Pyrido quinazoline carbonylation

Bond orders, charges on the atoms in 1 l//-pyrido[2,l-Z)]quinazolin-l 1-one and its protonated form were calculated by quantum chemical calculations by the semiempirical AMI method. According to the results, the equilibrium conformation of the ring in 1 l//-pyrido[2,l-Z)]quinazolin-l 1-one is planar, while l//-pyrimido[l,2-u]quinolin-1-one adopts a conformation close to a half-chair due to the unfavorable interactions between the oxygen atom of the carbonyl group and the ring C-10 atom in the pen-position (97MI22). 

A unique Pd-catalyzed carbonyl insertion reaction of 197 furnished pyrido[2,l-b]quinazoline 198, an antiallergy agent [158]. This particular outcome may be substrate-specific. 

The 9-methyl group on 6,7,8,9-tetrahydro- and 1,2,3,4,6,7,8,9-octahydro-117/-pyrido[2,l-6]quinazolin-l 1-ones occupies a quasi-axial position due to the 1-3 allyl-type strain, which would develop between the 9-methyl group and the neighboring C(11)=0 carbonyl group if the methyl group were in a quasi-equatorial position (87JHC1045). 

Bromo-ll//-pyrido[2,l-b]quinazolin-ll-one and its 8-methyl and 8-isopropyl derivatives (127, R = Br, R1 = H, Me, iPr) were treated with carbon monoxide and nickel carbonyl in wet dimethylformamide in the presence of calcium hydroxyde to yield 2-carboxylic acid derivatives (127, R = COOH, R1 = H, Me, iPr). 2-Bromo-8-isopropyl-ll//-pyrido[2,l-b]-quinazolin-ll-one (127, R = Br, R1 = iPr) was reacted with copper(I) cyanide in iV-methyl-2-pyrrolidone at 180°C for 10 h, then with ferric chloride hexahydrate in diluted hydrochloric acid at 90°C for 30 min to give the 2-cyano derivative (127, R = CN, R1 = iPr) (85CP1189509). 

Carbonyl insertion into 5-substituted 2-(o-bromo-/>-isopropylphenyl-amino)pyridines (275) in the presence of bis(triphenylphosphine)palla-dium(II) chloride, triphenylphosphine, and tributylamine under 200 psi-pressure of carbon monoxide at 100°C in aqueous ferr-butanol or dimethyl-formamide gave 8-substituted 2-isopropyl-l 17/-pyrido[2,l-b]quinazolin-l 1 -ones (276) (87JOC2469). 

V-Substituted-1,2,3,4-tetrahydroisoquinolin-l-ones (26) can be prepared in good yield by carbonyla-tion of A/-alkyl-o-bromophenefliylamines in the presence of catalytic amounts of Pd(OAc)2/PPh3. Similarly substituted 2-(2-bromoanilino)pyridines undergo carbonyl insertion to produce pyrido[2,l-b]quinazoline derivatives in good yield (equation S7). ... 

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