10- 3,4-dihydro-2/7-pyrimido

Imino-3,4-dihydro-pyrimido[l,2-f][l,3]benzothiazine (PD4404182) was identified as a selective inhibitor of Gram negative Escherichia coli strains <2000JA9334>. 

This ability to form hydroxy derivatives is more characteristic for dihydro-pyrimido[l, 2- ]benzimidazoles 158 and dihydropyrazolo[l, 5-<2]pyrimidines 159. Storing these solutions in chloroform, DMF or alcohols in air leads to the appropriate hydroxy derivatives 176 as a major product along with minor compounds 177 and 178 [158, 171, 172, 173, 174, 175] (Scheme 3.52). Often heterocycles like 176 were the only products of oxidation in air. Surprisingly,... 

A small library of 4,5-dihydro-l,4-benzoxazepin-3(2/f)-ones was prepared by polymer assisted solution phase synthesis based on saheyhe aldehydes, a-bromoaeetie acid esters and primary amines <05MI643>. As noted previously, pyrimido[4,5-fe][l,4]-benzoxazepines (and diazepines, and thiazepines) can be accessed via a neat variation of the Pictet-Spengler cyclisation. The compounds are of interest as inhibitors of particular receptor tyrosine kinases <05JOC9629>. Liu et al. have also reported a synthesis of 5,6-dihydro-pyrimido[4,5-Z)][l,4]benzoxazepines 173, 174 based on a cyclocondensation of the imines 172 <05TL7523>. The advantage of the approach was the incorporation of poorly reactive pyrimidyl amines 170,171. 

Ethoxymethylen-amino)-7-hydroxy-2-thiono-2,3-dihydro- laBt sich durch Hydrolyse und nachfolgende Umsetzung mit salpetriger Saure in 7-Hydroxy-2-mercapio-(j>yrimido[4,5-d]-l,3-thiazol ) uberfiihren319 ... 

When 3-chloropyrimido[4,5-(]pyrida/.in-5-ol (5) is reacted with phosphoryl chloride and N,N-dimethyl- or -diethylaniline (6, R = Me or Et), not only chlorination but also addition of the aniline takes place with formation of 4-[4-(dialkylamino)phenyl]-3,5-dichloro-l,4-dihydro-pyrimido[4,5-c]pyridazine (7).41... 

Amino-heptyf)- 438 2-(2-Amino- 1-hydroxy-athyI)- 496 5-( 4-Amino-2-oxo-1,2-dihydro-pyrimido)-2-aminomethyl-2,5-dihydro- 578 2-(3-Amino-pentyl)- 438... 

A convenient and clean water-mediated synthesis of a series of 4-amino-2-ar-yl-1,2-dihydro pyrimido[l,2-a]benzimidazoles has been reported using alternative nonconventional energy sources [37]. The products were obtained in shorter times with excellent yields (78-89 %) from the multicomponent reaction of 2-ami-nobenzimidazole, malononitrile/ethylcyanoacetate, and carbonyl compounds (Scheme 8.26). The procedure does not involve the use of aity additional reagent/ catalyst, produces no waste, and represents a green synthetic protocol with high atom economy. The combination of microwave irradiation, ultrasonic irradiation, and aqueous-mediated conditions using multicomponent reactions leads to enhanced reaction rates, higher yields of pure products, easier workup, and sometimes selective conversions. Consequently, this protocol should be welcome in these environmentally aware days. 

Pyrimido[4,5- f]pyrimidines may be used as pyrimidine precursors. Thus, the dihydro derivative (736) undergoes alkaline hydrolysis to the amide (737 R = PrCO) which may be deacylated in ethanolic hydrogen chloride to give 5-aminomethyl-2-propylpyrimidin-4-amine (737 R = H) (64CPB393) rather similarly, the pyrimidopyrimidinedione (738) reacts with amines to give, for example, 6-amino-5-benzyliminomethyl-l,3-dimethylpyrimidine-2,4(lFf,3Ff)-dione (739 R = CH2Ph) or the hydrazone (739 R = NH2) (74JCS(Pl)1812). 

Pyrimido[l, 2-a]pyrimidin-2-one, 3,4-dihydro-6,8-dimethyl-hydrobromide synthesis, 3, 361... 

Catalytic debenzylation of 10-(dibenzylamino)-6-(4-rerr-butylphenyl)-3,4-dihydro-2//-pyrimido[2,l-n]isoquinoline 421 (R = PhCH2) over a 5% Pd/C catalyst under hydrogen at atmospheric pressure in acidified EtOH at ambient temperature afforded the 10-amino derivative 421 (R = H) (98JMC1050). 

Ozonolysis of 5,8,9-trihydroxy-2,3-dihydro-l//-pyrimido[l, 2-n]quinoline-3-carboxylic acid (420), obtained from isopyoverdin isolated from Pseudomonas putida BTPl by acidic hydrolysis, gave l-2,4-diaminobutyric acid, which confirmed the hypothesis that heterocyclic chromophores 1 and 4 of pyoverdin and isopyoverdin, respectively, could have the same precursor, and the configuration at C(3) should be 5 (97ZN(C)549). 

Lithiation of 2-(2-alkylphenyl)-l,2,3,4-tetrahydropyrimidines 427 with 1.3 M BuLi in the presence of A/, A/, A, A -tetramethylethylenediamine, then with 1.3 M -BuLi, followed by the addition of a carboxylic acid methyl ester, and treatment of the reaction mixture with pTSA afforded 3,4-dihydro-2/f-pyrimido[2,l-u]isoquinolines 428 after chromatographic work-up (98JMC1050). 

Fluorophenyl)-l ]-hydroxy-2,3,4,1 ]-tetrahydro-6/7-pyrimido[],2-Z)]-isoquinolin-6-one was obtained in the reaction of l-(4-fluorophenyl)-3-oxo-],3-dihydro-2-benzofuran-l-carboxamide and 1,3-diaminopropane in boiling toluene (01BMCL339). 

Trihydroxy-2,3-dihydro-l//-pyrimido[l,2-u]quinoline-3-car-boxylic acid and (420) and its (15)-1-carboxylic acid isomer were isolated from isopyoverdins (97ZN(C)549, 01T1019) and pyoverdins (99MI27), respectively, after acidic hydrolysis in 3 M HCl for 5 days at 110°C. 

ZN(C)153, 00ZN(C)323, 00ZN(C)857, 01MI2, 01MIP4, 01TL5849). 5-Amino-8,9-dihydroxy-2,3-dihydro-l//-pyrimido[l,2-u]quinoline-3-carboxylic acid moiety 4 was also identified as a chromophoric moiety of certain... 

Characteristic H NMR data of (4a/ ,55)- and (4n5,5R)-2-substituted 5- [A-(/e/ /-butoxycarbonyl)-L-tryptophyl]amino perhydropyrido[l,2-c]pyri-midine-l,3-diones were tabulated (01JMC2219). C CPMASS NMR data of 4-(4-methoxyphenyl)perhydropyrido[l,2-c]pyrimidine were reported (00JST73). C NMR data were reported for eight 4-aryl-2,3,5,6,7,8-hexahydro-l//-pyrido[l,2-c]pyrimidin-l,3-diones in the solid state and in CDCI3 solution (00JPO213). The structure of 4-aryl-3,4-dihydro-2//-pyrido [l,2-c]pyrimidine-l,3-diones and their 2,3,5,6,7,8-hexahydro derivatives were characterized by H and C NMR data (99JHC389). Conformational analysis of 6-methyl-2,3,4,6,7,ll/)-hexahydro-l//-pyrimido[6,l-n]isoquino-lin-2-ones 138 and 139 were carried out by H and C NMR studies (97LA1165). 

Reaction of 2-chloro-6,7-dihydro-4//-pyrimido[6,1 -a]isoquinolin-4-ones with liquid NH3 in a pressure bomb at 85 °C for 4h, and with primary and secondary amines in boiling CHCI3 (98MIP15), and anilines in boiling i-PrOFI (00MI17) yielded 2-amino-6,7-dihydro derivatives or their 2,3,6,7-tetrahydro-2-imino tautomers. 

Aryloxy-9,10-dimethoxy-6,7-dihydro-4//-pyrimido[6,1 -a]isoquinolin-4-ones formed in the reaction of 2-chloro derivative and phenols in the presence of K2CO3 in DMF at 90 °C for 2. 5 h or in boiling 2-PrOH for 6-24 h (00MIP20). When 2-isobutylphenol was used the reaction was carried out in the presence of BuLi in THF at —78 °C. 

Cyclocondensation of a-aryl-2-pyridylacetamides and 2-(3,4-dihydroiso-quinolin-l-yl)acetamide with Et2C03 in the presence of NaOEt in boiling EtOH afforded 4-aryl-2,3-dihydro-l//-pyrido[l,2-c]pyrimidine-l,3-diones (99JHC389) and 6,7-dihydro-4//-pyrimido[6,1 -a]isoquinoline-2,4-dione (98MIP15), respectively. 

However, under the same conditions, 6-azidoquinazoline (32) yields the acid-sensitive 5.7-dimethoxy-8,9-dihydro-5//-pyrimido[5,4-c]azcpine (34 16%) by a 1,4-addition of methanol to the initially formed 7-methoxy-9//-pyrimido[5,4-c]azepine (33).153... 

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