An overview of the key routes to the best selling 5-membered ring heterocyclic pharmaceuticals

• Marcus Baumann,
• Ian R. Baxendale,
• Steven V. Ley and
• Nikzad Nikbin

Beilstein J. Org. Chem. 2011, 7, 442–495, doi:10.3762/bjoc.7.57

• indole synthesis a hydrazine, which is most commonly derived from the corresponding diazonium salt, is reacted with a suitable carbonyl compound. Alternatively, the Japp–Klingemann reaction can be used to directly couple the diazonium salt with a β-ketoester to obtain a hydrazone which can then undergo

• the most obvious approach, the direct Fischer indole synthesis, to prepare the core of eletriptan as shown in Scheme 22 is not successful [30]. This is believed to be due to the instability of the phenyl hydrazine species 98 under the relatively harsh reaction conditions required to promote the

• cyclisation. However, this problem could be avoided by using an acid-labile oxalate protected hydrazine 104 as depicted in Scheme 23. The yield of this step can be further improved up to 84% if the corresponding calcium oxalate is used. The Bischler–Möhlau reaction is an alternative indole synthesis employing

Tribenzotriquinacenes bearing three peripheral or bridgehead urea groups stretched into the 3-D space

• Jörg Tellenbröker and
• Dietmar Kuck

Beilstein J. Org. Chem. 2011, 7, 329–337, doi:10.3762/bjoc.7.43

• that, accordingly, the 1:3 mixture of the trinitro compounds 8 and 9 is also reflected by three 13C NMR lines at δ 25.54, 25.46 and 25.40 in the intensity ratio of ca. 3:6:3. Reduction of the mixture of the trinitro compounds 8 and 9 was in the first instance achieved by use of hydrazine with iron(III

• reflux for 15 min and then hydrazine hydrate (97%, 120 mg) added. After heating for 4 h further FeCl3•6H2O (10 mg) and 120 mg N2H4•H2O (120 mg) were added. The mixture was heated under reflux for a total of 24 h, allowed to cool and filtered through silica with ethyl acetate. Removal of the solvent gave

Approaches towards the synthesis of 5-aminopyrazoles

• Ranjana Aggarwal,
• Vinod Kumar,
• Rajiv Kumar and
• Shiv P. Singh

Beilstein J. Org. Chem. 2011, 7, 179–197, doi:10.3762/bjoc.7.25

• hydrazines to yield 5-aminopyrazoles 3 [19][20][21][22][23][24][25][26][27][28]. The reaction apparently involves the nucleophilic attack of the terminal nitrogen of the hydrazine on the carbonyl carbon with the formation of hydrazones 2, which subsequently undergo cyclization by the attack of the other

• -ketonitriles 16 with a substituted hydrazine in the presence of Et3N in ethanol under reflux conditions. The intermediate 16 was obtained from β-ketoester 15 on treatment with TFA, which in turn was synthesized by condensing 4-(phenylsulfonamidomethyl)cyclohexane carboxylic acid or benzoic acid 13

• or 34) on Merrifield resin in the first step. Reaction of the resin-bound sulfonyl intermediate 31 with hydrazine, followed by release from the resin and intramolecular cyclization, afforded 4-arylsulfonyl-3,5-diamino-1H-pyrazoles 32. Reaction of the resin-bound carbonyl intermediate 35 with

A new and facile synthetic approach to substituted 2-thioxoquinazolin-4-ones by the annulation of a pyrimidine derivative

• Nimalini D. Moirangthem and
• Warjeet S. Laitonjam

Beilstein J. Org. Chem. 2010, 6, 1056–1060, doi:10.3762/bjoc.6.120

• of various fused heterocyclic compounds. In recent years, we have reported one-pot cyclizations of DTBA with hydrazine [23][24], hydroxylamine [25], guanidine [26], etc. In addition, one-pot cyclizations of DTBA-derived arylidenes have also been reported. Recently, we reported the synthesis of fused

Recognition properties of receptors consisting of imidazole and indole recognition units towards carbohydrates

• Monika Mazik and
• André Hartmann

Beilstein J. Org. Chem. 2010, 6, No. 9, doi:10.3762/bjoc.6.9

• equiv of 2-amino-4,6-dimethylpyridine, CH3CN/THF, K2CO3, r. t., 3 d (20%); d) potassium phthalimide, dimethyl sulfoxide, 95 °C, 8 h, (57%); e) hydrazine hydrate, ethanol/toluene, reflux, 19.5 h, KOH (43%) [27]; f) 4 equiv of 4(5)-imidazole-carbaldehyde (18), CH3OH, 3 d; g) 4 equiv of 3-indole

An expedient and new synthesis of pyrrolo[1,2-b]pyridazine derivatives

• Rajeshwar Reddy Sagyam,
• Ravinder Buchikonda,
• Jaya Prakash Pitta,
• Himabindu Vurimidi,
• Pratap Reddy Padi and
• Mahesh Reddy Ghanta

Beilstein J. Org. Chem. 2009, 5, No. 66, doi:10.3762/bjoc.5.66

• condensation reactions, such as the condensation of oxazolo[3,2-b]pyridazinium perchlorates with malononitrile, ethyl cyanoacetate and ethyl malonate in the presence of sodium ethoxide [15]; the condensation of 1,4,7-triketones with hydrazine followed by dehydrogenation [16]; the condensation of cyanoacetic

Pd/C-mediated synthesis of α-pyrone fused with a five-membered nitrogen heteroaryl ring: A new route to pyrano[4,3-c]pyrazol-4(1H)-ones

• Dhilli Rao Gorja,
• Venkateswara Rao Batchu,
• Ashok Ettam and
• Manojit Pal

Beilstein J. Org. Chem. 2009, 5, No. 64, doi:10.3762/bjoc.5.64

• category. It involves the reaction of methyl 2-cyano-3,3-dimethylthioacrylate with 1-tetralone and subsequently with hydrazine [8]. Though a number of methods are known for the synthesis of isocoumarins by constructing the pyrone ring [9][10][11][12][13][14][15][16][17] (the second strategy) none has been

Mitomycins syntheses: a recent update

• Jean-Christophe Andrez

Beilstein J. Org. Chem. 2009, 5, No. 33, doi:10.3762/bjoc.5.33

• [4.1.0] ring system. It was necessary to methanolyse the lactone 69 prior to removal of the phthalimide with methyl hydrazine, which occurred with concomitant cyclization to form penultimate intermediate 70. The final ring closure was realized by treatment with camphorsulfonic acid to form lactam 71 in

2-Arylhydrazononitriles as building blocks in heterocyclic synthesis: A novel route to 2-substituted- 1,2,3-triazoles and 1,2,3-triazolo[4,5-b]pyridines

• Saleh M. Al-Mousawi and
• Moustafa Sh. Moustafa

Beilstein J. Org. Chem. 2007, 3, No. 12, doi:10.1186/1860-5397-3-12

• as in 5 and therefore excluding 7 (Scheme 2). Typical of enaminones, compound 9 reacts with naphthoquinone to yield the benzofuran 12 and with hydrazine hydrate to yield pyrazolyl-1,2,3-triazole 13 in good yields. Attempts to convert 4 into oxadiazolylhydrazone 6 by heating in DMF afforded 14 whose

ADDP and PS-PPh₃: an efficient Mitsunobu protocol for the preparation of pyridine ether PPAR agonists

• Paul S. Humphries,
• Quyen-Quyen T. Do and
• David M. Wilhite

Beilstein J. Org. Chem. 2006, 2, No. 21, doi:10.1186/1860-5397-2-21

• hydrazine derivative 7 as the by-product (side reaction in Figure 2),[19] since anion 6 is not efficient in deprotonating the weakly acidic phenol. One way to improve the above redox system is to enhance the basicity of anion 6 by the replacement of the alkoxy group OEt in DEAD with strong electron donating

One-pot synthesis of novel 1H-pyrimido[4,5-c][1,2]diazepines and pyrazolo[3,4-d]pyrimidines

• Dipak Prajapati,
• Partha P. Baruah,
• Baikuntha J. Gogoi and
• Jagir S. Sandhu

Beilstein J. Org. Chem. 2006, 2, No. 5, doi:10.1186/1860-5397-2-5

• through involvement of an azine (obtained from oxidation of hydrazine group). Similarly other α,β-unsaturated carbonyl compounds 2b-e were reacted and the corresponding pyrimido[1,2]diazepines 3b-e were obtained in 78–90% yields and were characterized fully by spectroscopic and elemental analyses. The IR

• % yield. The structure 4 was fully characterized through spectroscopic data and elemental analysis. The IR (KBr) band at 1589 cm-1 reveals the presence of (C=N), which confirmed involvement of hydrazine group in the reaction. The other absorption bands at 1718 and 1676 cm-1 indicated the presence of