Efficient and Benign One-Pot Conversion of N-Tosyl-1,4,5,6-tetrahydropyrimidines to Pyrimidines via Tandem β-Elimination and Aromatization

REFERENCES

• (a) Parker , W. B. Enzymology of purine and pyrimidine antimetabolites used in the treatment of cancer. Chem. Rev. 2009, 109, 2880–2893; (b) Jorgensen , W. L. ; Bollini , M. ; Thakur , V. V. ; Domaoal , R. A. ; Spasov , K. A. ; Anderson , K. S. Efficient discovery of potent anti-HIV agents targeting the Tyr181Cys variant of HIV reverse transcriptase. J. Am. Chem. Soc. 2011, 133, 15686–15696; (c) Yaziji , V. ; Rodríguez , D. ; Gutiérrez-de-Terán , H. ; Coelho , A. ; Caamaño , O. ; García-Mera , X. ; Brea , J. ; Loza , M. I. ; Cadavid , M. I. ; Sotelo , E. Pyrimidine derivatives as potent and selective A3 adenosine receptor antagonists. J. Med. Chem. 2011, 54, 457–471; (d) Al-Abdullah , E. S. ; Al-Obaid , A.-R. M. ; Al-Deeb , O. A. ; Habib , E. E. ; El-Emam , A. A. Synthesis of novel 6-phenyl-2,4-disubstituted pyrimidine-5-carbonitriles as potential antimicrobial agents. Eur. J. Med. Chem. 2011, 46, 4642–4647; (e) Semenov , V. E. ; Mikhailov , A. S. ; Voloshina , A. D. ; Kulik , N. V. ; Nikitashina , A. D. ; Zobov , V. V. ; Kharlamov , S. V. ; Latypov , S. K. ; Reznik , V. S. Antimicrobial activity of pyrimidinophanes with thiocytosine and uracil moieties. Eur. J. Med. Chem. 2011, 46, 4715–4724; (f) Mohamed , T. ; Yeung , J. C. K. ; Rao , P. P. N. Development of 2-substituted-N-(naphth-1-ylmethyl) and N-benzhydrylpyrimidin-4-amines as dual cholinesterase and Ab-aggregation inhibitors: Synthesis and biological evaluation. Bioorg. Med. Chem. Lett. 2011, 21, 5881–5887; (g) Gu , S.-X. ; He , Q.-Q. ; Yang , S.-Q. ; Ma , X.-D. ; Chen , F.-E. ; Clercq , E. D. ; Balzarini , J. ; Pannecouque , C. Synthesis and structure–activity relationship of novel diarylpyrimidines with hydromethyl linker (CH(OH)-DAPYs) as HIV-1 NNRTIs. Bioorg. Med. Chem. 2011, 19, 5117–5124; (h) Cha , M. Y. ; Lee , K.-O. ; Kang , S.-J. ; Jung , Y. H. ; Song , J. Y. ; Choi , K. J. ; Byun , J. Y. ; Lee , H.-J. ; Lee , G. S. ; Park , S. B. ; Kim , M. S. Synthesis and biological evaluation of pyrimidine-based dual inhibitors of human epidermal growth factor receptor 1 (HER-1) and HER-2 tyrosine kinases. J. Med. Chem. 2012, 55, 2846–2857; (i) Dowling , J. E. ; Chuaqui , C. ; Pontz , T. W. ; Lyne , P. D. ; Larsen , N. A. ; Block , M. H. ; Chen , H. ; Su , N. ; Wu , A. ; Russell , D. ; Pollard , H. ; Lee , J. W. ; Peng , B. ; Thakur , K. ; Ye , Q. ; Zhang , T. ; Brassil , P. ; Racicot , V. ; Bao , L. ; Denz , C. R. ; Cooke , E. Potent and selective inhibitors of CK2 kinase identified through structure-guided hybridization. ACS Med. Chem. Lett. 2012, 3, 278–283; (j) Moreno , E. ; Plano , D. ; Lamberto , I. ; Font , M. ; Encío , I. ; Palop , J. A. ; Sanmartín , C. Sulfur and selenium derivatives of quinazoline and pyrido[2,3-d]pyrimidine: Synthesis and study of their potential cytotoxic activity in vitro. Eur. J. Med. Chem. 2012, 47, 283–298.
   PubMed Web of Science ®Google Scholar
• (a) Ghanim , M. ; Lebedev , G. ; Kontsedalov , S. ; Ishaaya , I. Flufenerim, a novel insecticide acting on diverse insect pests: Biological mode of action and biochemical aspects . J. Agric. Food Chem. 2011 , 59 , 2839 – 2844 ; (b) Navarro , S. ; Perez , G. ; Navarro , G. ; Mena , L. ; Vela , N. Influence of fungicide residues on the primary fermentation of young lager beer . J. Agric. Food Chem. 2007 , 55 , 1295 – 1300 ; (c) Sarmah , A. K. ; Sabadie , J. Hydrolysis of sulfonylurea herbicides in soils and aqueous solutions: A review . J. Agric. Food Chem. 2002 , 50 , 6253 – 6265 ; (d) Dec , J. ; Haider , K. ; Rangaswamy , V. ; Schaeffer , A. ; Fernandes , E. ; Bollag , J.-M. Formation of soil-bound residues of cyprodinil and their plant uptake . J. Agric. Food Chem. 1997 , 45 , 514 – 520 ; (e) Nezu , Y. ; Miyazaki , M. ; Sugiyama , K. ; Kajiwara , I. Dimethoxypyrimidines as novel herbicides, part 1: Synthesis and herbicidal activity of dimethoxyphenoxyphenoxypyrimidines and analogues . Pestic. Sci. 1996 , 47 , 103 – 113
   PubMed Web of Science ®Google Scholar
• (a) Xu , C. ; Dong , X.-M. ; Wang , Z.-Q. ; Hao , X.-Q. ; Li , Z. ; Duan , L.-M. ; Ji , B.-M. ; Song , M.-P. Triphenylphosphine-cyclometallated iridium(III) pyrimidine complexes: Synthesis, crystal structures, and application in α-alkylation of ketones with alcohols . J. Organomet. Chem. 2012 , 700 , 214 – 218 ; (b) Lippert , B. ; Miguel , P. J. S. Metallatriangles and metallasquares: The diversity behind structurally characterized examples and the crucial role of ligand symmetry . Chem. Soc. Rev. 2011 , 40 , 4475 – 4487 ; (c) Parizel , N. ; Ramírez , J. ; Burg , C. ; Choua , S. ; Bernard , M. ; Gambarelli , S. ; Maurel , V. ; Brelot , L. ; Lehn , J.-M. ; Turek , P. ; Stadler , A.-M. Modulation of self-assembly and magnetism of Cu(II) grids in solution . Chem. Commum. 2011 , 47 , 10951 – 10953 ; (d) Hildebrandt , B. ; Reiß , G. ; Ganter , C. The first structurally characterized N-heterocyclic carbene complex with a ligand derived from pyrimidine . J. Organomet. Chem. 2010 , 695 , 474 – 477 .
   Web of Science ®Google Scholar
• (a) Xue , W. ; Li , L. ; Li , Q. ; Wu , A. Novel furo[2,3-d] pyrimidine derivative as fluorescent chemosensor for HSO4− . Talanta. 2012 , 88 , 734 – 738 ; (b) Lin , L.-Y. ; Tsai , C.-H. ; Wong , K.-T. ; Huang , T.-W. ; Wu , C.-C. ; Chou , S.-H. ; Lin , F. ; Chen , S.-H. ; Tsai , A.-I. Efficient organic DSSC sensitizers bearing an electron-deficient pyrimidine as an effective ∏-spacer . J. Mater. Chem. 2011 , 21 , 5950 – 5958 ; (c) Arrachart , G. ; Carcel , C. ; Moreau , J. J. E. ; Hartmeyer , G. ; Alonso , B. ; Massiot , D. ; Creff , G. ; Bantignies , J.-L. ; Dieudonne , P. ; Man , M. W. C. ; Althoff , G. ; Babonneau , F. ; Bonhomme , C. Organosilicas based on purine–pyrimidine base pair assemblies: A solid state NMR point of view . J. Mater. Chem. 2008 , 18 , 392 – 399 ; (d) Liu , B. ; Zhang , H.-L. ; Liu , J. ; Zhao , Y.-D. ; Luo , Q.-M. ; Huang , Z.-L. Novel pyrimidine-based amphiphilic molecules: Synthesis, spectroscopic properties and applications in two-photon fluorescence microscopic imaging . J. Mater. Chem. 2007 , 17 , 2921 – 2929 ; (e) Wang , C. ; Jung , G.-Y. ; Batsanov , A. S. ; Bryce , M. R. ; Petty , M. C. New electron-transporting materials for light-emitting diodes: 1,3,4-Oxadiazole–pyridine and 1,3,4-oxadiazole–pyrimidine hybrids . J. Mater. Chem. 2002 , 12 , 173 – 180 ; (f) Wang , J.-H. ; Shen , Y.-Q. ; Si , J.-H. Synthesis and solid-state polymerization of 5-(p-methylthio-o-methyl-pyrimidinyl)-2,4-pentadiyn-1-ol and the third-order optical nonlinearity of its derivatives . J. Mater. Sci. 2000 , 35 , 5981 – 5987 .
   PubMed Web of Science ®Google Scholar
• [3 + 3] Two-component cyclization: (a) Burgula , L. N. ; Radhakrishnan , K. ; Kundu , L. M. Synthesis of modified uracil and cytosine nucleobases using a microwave-assisted method. Tetrahedron Lett. 2012, 53, 2639–2642; (b) Mokhtar , M. ; Saleh , T. S. ; Basahel , S. N. Mg–Al hydrotalcites as efficient catalysts for aza-Michael addition reaction: A green protocol. J. Mol. Cata A: Chem. 2012, 353–354, 122–131; (c) Portilla , J. ; Quiroga , J. ; Nogueras , M. ; Cobo , J. Regioselective synthesis of fused pyrazolo[1,5-a]pyrimidines by reaction of 5-amino-1H-pyrazoles and β-dicarbonyl compounds containing five-membered rings. Tetrahedron 2012, 68, 988–994; (d) Nayak , M. ; Rastogi , N. ; Batra , S. Copper-catalyzed cascade reaction of 4-iodopyrazole derivatives with amidines for the synthesis of pyrazolo[4,3-d]pyrimidine derivatives. Eur. J. Org. Chem. 2012, 1360–1366; (e) Lin , M. ; Chen , Q.-Z. ; Zhu , Y. ; Chen , X.-L. ; Cai , J.-J. ; Pan , Y.-M. ; Zhan , Z.-P. Copper(II)-catalyzed synthesis of pyrimidines from propargylic alcohols and amidine: A propargylation–cyclization–oxidation tandem reaction. Synlett 2011, 1179–1183; (f) Hu , M. ; Wu , J. ; Zhang , Y. ; Qiu , F. ; Yu , Y. Synthesis of polysubstituted 5-aminopyrimidines from α-azidovinyl ketones and amidines. Tetrahedron 2011, 67, 2676–2680; (g) Anderson , L. ; Zhou , M. ; Sharma , V. ; McLaughlin , J. M. ; Santiago , D. N. ; Fronczek , F. R. ; Guida , W. C. ; McLaughlin , M. L. Facile iterative synthesis of 2,5-terpyrimidinylenes as nonpeptidic r-helical mimics. J. Org. Chem. 2010, 75, 4288–4291; (h) Bannwarth , P. ; Grée , D. ; Grée , R. Synthesis of new difluoroalkyl propargylic ketones and their use for the preparation of fluorinated heterocycles. Tetrahedron Lett. 2010, 51, 2413–2415; (i) Sleebs , B. E. ; Street , I. P. ; Bu , X. ; Baell , J. B. De novo synthesis of a potent LIMK1 inhibitor. Synthesis 2010, 1091–1096; (j) Bannwarth , P. ; Valleix , A. ; Grée , D. ; Grée , R. Flexible synthesis of pyrimidines with chiral monofluorinated and difluoromethyl side chains. J. Org. Chem. 2009, 74, 4646–4649; (k) Kotljarov , A. ; Irgashev , R. A. ; Iaroshenko , V. O. ; Sevenard , D. V. ; Sosnovskikh , V. Y. 3-(Polyfluoroacyl)chromones and their hetero analogues as valuable substrates for syntheses of 4-(polyfluoroalkyl)pyrimidines. Synthesis 2009, 3233–3242; (l) Bagley , M. C. ; Lin , Z. ; Pope , S. J. A. Barium manganate in microwave-assisted oxidation reactions: Synthesis of solvatochromic 2,4,6-triarylpyrimidines. Tetrahedron Lett. 2009, 50, 6818–6822.
   Web of Science ®Google Scholar
• [4 + 2] Two-component cyclization: (a) Ahmad , O. K. ; Hill , M. D. ; Movassaghi , M. Synthesis of densely substituted pyrimidine derivatives . J. Org. Chem. 2009 , 74 , 8460 – 8463 ; (b) Hill , M. D. ; Movassaghi , M. Observations on the use of microwave irradiation in azaheterocycle synthesis . Tetrahedron Lett. 2008 , 49 , 4286 – 4288 ; (c) Hill , M. D. ; Movassaghi , M. Direct synthesis of substituted pyrimidines and quinazolines . Synthesis 2008 , 823 – 827 ; (d) Robin , A. ; Julienne , K. ; Meslin , J.-C. ; Deniaud , D. Straightforward pyrimidine ring construction: A versatile tool for the synthesis of nucleobase and nucleoside analogues . Eur. J. Org. Chem. 2006 , 634 – 643 .
   PubMed Web of Science ®Google Scholar
• [5 + 1] Two-component cyclization: (a) Sasada , T. ; Aoki , Y. ; Ikeda , R. ; Sakai , N. ; Konakahara , T. Synthesis of tri- or tetrasubstituted pyrimidine derivatives through the [5 + 1] annulation of enamidines with either N,N-dimethylformamide dialkyl acetals or orthoesters and their application in a ring transformation of pyrimidines to pyrido[2,3-d]pyrimidin-5-one derivatives . Chem. Eur. J. 2011 , 17 , 9385 – 9394 ; (b) Fustero , S. ; Piera , J. ; Sanz-Cervera , J. F. ; Román , R. ; Brodsky , B. H. ; Sánchez-Roselló , M. ; Aceña , J. L. ; de Arellano , C. R. New fluorinated 1,3-vinylogous amidines as versatile intermediates: Synthesis of fluorinated pyrimidin-2(1H)-ones . Tetrahedron 2006 , 62 , 1444 – 1451 .
   PubMed Web of Science ®Google Scholar
• (a) Esmaeili , A. A. ; Zangouei , M. ; Fakhari , A. R. ; Habibi , A. An efficient regioselective synthesis of highly functionalized 3-oxo-2,3-dihydro-5H-thiazolo[3,2-a]pyrimidines via an isocyanide-based three-component reaction. Tetrahedron Lett. 2012, 53, 1351–1353; (b) Bera , M. K. ; Reissig , H.-U. A route to alkenyl-substituted 4-hydroxypyridine and pyrimidine derivatives via three-component access to β-alkoxy-β-ketoenamides. Synthesis 2010, 2129–2138; (c) Lechel , T. ; Möhl , S. ; Reissig , H.-U. A concise synthesis of alkoxy-substituted pyrimidine derivatives based upon a three-component access to functionalized enamides. Synlett 2009, 1059–1062; (d) Sasada , T. ; Kobayashi , F. ; Sakai , N. ; Konakahara , T. An unprecedented approach to 4,5-disubstituted pyrimidine derivatives by a ZnCl2-catalyzed three-component coupling reaction. Org. Lett. 2009, 11, 2161–2164; (e) Sheibani , H. ; Seifi , M. ; Bazgir , A. Three-component synthesis of pyrimidine and pyrimidinone derivatives in the presence of high-surface-area MgO, a highly effective heterogeneous base catalyst. Synth. Commun. 2009, 39, 1055–1064; (f) Blangetti , M. ; Deagostino , A. ; Prandi , C. ; Zavattaro , C. ; Venturello , P. N-Metalated imines by reaction of 1,1-diethoxybut-2-ene with aromatic nitriles, as useful intermediates for the synthesis of substituted pyrimidines and cyclopentenones. Chem. Commum. 2008, 1689–1691.
   Web of Science ®Google Scholar
• (a) Klimova , E. I. ; García , J. J. S. ; Klimova , T. ; Apan , T. R. ; López , E. A. V. ; Flores-Alamo , M. ; García , M. M. Synthesis and biological evaluation of novel ethyl 2-amino-6-ferrocenyl-1,6-dihydropyrimidine-5-carboxylates and ethyl 2-amino-6- ferrocenylpyrimidine-5-carboxylates . J. Organomet. Chem. 2012 , 708–709 , 37 – 45 ; (b) Pecchi , S. ; Renhowe , P. A. ; Taylor , C. ; Kaufman , S. ; Merritt , H. ; Wiesmann , M. ; Shoemaker , K. R. ; Knapp , M. S. ; Ornelas , E. ; Hendrickson , T. F. ; Fantl , W. ; Voliva , C. F. Identification and structure–activity relationship of 2-morpholino 6-(3-hydroxyphenyl) pyrimidines, a class of potent and selective PI3 kinase inhibitors . Bioorg. Med. Chem. Lett. 2010 , 20 , 6895 – 6898 ; (c) Araya , I. ; Kanazawa , S. ; Akita , H. Process development and large-scale synthesis of NK1 antagonist . Chem. Pharm. Bull. 2008 , 56 , 176 – 180 ; (d) Hull Jr. , J. W. , Otterson , K. ; Rhubright , D. A new preparation of 5-hydroxypyrimidines derived from carboxylic acids, epichlorohydrin, and ammonia . J. Org. Chem. 1993 , 58 , 520 – 522 ; (e) Cho , H. ; Ohnaka , Y. ; Hayashimatsu , M. ; Ueda , M. ; Shima , K. Synthesis of novel 1,4-, 3,4-, and 4,5-dihydropyrimidines: First successful POCl3 chlorination and regioselective alkoxycarbonylation . Tetrahedron Lett. 1986 , 27 , 6377 – 6380 ; (f) Lorente , A. ; Navio , J. L. G. ; Fuentes , L. ; Soto , J. L. Synthesis of 6-aryl-5-isopropoxycarbonyl-4-thioxo-3,4-dihydropyrimidines from 3-substituted alkyl 2-cyano-3-thiocarboxamidopropenoates . Synthesis 1985 , 86 – 89 ; (g) Weis , A. ; Frolow , F. ; Zamir , D. ; Bernstein , M. Acrolein as a synthon for pyrimidinic compounds: Reaction with benzamidine . Heterocycles 1984 , 22 , 657 – 661 ; (h) Weis , A. L. ; Zamir , D. Acrolein as a synthon for 6-hydroxytetrahydropyrimidines, 1,4(1,6)-dihydropyrimidines, and pyrimidines . J. Org. Chem. 1987 , 52 , 3421 – 3425 ; (i) Solovyev , P. A. ; Shutalev , A. D. Synthesis and oxidative aromatization of 5-acetyl-2-cyanoimino-6-methyl-4-phenyl-1,2,3,4-tetrahydropyrimidine with manganese dioxide . Chem. Heterocycl. Compd. 2009 , 45 , 809 – 814 ; (j) Pews , R. G. Synthesis of 2-alkylpyrimidines via 2-alkyl-1,4,5,6-tetrahydropyrimidines . Heterocycles 1988 , 27 , 1867 – 1871 ; (k) Hitching , G. H. ; Russell , P. B. ; Whittaker , N. Some 2:6-diamino- and 2-amino-6-hydroxy-derivatives of 5-aryl-4:5-dihydropyrimidines: A new synthesis of 4-alky1–5-arylpyrimidines . J. Chem. Soc. 1956 , 1019 – 1028 .
   Web of Science ®Google Scholar
• Mizuhara , T. ; Oishi , S. ; Fujii , N. ; Ohno , H. Efficient synthesis of pyrimido[1,2-c][1,3]benzothiazin-6-imines and related tricyclic heterocycles by SNAr-type C-S, C-N, or C-O bond formation with heterocumulenes . J. Org. Chem. 2010 , 75 , 265 – 268 .
   PubMed Web of Science ®Google Scholar
• (a) Amos , D. T. ; Renslo , A. R. ; Danheiser , R. L. Intramolecular [4 + 2] cycloadditions of iminoacetonitriles: A new class of azadienophiles for hetero-Diels–Alder reactions . J. Am. Chem. Soc. 2003 , 125 , 4970 – 4971 ; (b) Kitahara , K. ; Toma , T. ; Shimokawa , J. ; Fukuyama , T. O-TBS-N-tosylhydroxylamine: A reagent for facile conversion of alcohols to oximes . Org. Lett. 2008 , 10 , 2259 – 2261 ; (c) Ishikawa , T. ; Manabe , I. ; Aikawa , T. Kudo , T. ; Saito , S. Intramolecular catalytic Friedel–Crafts reactions with allenyl cations for the synthesis of quinolines and their analogues . Org. Lett. 2004 , 6 , 2361 – 2364 ; (d) Dong , J. ; Shi , X.-X. ; Yan , J.-J. ; Xing , J. ; Zhang , Q. ; Xiao , S. Efficient and practical one-pot conversions of N-tosyltetrahydroisoquinolines into isoquinolines and of N-tosyltetrahydro-β-carbolines into β-carbolines through tandem β-elimination and aromatization . Eur. J. Org. Chem. 2010 , 6987 – 6992 .
   PubMed Web of Science ®Google Scholar
• Song , B. ; Zheng , X. ; Mo , J. ; Xu , B. Palladium-catalyzed monoselective halogenation of C-H bonds: Efficient access to halogenated arylpyrimidines using calcium halides. Adv. Synth. Catal. 2010, 352, 329–335.
   Web of Science ®Google Scholar
• Molander , G. A. ; Canturk , B. ; Kennedy , L. E. Scope of the Suzuki–Miyaura cross-coupling reactions of potassium heteroaryltrifluoroborates . J. Org. Chem. 2009 , 74 , 973 – 980 .
   PubMed Web of Science ®Google Scholar
• Martinez , A. G. ; Herrera , A. ; Martinez , R. ; Teso , E. ; Garcia , A. ; Osio , J. ; Pargada , L. ; Unanue , R. ; Subramanian , L. R. ; Hanack , M. A new and convenient synthesis of alkyl and aryl pyrimidines . J. Heterocycl. Chem. 1988 , 25 , 1237 – 1241
   Web of Science ®Google Scholar
• Adib , M. ; Mahmoodi , N. ; Mahdavi , M. ; Bijanzadeh , H. R. Microwave-assisted simple, one-pot, four-component synthesis of 2,4,6-triarylpyrimidines under solvent-free conditions . Tetrahedron Lett. 2006 , 47 , 9365 – 9368 .
   Web of Science ®Google Scholar
• Heravi , M. M. ; Sadjadi , S. ; Oskooie , H. A. ; Shoar , R. H. ; Bamoharram , F. F. A direct oxidative route for the synthesis of pyrimidines using heteropolyacids . Tetrahedron Lett. 2009 , 50 , 662 – 666
   Web of Science ®Google Scholar