Friedlander condensation

Aryl substituted quinohnes 216 have also been prepared through a microwave-assisted Friedlander condensation between various acetophenones 215 and 2-aminoacetophenones 214 in the presence of a catalytic amount of diphenylphosphate (Scheme 78). These conditions are less acidic than the others reviewed here for the synthesis of quinohnes [138]. 

A direct preparation of selectively protected derivatives of 3-hydroxyquinoline-2-carboxylates 55 was found through use of a modified Friedlander condensation employing the readily accessible O-methyloxime 54 <95JCX3(60)7369>. 

A test library with three novel p38a inhibitory activity has been prepared, among them pyrazolo[3,4-c/]pyrimidine and pyrazolo[3,4-h]pyrazine with potent in vivo activity <06BMCL262>. A convenient route for the synthesis of pyrazolo[3,4-<7]pyrimidine involving Friedlander condensation of 5-aminopyrazole-4-carbaldehyde with formamide or benzamide has been reported <06JHC1169>. A facile synthesis of pyrazolo[3,4-<7]pyrimidines and pyrimido[4,5-<7]pyrimidin-4-one derivatives has been published <06SC2963>. 

One of the earliest syntheses of lavendamycin methyl ester, however, did not employ either the Pictet-Spengler or the Bischler-Napieralski reactions for construction of the /J-carboline ring system. Instead, a palladium-promoted ring closure of aryl pyridine 36 (Fig. 12) was used to prepare /1-carboline 37 by Boger and coworkers [35]. Unfortunately, stoichiometric palladium was found to be necessary, in this case 1.5 equivalents of the tetrakis(triphenylphosphine)palladium(0) being used. Friedlander condensation with aldehyde 38 in the presence of benzyltrimethylammonium hydrox-... 

The Friedlander condensation of 2-aminonicotinaldehyde (221) with ketones and other active methylene compounds gives, as expected, good yields of the 2-substituted or 2,3-disubstituted 1,8-naphthyridines (222) (66JCS(C)315, 67JCS(C)1564, 71JCS(C)2991>. 2-Amino-... 

The Friedlander condensation of 2,6-diaminopyridine-3,5-dicarbaldehyde (393) with various ketones has been reported (77JOC3410). Reaction of the aldehyde with acetophenone, with deoxybenzoin and with a-tetralone generates the 5,10-dihydro-l,9,10-anthyridine derivatives (394 R = H), (394 R = Ph) and (395) respectively, whilst with acenaphthenone the nonacyclic anthyridine (396) is obtained. The condensation between 2-amino-3-ethoxy-carbonyI-l,8-naphthyridine (225) and alkyl carboxylates under basic conditions produces 4-hydroxy-1,9,10-anthyridin-2-ones (397) (79BAP571). 

A palladium-catalyzed amidation of halo(hetero)aromatics substituted in the ortAo-position by a carbonyl function with a primary or secondary amine has been introduced as an alternative to the Friedlander condensation for the synthesis of naphthyridinones (and quinolinones) (Scheme 32) <2004OL2433>. 

The course of the Friedlander condensation between 2-aminobenzaldehyde and the pyrrolidin-3-one (121) depends upon the conditions. In base the pyrrolo[3,2-6]quinoline... 

The camptothecin synthesis of Shen/Dani-shefsky [16] (Scheme 8) starts with the construction of the D ring reaction of 46 with 47 affords 48. The next step (48 49) introduces the C20 ethyl group. Hydroxymethylation of 49 delivers lactone SO. The B ring of the camptothecin precursor 52 should be accomplished by a Friedlander condensation of 10 with 11. For this purpose, a keto group at C2 of the C,D,E ring building block had to be installed. Shen and Danishefsky solved this problem by combination of an aldol condensation (50 —> 51) and a subsequent ozonolysis (51 11). Important for... 

After structural elucidation of lavendamycin (81TL4595), the proposed structure (243) was confirmed by total synthesis of its methyl ester (84H91, 84TL923 85H261). Another total synthesis of its methyl ester was based on the Friedlander condensation for the A-B part, and this part was connected with a )J-carboline moiety (85JOC5790). Moreover, several syntheses of... 

Syntheses of heterocycles by the Friedlander condensation reaction 04MI10. 

Friedlander condensation of aminoaldehyde 203 with cyclic diketones 215 gives heptaannulated heterocyclic systems 216 (1985JOC2407). 

Friedlander condensation of 5-aminopyrazole-4-carboxaldehydes 319 with dimedone furnished pyrazolo[3,4- ]quinolines 320. Subsequent Vilsmeier Hack formylation and sequential cyclocondensation with phenylhydrazine gave Ws-pyrazolo[3,4-b 4,3-/]quinolines (06JHC1169). 

The most commonly used ADA modules contain the pyrimidine-2,4-dione nucleus. Not surprisingly, N-alkylation of thymine or uracil with an alkyl halide provides a simple, one-step method of functionalizing this module. Other ADA units include simple imides (e.g., 10), heterocycle 13, which was used by Kelly in a bisubstrate reaction template [17], and the anthyridinone or anthyridan units in 15 and 18, respectively. The latter modules are synthesized by double Friedlander condensation of 2,6-diaminopyridine-3,5-dicarboxal-... 

The reaction of 148 with 10% HCl-MeOH afforded selective hydrolysis of the amide to form the 3-aminopyridine 149, in which the ring was subsequently closed after treatment with palladium(O) to give the /3-carboline 150. Friedlander condensation of 150 with 2-amino-3-benzyloxy-4-bromo-benzaldehyde (151), which was synthesized in four steps (5S), gave the 2-/3-carbolinequinoline 152. Hydrogen bromide gas debenzoylation of 152 was followed by oxidation with potassium nitrosodisulfonate (Fremy s salt) to obtain Kende s intermediate 131. 

Synthesis of another partial structure of lavendamycin, by Boger et al, was achieved using the same strategy (Scheme 22) (66). In the Friedlander condensation, methyl 3-acetyl-4-aminobenzoate (191) was used in place of the 2-acetylpyridine 183 to obtain 192, which was converted to the 7-... 

A four-step synthesis of 8-amino-7-quinoline carbaldehyde (87) from 8-hydroxyquinoline (88) has been disclosed (Scheme 48) (94T(50) 10685). Major steps involved a Bucherer reaction followed by Claisen type rearrangement, isomerization and ozonolysis. Amino aldehyde (87) underwent Friedlander condensation with 2-acetylpyridine to form 2-pyridyl-l,10-phenanthroline (89). 

A three-step biogenetic-type synthesis of bioactive natural product Luotonin F174 (99H(51)1883) in 38% overall 3deld starts from the natural product pegamine 171 via PCC-oxidation, Friedlander condensation of 172, and chromium trioxide-periodic acid oxidation of 173 (Scheme 34) (02S323). 

The scope of the Friedlander condensation in the preparation of chiral alkyl-substituted 1,10-phenanthrolines was investigated. A range of chiral [x, y-fc]-cycloalkeno-condensed phenanthrolines 343 and 344 were prepared in one step from the chiral pool of steroidal 342 or other cyclic ketones and 302 via base-catalyzed conditions (Scheme 73) (00MI423, 01JOC400). In the case of the major product, aldol bond formation takes place from the sterically less hindered a-carbon (C2) 343 while the steri-cally more hindered a-carbon (C6) 344 reacts to form the minor product (Scheme 73). 

These ligands 347 and 350 were complexed with [Ru] and their properties were studied (05IC8733). The typical yield for the Friedlander condensation steps is about 70%. 

Bell and Liu prepared newly designed heterocyclic receptors via the Friedlander condensation and used them in the complexation of urea. For example, urea complex 376 (88JA3673) is at least 10 times more stable than the best crown ether receptor that also solubilizes solid urea in chloroform (Scheme 83) (90AGE931). 

Queguiner and his group used lithiated pivaloylaminopyridines 407 with aldehydes to synthesize amino ketones. Oxidation of alcohols 408 with CrOs or Mn02 leads to o-aminop)uidyl ketones 409 (Scheme 91). Amides 409 are hydrolyzed to the amines 410 with HCl. Both 409 and 410 were successfully utilized in Friedlander condensations with various ketones that produced naphthyridine derivatives (89JHC105). 

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