyzed reductive J -heterocycUzation by Watanabe et al. [182,223]. 

Several ruthenium and platinum complexes catalyse the reductive N-heterocyclisation of N-(2-nitrobenzoyl)amides (51) under carbon monoxide pressure to afford the corresponding 4(3H)-quinazolinone derivatives (52) in good yields (eq. 26, Tables 16 and 17) [90] ... 

The Discovery synthesis shown in Scheme 3 was linear by design and, therefore, less efficient for larger scale manufacture. As is always the case, however, the Process Research and Development group benefitted greatly from this previous work. The synthesis of the quinazolinone core 2 will be described in more detail later. The major issues widi the Discovery route from a scale-up perspective were the preparation and isolation of the dialdehyde 3 and the subsequent aldol addition/elimination to form 1, which had the potential for "dimer" formation by the reaction of 1 with a second molecule of 2. Finally, a reductive amination of 1 with diethyl amine provided CP-392,110 (racemic CP-465,022), albeit with variable yields. 

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