4- Amino-7- -5//-pyrrolo

The use of pyrimidines as precursors for pyrrolo[3,4-rf]pyrimidines is the most common synthetic approach. 6-Phenyl-7-(substituted)amino-pyrrolo[3,4-ii]pyrimidine-2,4(l//,3//)-diones (164) are readily obtained from the reaction of 5-formylpyrimidines (163) with arylamines (Equation (54)) <89BCJ3043>. Formation of the Schiff base, followed by cyclization, is the proposed pathway. A more traditional approach is found in the conversion of the cyanoester (165), via the amide, to the corresponding pyrrolopyrimidine (166) (Equation (55)) (88LA643). 

AH-Pyrrolo[3,4-c]isoxazole, 3-amino-biological activity, 6, 1024 4H-Pyrrolo[3,4- c]isoxazole-5(6/7)-carboxylic acid, 3-amino-ethyl ester... 

Pyrrolo[3,2-6]pyridine, 2-methyl-synthesis, 4, 527 Pyrrolo[3,2-c]pyridine, 4-amino-nucleophilic reactions, 4, 507 Pyrrolo[3,2-c]pyridine, 2,3-dihydro-reactions, 4, 512... 

In addition, Namazi and coworkers expanded the DHPM core by constructing pyrrolo[3,4-rf pyrimidines via the classical approach. First, DHPM 59 was delivered in 60% yield using the standard Biginelli conditions. 59 was then brominated in high yield to afford 60. Substitution of bromide 60 with methylamine followed by cyclization of the intermediate amino ester furnished pyrrolo[3,4-rf pyrimidine 61 in 53% yield. 

This method has been applied to a large-scale preparation of 6-bromoindole, which reacts with various arylboronic acids via the Suzuki reaction to afford 6-aryhndoles fEq. 10.50. 6-Bromo-5-methoxyindole for use in the synthesis of marine bromoindole " and 5-amino-7-ethoxycarbonyhndole for use in synthesis of l//-pyrrolo[3,2-g quina2ohne ring system fEq. 10.51 " have been prepared from the appropriate o-nitrotoluene. 

Besides high effectiveness in the diastereoselective control of nucleophilic addition reactions, another major goal in the design of chiral auxiliaries is the use of readily available, chiral starting materials. The hexahydro-l//-pyrrolo[l,2-c]imidazole derivatives 9a-e are examples which use the inexpensive amino acid L-proline (7) as starting material. 

Besides furo[2,3-d]pyrimidines, 6-substituted 5H-pyrrolo[2,3-h]pyrazines have also been obtained in a microwave-promoted one-pot process starting from N-mesyl protected 2-amino-3-chloropyrazine (Scheme 60) [74]. The... 

A development of the reaction described above for the synthesis of pyrrolo[2,l- [l,2,4]triazines using l-aminopyrrole-2-carbonitrile and N,N-dimethyldichloromethyl-iminium chloride utilising ethyl 4-amino-3-cyanopyrazolo[5,1 -c] [ 1,2,4]triazine-8-caiboxylate 60 yields pyrazolo[5,l-c]pyrinudo[4,5-e][l,2,4]triazines 61 <96T3037>. 

Reduction of the nitro group in 70 with zinc in hot sodium hydroxide results in formation of pyrrolo[2,l-(f][l,2,5]benzotriazepine 71 by intramolecular coupling of the amino group with the newly formed nitroso group (Scheme 16). If the reduction is carried out under the less rigorous conditions of zinc in aqueous ammonium chloride the intermediate hydroxy compound is formed <96T10751>. 

Perfluoroalkyl)-5 -deoxy-5 -fluoro- and 5-(perfluoroalkyl)-2, 5 -di-deoxy-5 -fluoro-uridines were prepared " from 840 and 834, respectively, using perfluoroalkyl-copper complexes. Among them, 5 -deoxy-5 -fluoro-(846) and 2, 5 -dideoxy-5 -fluoro-5-(perfluoroethyl)uridine (839) were particularly effective against Ehrlich ascites carcinoma. 5-Hydroxyl (847) and 5-amino or 5-alkylamino (5-NHMe, -NHBu, -NHCH2Ph, -morpholino, -piperidino, and -pyrrolo) analogs (848) of 840 were prepared. The a anomer of 5 -deoxy-5 -fluorouridine (840) was also synthesized. "... 

Furthermore, oxazoles of type 9-82 bearing a secondary amino functionality can be converted into pyrrolo[3,4-b]pyridines 9-86 by reaction with appropriate acid chlorides 9-83 in a triple domino process consisting of amide formation/hetero Diels-Alder reaction and retro-Michael cycloreversion via 9-84 and 9-85 (Scheme 9.17). The pyrrolo[3,4-fc]pyridines can be obtained in even higher yields when the whole sequence is carried out as a four-component synthesis in toluene. Here, 1.5 equiv. NH4C1 must be added for the formation of the now intermediate oxazoles [56b]. 

It should be also noted that, in a very recent publication, Liu and coworkers were successful in applying microwave radiation within their domino approach towards the synthesis of pyrrolo[2,l-fc]quinazoline alkaloids such as deoxyvasicinone, 8-hy-droxydeoxyvasicinone, mackinazolinone and isaindigotone, which exhibit a promising broad spectrum of biological activities. In the case of isaindigotone, the authors were able to extend their strategy to a three-component procedure, which comprises the domino conversion of anthranilic acids and Boc-protected amino acids into the tricyclic core skeleton [43]. 

Representatives of the pyrrolo[3,2-/][l,7]naphthyridine ring system, viz. 61, have been obtained by palladium-catalyzed cyclization of the corresponding 5-alkenyl-6-amino[l,7]naphthyridines (Scheme 19) <2002H(56)443>, although this reaction appears not to be general and its scope is as yet undefined. 

A one-pot synthesis of 3-methyl-5-aryl-4//-pyrrolo[2,3-<7]isoxazoles was performed in high yields by Sharpless epoxidation of 4-amino-3-methyl-5-styrylisoxazoles <06TL4957>. 1,2,4,5-Tetrazines were condensed with isoxazolylcyclobutanones in methanolic KOH to give conformationally restricted 6-isoxazol-5-yl-6,7-dihydro-5//-[l,2]diazocin-4-ones <06JOC2480>. 

The pyrrolo[3, 4 2,3]azepino[4,5,6-cd] indole-8,10-dione system can be accessed by reaction, under conditions used for the Pictet-Spengler reaction, of the imines from condensation of 3-amino-4-(3-indolyl) pyrrolin-2,5-diones with aldehydes or ketones. Cyclisation to the pyrrolo-P-carbolines did not occur under the conditions <00JHC1177>. 

A second patent application appeared in 2005, in which a series of pyrrolo[l,2-b]pyridazine-5,6-dicarboxylates was disclosed [31]. Several of the described compounds (exemplified by structure 8) were reported to have IC50 values of < 0.5 iM against DGAT-1. Various hydrophobic and amino substitutions at positions 4 and 7, and 2, respectively, were tolerated on the heterocyclic ring, along with heterocyclic replacements for the 6-substituted ethyl carboxylate. 

The amino pyrrole 29 derived from the reaction with phenylhydrazine <1998JOC9131> was found to undergo an acid-catalyzed intramolecular condensation with the carbonyl present to give the 3//-pyrrolo[l,2-A pyrazole 30 ring system in a good yield (75%) (Equation 2). 

A parallel library of optically active bicyclic tertiary amines 127 bearing N-chiral bridgehead nitrogen atoms was readily prepared by condensation of primary amines, cyclic amino acids 126, and aldehydes. This method gives access to a large variety of substituted hexahydro-l/7-pyrrolo[l,2-/ ]imidazol-l-ones of type 127 (Scheme 16). These... 

The rhodium acetate complex catalyzed the intramolecular C-H insertion of (/ )-diazo-fR)-(phenylsulfonyl)acet-amides 359 derived from (f )-amino acids to afford in high yield the 6-benzenesulfonyl-3,3-dimethyl-7-phenyl-tetrahydro-pyrrolo[l,2-c]oxazol-5-one 360 (Equation 63) <2002JOC6582, 2005TL143>. 

Reaction of the thia-amino acid 392 with trifluoroacetic anhydride gave the 2,2,2-trifluoro-l-[7-(trifluoromethyl)-l//-pyrrolo[l,2-c]-[l,3]thiazol-6-yl] ethanone pyrrole 395. The formation of the pyrrole can be rationalized by a sequence involving trifluoroacetylation of the enamine 392 affording dione 393 followed by loss of water and carbon dioxide to give the aromatic product 395. These decarboxylations afford fluorinated derivatives of heterocyclic skeletons known to exhibit interesting biological activity (Scheme 58) <2000T7267>. 

In the search of new methodologies for the asymmetric synthesis of nonproteinogenic amino acids, 8-methyl-4,8a-diphenyltetrahydro-17/-pyrrolo[2.1 -r l, 4 oxazinc-l, 6(7//)-dionc 62, obtained as described in Scheme 24 (Section 11.11.7.3), was selectively reduced at the lactam carbonyl with BH3 and further opened by hydrogenolysis to give syn-disubstituted proline derivative 64 in 95% yield <1997SL935> (Scheme 6). It is noteworthy that hydrogenolysis did not affect the benzylic position of bicyclic compound 63. 

A series of l/f-pyrrolo[2,l-r][l,4]oxazin-l-ones 196 are also the product of an LJgi multicomponent reaction between proline (and also other a-amino acids that gave the corresponding monocyclic compounds) and several isonitriles in the presence of commercially available glycolaldehyde dimer (Equation 3) <20010L4149>. 

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