A Novel Microwave-assisted One-pot Synthesis of Pyrano[2,3-d]pyrimidines and Pyrido[2,3-d]pyrimidines via a Three Component Reaction in Solvent-Free Condition

Ipsita Devi; Pulak J. Bhuyan

doi:10.1055/s-2003-43367

LETTER

A Novel Microwave-assisted One-pot Synthesis of Pyrano[2,3-d]pyrimidines and Pyrido[2,3-d]pyrimidines via a Three Component Reaction in Solvent-Free Condition

Ipsita Devi, Pulak J. Bhuyan*
Medicinal Chemistry Division, Regional Research Laboratory, Jorhat.785006, Assam, India
Fax: +91(376)2370011; e-Mail: pulak_jyoti@yahoo.com;

Abstract

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Abstract

Three-component cyclocondensation of barbituric acids 1, triethylorthoformate 2 and alkyl nitriles 3 in presence of acetic anhydride proceeds under microwave-assisted conditions to give pyrano[2,3-d]pyrimidines 4 in excellent yields. 6-Aminouracils 5 or 6-hydroxy-aminouracils 7 react with 2 and 3 under identical conditions to yield pyrido[2,3-d]pyrimidines 6 or pyrido[2,3-d]pyrimidine oxides 8 in high yields.

Key words

solvent-free reaction - multicomponent reaction - microwave-assisted reaction - pyrano[2,3-d]pyrimidines - pyrido[2,3-d]pyrimidines

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References

<A NAME="RD23003ST-1">1</A> Tanaka T. Toda F. Chem. Rev. 2000, 100: 1025

<A NAME="RD23003ST-2A">2a</A> Weber L. Illegen K. Almstetter M. Synlett 1999, 366

<A NAME="RD23003ST-2B">2b</A> Armstrong RW. Combs AP. Tempest PA. Brown SD. Keating TA. Acc. Chem. Rev. 1996, 29: 123

<A NAME="RD23003ST-3">3</A> Strecker A. Liebigs. Ann. Chem. 1850, 75: 27

<A NAME="RD23003ST-4">4</A> Robinson R. J. Chem. Soc. 1917, 111: 876

<A NAME="RD23003ST-5">5</A> Hantzsch A. Justus. Liebig. Ann. Chem. 1882, 215: 1

<A NAME="RD23003ST-6A">6a</A> Dossin R. Marcos CF. Marcaccini S. Pepino R. Tetrahedron Lett. 1997, 38: 2519

<A NAME="RD23003ST-6B">6b</A> Kobayashi K. Matoba T. Susuima I. Takabi M. Morikawa O. Konishi H. Chem. Lett. 1998, 551 ; and references cited therein

<A NAME="RD23003ST-7A">7a</A> Yamada T. Omote Y. Yammaka Y. Miyazawa T. Kuwata S. Synthesis 1998, 991

<A NAME="RD23003ST-7B">7b</A> Ross GF. Handtweek E. Ugi I. Tetrahedron 2002, 58: 6127 ; and references cited therein

<A NAME="RD23003ST-8">8</A> Arend M. Westermann B. Risch N. Angew. Chem. Int. Ed. 1998, 37: 1045

<A NAME="RD23003ST-9A">9a</A> Shestopalov AM. Emeliyanova YM. Shestiopolov AA. Rodinovskaya LA. Niazimbetova ZI. Evans DH. Org. Lett. 2002, 423

<A NAME="RD23003ST-9B">9b</A> List B. Castello C. Synlett 2001, 1687

<A NAME="RD23003ST-9C">9c</A> Nair V. Vinod AU. Rajesh C. J. Org. Chem. 2001, 66: 4427

<A NAME="RD23003ST-9D">9d</A> Bagley MC. Cale JW. Bower J. Chem. Commun. 2002, 1682

<A NAME="RD23003ST-9E">9e</A> Cheng JF. Chen M. Arthenius T. Nadzen A. Tetrahedron Lett. 2002, 43: 6293

<A NAME="RD23003ST-9F">9f</A> Huma HZS. Halder R. Kalra SS. Das J. Iqbal J. Tetrahedron Lett. 2002, 43: 6485

<A NAME="RD23003ST-9G">9g</A> Bertozzi F. Gustafsson M. Olsson R. Org. Lett. 2002, 4: 3147

<A NAME="RD23003ST-9H">9h</A> Yuan Y. Li X. Ding K. Org. Lett. 2002, 4: 3309

<A NAME="RD23003ST-9I">9i</A> Bora U. Saikia A. Boruah RC. Org. Lett. 2003, 5: 435

<A NAME="RD23003ST-9J">9j</A> Dallinger D. Gorobets NY. Kappe CO. Org. Lett. 2003, 5: 1205

<A NAME="RD23003ST-10A">10a</A> Pourashraf M. Delair P. Rasmaissen MO. Greene AE. J. Org. Chem. 2000, 65: 6966

<A NAME="RD23003ST-10B">10b</A> Cossy J. Willis C. Bellosta V. Jalmes LS. Synthesis 2002, 951

<A NAME="RD23003ST-11A">11a</A> Gavrilov MY. Novoseleva GN. Vakhrin MI. Konshin ME. Khim.-Farm. Zh. 1996, 30: 39

<A NAME="RD23003ST-11B">11b</A> Ghorab MM. Hassan AY. Phosphorus, Sulfur Silicon Relat. Elem. 1998, 141: 257

<A NAME="RD23003ST-12A">12a</A> Anderson GL. Shim JL. Broom AD. J. Org. Chem. 1976, 41: 1095

<A NAME="RD23003ST-12B">12b</A> Grivaky EM. Lee S. Siyal CW. Duch DS. Nichol CA. J. Med. Chem. 1980, 23: 327

<A NAME="RD23003ST-13A">13a</A> Furuya S, and Ohtaki T. inventors; Eur. Pat. Appl., EP. 608565. ; Chem. Abstr., 1994, 121, 205395

<A NAME="RD23003ST-13B">13b</A> Heber D. Heers C. Ravens U. Pharmazie 1993, 48: 537

<A NAME="RD23003ST-14">14</A> Sakuma Y, Hasegawa M, Kataoka K, Hoshina K, Yamazaki N, Kadota T, and Yamaguchi H. inventors; PCT Int. Appl., WO 9105785. ; Chem. Abstr., 1991, 115, 71646

<A NAME="RD23003ST-15">15</A> Bennett LR. Blankely CJ. Fleming RW. Smith RD. Tessonam DK. J. Med. Chem. 1981, 24: 382

<A NAME="RD23003ST-16">16</A> Davoll J. Clarke J. Eislager EF. J. Med. Chem. 1972, 15: 837

<A NAME="RD23003ST-17A">17a</A> Kretzschmer E. Pharmazie 1980, 35: 253

<A NAME="RD23003ST-17B">17b</A> Shigo S. Hiroshi I. Yakugaku Zasshi 1969, 89: 266

<A NAME="RD23003ST-18">18</A> Ahluwalia VK. Batla R. Khurana A. Kumar R. Indian J. Chem., Sect. B 1990, 29: 1141

<A NAME="RD23003ST-19A">19a</A> Cheng T. Wang Y. Cai M. Youji. Huaxue. 1988, 8: 250

<A NAME="RD23003ST-19B">19b</A> Spada MR. Klein RS. Otter BA. J. Heterocycl. Chem. 1989, 26: 1851

<A NAME="RD23003ST-19C">19c</A> Ahluwalia VK. Kumar R. Khurana K. Bhatla R. Tetrahedron 1990, 46: 3963

<A NAME="RD23003ST-19D">19d</A> Ahluwalia VK. Bhatla R. Khurana A. Kumar R. Indian J. Chem., Sect B 1990, 29: 1141

<A NAME="RD23003ST-19E">19e</A> Ahluwalia VK. Sharma HR. Tyagi R. Tetrahedron 1986, 42: 4045

<A NAME="RD23003ST-19F">19f</A> Ahluwalia VK. Aggarwal R. Alauddin M. Gill G. Khanduri CH. Heterocycle 1990, 31: 129

<A NAME="RD23003ST-19G">19g</A> Broom AD. Shim JL. Anderson CL. J. Org. Chem. 1976, 411: 1095

<A NAME="RD23003ST-19H">19h</A> Wamhoff H. Muhr J. Synthesis 1988, 919

<A NAME="RD23003ST-19I">19i</A> Hirota K. Kuki H. Maki Y. Heterocycles 1994, 37: 563

<A NAME="RD23003ST-19J">19j</A> Srivastava P. Saxena AS. Ram VJ. Synthesis 2000, 541

<A NAME="RD23003ST-20A">20a</A> Bhuyan PJ. Lekhok KC. Sandhu JS. Tetrahedron Lett. 1999, 40: 1793

<A NAME="RD23003ST-20B">20b</A> Bhuyan PJ. Borah HN. Lekhok KC. Sandhu JS. J. Heterocycl. Chem. 2001, 38: 491

<A NAME="RD23003ST-20C">20c</A> Bhuyan PJ. Borah HN. Sandhu JS. Tetrahedron Lett. 2002, 43: 895

In a typical experimental procedure equimolar amounts of 1a (0.312 g, 2 mmol), triethylorthoformate 2 (0.296 g, 2 mmol), malononitrile 3a (0.132 g, 2 mmol) and acetic anhydride (0.648 g, 6 mmol) were added to the reaction vessel of the microwave reactor (Synthewave 402 Monomode Reactor from Prolabo) and allowed to react under microwave irradiation at 360 W and 75 °C for 5 min. The mixture was cooled to r.t. and the solid compound obtained was recrystallised from EtOH (0.392 g, 85%). The compound was confirmed as 4a from the spectroscopic data and elemental analysis. Mp 215 °C. ¹H NMR (300 MHz, CDCl₃): δ = 3.00 (s, 3 H), 3.15 (s, 3 H), 8.10 (s, 1 H), 8.85 (s, 1 H). ¹³C NMR (300 MHz, CDCl₃): δ = 28.3 (3-Me), 36.6 (1-Me), 106.4 (C-4a), 118.8 (CN), 142.6 (C-7), 145.02 (C-6), 147.75 (C-5), 151.2 (C-2), 154.12 (C-8a), 158.0 (C-4). IR: 2217, 1695, 1650 cm^-1. MS: 232 [M⁺]. Anal. Calcd for C₁₀H₈N₄O₃: C, 51.72; H, 3.44; N, 24.13. Found: C, 51.75; H, 3.40; N, 24.15. Similarly compounds 4b-d, were synthesised (Table [1] ) and characterised.

In a simple experimental procedure equimolar amounts of 5a (0.340 g, 2 mmol), triethylorthoformate 2 (0.296 g, 2 mmol), malononitrile 3a (0.132 g, 2 mmol) and acetic anhydride (0.648 g, 6 mmol) were allowed to react under microwave irradiation at 360 W and 75 °C for 2 min in a monomode microwave reactor. The mixture was cooled to r.t. and the solid compound obtained was recrystallised from EtOH (0.438g, 95%). The compound was confirmed as 6a from the spectroscopic data and elemental analysis. Mp 350-352 °C (lit. 352-353 °C). ¹H NMR (300 MHz, CDCl₃): δ = 3.00 (s, 3 H), 3.15 (s, 3 H), 7.75 (br s, 2 H), 8.40 (s, 1 H). IR: 3250, 2213, 1690, 1655 cm^-1 _. MS: 231 [M⁺]. Anal. Calcd for C₁₀H₉N₅O₂: C, 51.94; H, 3.89; N, 30.30. Found: C, 52.00; H, 3.95; N, 30.25. Similarly compounds 6b-d were synthesised (Table [1] ) and characterised.

<A NAME="RD23003ST-23">23</A> Hirota K. Kitade Y. Senda S. J. Heterocycl. Chem. 1985, 22: 345

In a typical experimental procedure equimolar amounts of 7a (0.342 g, 2 mmol), triethylorthoformate 2 (0.296 g, 2 mmol), malononitrile 3a (0.132 g, 2 mmol) and acetic anhydride (0.648 g, 6 mmol) were allowed to react under microwave irradiation at 360 W and 75 °C for 8 min in a monomode microwave reactor. The mixture was cooled to r.t. and the solid compound obtained was recrystallised from EtOH (0.321 g, 65%). The compound was confirmed as 8a from the spectroscopic data and elemental analysis. Mp 218 °C (lit. 218 °C). ¹H NMR (300 MHz, CDCl₃): δ = 3.00 (s, 3 H), 3.15 (s, 3 H), 7.85 (br s, 2 H), 8.15 (s, 1 H). ¹ ³C NMR (300 MHz, CDCl₃): δ = 28.5 (3-Me), 36.8 (1-Me), 107.25 (C-4a), 118.75 (CN), 143.5 (C-7), 145.5 (C-6), 146.55 (C-5), 151.25 (C-2), 154.25 (C-8a), 158.0 (C-4). IR: 3255, 2216, 1715, 1642, 1625 cm^-1. MS: 247 [M⁺]. Anal. Calcd for C₁₀H₉N₅O₃: C, 48.58, H, 3.64, N, 28.34. Found: C, 48.50, H, 3.70, N, 28.40. Similarly compounds 8b-d were synthesised (Table [1] ) and characterised.

<A NAME="RD23003ST-25">25</A> Bhuyan PJ. Borah HN. Boruah RC. Tetrahedron Lett. 2003, 44: 1847