Quinazoline reduction

The least troublesome routes to 3,4-dihydro- and 1,2,3,4-tetrahydro-quinazoline are probably the reduction of quinazoline by sodium borohydride, in water for the former or in methanol for the latter. Both must be isolated as salts. The dihydroquinazoline may be formed also by reduction with LAH in ether (65JHC157). In contrast, 5,6,7,8-tetrahy-droquinazoline is best made by primary synthesis from 2-formylcyclohexanone and for-mamide (57CB942) or from cyclohexanone and trisformamidomethane (60CB1402). 

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... 

Reduction of quinazoline with hydriodic acid gives 3,4-dihydro-quinazoline but this can be achieved more satisfactorily by catalytic means. With palladium-charcoal it was found possible to reduce quinazoline to 1,2,3,4-tetrahydroquinazoline. ... 

Catalytic reduction of quinazolines unsubstituted in position 4 using palladium-charcoal, palladium on calcium carbonate, Raney nickel, or Adam s platinum has been used for preparing 3,4-dihydro-... 

Further reduction of 3,4-dihydroquinazoline to l,2,3,Jt-tetTahydro-quinazoline is more difficult, but it can be accomplished with sodium amalgam or by catalytic reduction with palladium-charcoal. 1,2,3,4-Tetrahydroquinazolines have also been prepared by condensing o-aminobenzylamines with various aldehydes and with formaldehyde or methylenediamines (see 3b). 

Reduction of pyrimidine substituted quinazoline 3-oxides, cata-lytically or with phosphorus trichloride, also leads to quinazolines. ... 

Reduction of quinazoline oxides to quinazolines, catalytically (Raney nickel, palladium on charcoal) or with iron and ferrous sulfate in 85% alcohol can be extended to the preparation of benz-substituted quinazolines. ... 

The considerable reduction in the extent of hydration of the quin-azoline cation which results from the insertion of a 4-methyl group has been used in deriving estimates from spectral data of the extent of hydration of other quinazoline species. ... 

Reduction of 2,3,6,7-tetrahydro-177,5i/-pyrido[3,2,l-//]quinazoline-l,3,7-trione and 7-chloro-6-formyl-2,3-dihydro-177,5i/-pyrido[3,2,1 -(/]quinazo-line-l,3-dione with NaBH4 in THF in the presence of 60% aqueous solution of NaOH gave 7-hydroxy and 7-chloro-6-hydroxymethyl derivatives, respectively (01MI28). 

Lee, C.-H. Skibo, E. B. Active site directed reductive alkylation of xanthine oxidase by imidazo[4,5-g]quinazoline-4,9-diones functionalized with a leaving group. Biochemistry 1987, 26, 7355-7362. 

Lemus, R. L. Skibo, E. B. Studies of extended quinone methides. Design of reductive alkylating agents based on the quinazoline ring system, j. Org. Chem. 1988, 53, 6099-6105. 

Nitration of 3,4-dimethoxypropiophenone (91) affords the nitro derivative 92, and catalytic reduction leads to the aminoketone (93). This is then converted to the corresponding formamide by means of formic-acetic anhydride. Treatment with ammonia Completes Construction of the quinazoline ring. 

Reduction of the N(ll)=C(lltf) double bond of l,4-dihydro-2//-pyrazino[2,l-A quinazoline-3,6-diones 30 (R1 = indol-3-ylmethyl R2 = Me) and 31 (R1 = CH2-C6H4-C1- z Rz = Me) was effected with NaBH4. While the m-diastereomer, 30, retained its configuration, the /razw-diastereomer, 31, epimerized during the reaction. <1999JOC7233>. 

Mercaptobenzimidazo[l,2-c]quinazoline reacts with dibromo derivatives under PTC conditions (K2C03/TBAB). Microwave irradiation enabled a striking reduction in reaction times (12 h compared with 15 min) with similar yields (86 and 81%) when compared with conventional heating (Eq. 40) [61]. 

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>. 

A photo-induced electron transfer (from either the sensitizer in its excited state to the oxadiazole in its ground state or from the electron-donor reagent such as triethylamine to the excited oxadiazole) has been suggested as an explanation for the breaking of the O—N bond of 5-aryl-3-methoxy-(or 5-aryl-3-phenyl-)-l,2,4-oxadiazoles (71) upon irradiation. The resulting oxadiazole radical anion underwent either a heterocycliza-tion to give quinazolin-4-ones or reduction to give open-chain products. 

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>. 

Several similar ring-closing strategies have also been published, such as the in situ reduction of the nitro group in 107 followed by condensation of the resulting amino group with the acetyl carbonyl to produce quinazoline 108 in 46% yield <99H2193>. The acetyl transfer product 109 was also produced (32%). 

It is another potent and selective a -adrenoceptor antagonist and quinazoline derivative. It s antihypertensive effect is produced by a reduction in smooth muscle tone of peripheral vascular beds. 

Examples of this ring system (263) were prepared by cyclocondensation of anthranilic acid with the 1,3-thiazole derivatives 262 (82MI1 83AP394). Reductive cyclization of the 4-ethylamino-3-(2-nitrobenzyl)thiazolidines (264) was affected by heating with iron filings and acetic acid to give 4//-3,3a-dihydrothiazolo[4,3- >]quinazoline (265) (87JHC107). 

USP3969506]. Reductive cyclization of 2-methylthio-l-(2-nitrobenzyl]-6-pyrimidines (515) with stannous chloride gave 6,1 l-dihydro-4//-pyrimido[2,l-fc]quinazolin-4-ones (516) (78JHC77). 

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