References and Notes
1a
Schaeffer HJ.
Beauchamp L.
De Miranda P.
Elion GB.
Bauer DJ.
Collins P.
Nature (London)
1978,
272:
583
1b
Elion GB.
Furman PA.
Fyfe JA.
De Miranda P.
Beauchamp L.
Schaeffer H.
Proc. Natl. Acad. Sci. U.S.A.
1977,
74:
5716
2a
Barrio JR.
Bryant JD.
Keyser GE.
J. Med. Chem.
1980,
23:
572
2b
Morris JR.
Peter WH.
Can. J. Chem.
1982,
60:
547
2c
Amblard F.
Nolan SP.
Gillaizeau I.
Agrofoglio LA.
Tetrahedron Lett.
2003,
44:
9177
2d
Chu CK.
Culter SJ.
J. Heterocycl. Chem.
1986,
23:
289
2e
Jeffery AL.
Kim J.-H.
Wiemer DE.
Tetrahedron
2005,
56:
5077
2f
Kumar R.
Nath M.
Tyrrell DLJ.
J. Med. Chem.
2002,
45:
2032
3a
Suwiński J.
Walczak K.
Synthesis
2001,
225
3b
Qu G.-R.
Li Y.
Han S.-H.
J. Chem. Res.
2005,
167
3c
Alahiane A.
Rochdi A.
Taourirte M.
Redwane N.
Sebti S.
Lazrek HB.
Tetrahedron Lett.
2001,
41:
3579
3d
Khalafi-Nezhad A.
Soltani Rad MN.
Khoshnood A.
Synthesis
2004,
583
3e
Singh D.
Wani MJ.
Kumar A.
J. Org. Chem.
1999,
64:
4665
3f
Qu G.-R.
Han S.-H.
Zhang Z.-G.
Geng M.-W.
Xue F.
Can. J. Chem.
2006,
84:
819
4a
Cai Y.
Sun X.-F.
Wang N.
Lin X.-F.
Synthesis
2004,
671
4b
Guillarme S.
Legoupy S.
Aubertin A.-M.
Olicard C.
Bourgougnonc N.
Huet F.
Tetrahedron
2003,
59:
2177
4c
Geen GR.
Kincey PM.
Choudary BM.
Tetrahedron Lett.
1992,
33:
4609
4d
Scheiner P.
Geer A.
Bucknor A.-M.
Imbach J.-L.
Schinazi RF.
J. Med. Chem.
1989,
32:
73
4e
Baker BR.
Tanna PM.
J. Org. Chem.
1965,
30:
2857
4f
Lira EP.
Huffman CW.
J. Org. Chem.
1966,
31:
2188
4g
Khalafi-Nezhad A.
Zarea A.
Soltani Rad MN.
Mokhtari B.
Parhami A.
Synthesis
2005,
419
5a
Loupy A.
Microwaves in Organic Synthesis
Wiley-VCH;
Weinheim:
2002.
p.147
5b
Varma RS.
Green Chem.
1999,
1:
43
5c
Kappe CO.
Angew. Chem. Int. Ed.
2004,
43:
6250
5d
Lidström P.
Tierney J.
Wathey B.
Westman J.
Tetrahedron
2001,
57:
9225
6a
Surendra K.
Krishnaveni NS.
Sridhar R.
Rao KR.
J. Org. Chem.
2006,
71:
5819
6b
Li C.-J.
Chem. Rev.
2005,
105:
3095
6c
Organic Synthesis in Water
Grieco PA.
Blackie Academic and Professional;
London:
1998.
6d
Eissen M.
Metzger JO.
Schmidt E.
Schneidewind U.
Angew. Chem. Int. Ed.
2002,
41:
414
6e
Li C.-J.
Chan T.-H.
Organic Reactions in Aqueous Media
Wiley;
New York:
1997.
6f
Paul S.
Gupta M.
Singh PP.
Gupta R.
Loupy A.
Synth. Commun.
2005,
35:
325
6g
Kormos CM.
Leadbeater NE.
Synlett
2006,
1663
7
Khalafi-Nezhad A.
Zare A.
Parhami A.
Soltani Rad MN.
Nejabat GR.
Can. J. Chem.
2006,
84:
979
8
Dueholm KL.
Egholm M.
Behrens C.
Christensen L.
Hansen HF.
Vulpius T.
Petersen KH.
Berg RH.
Nielsen PE.
Buchardt O.
J. Org. Chem.
1994,
59:
5767
9a
Kikugawa K.
Iizuka K.
Ichino M.
J. Med. Chem.
1973,
16:
358
9b
Lin Q.
Jiang F.
Schultz PG.
Gray NS.
J. Am. Chem. Soc.
2001,
123:
11608
9c
Thompson RD.
Secunda S.
Daly JW.
Olsson RA.
J. Med. Chem.
1991,
34:
2811
9d
Holy A.
Votruba I.
Tloustova E.
Masojidkova M.
Collect. Czech. Chem. Commun.
2001,
66:
1545
10
Qu G.-R.
Geng M.-W.
Han S.-H.
Zhang Z.-G.
Xue F.
Chin. Chem. Lett.
2006,
17:
1149
11
General Procedure for the Michael Addition of Uracil to Acrylonitrile.
To a mixture of uracil (2 mmol, 0.224 g) and Et3N (0.85 mL, 6 mmol) in neat H2O (5 mL), acrylonitrile (6 mmol, 0.4 mL) was added. Then the mixture was put into the cavity of a commercially available single-mode microwave synthesis apparatus equipped with a high sensitivity infrared sensor for temperature control and measurement (MAS-I, Sineo Microwave Chemical Technology Co. Ltd., Shanghai, P. R. of China) and irradiated at 250 W (internal temperature: 100 °C) for 5 min. After completion of the reaction, the mixture was concentrated to dryness under reduced pressure and the residue was purified by column chromatography using EtOAc-cyclohexane (9:1) as the eluent to afford 6a in 82% yield.
12 Compound 6e: yield 74%; yellow crystals; mp 164-165 °C. 1H NMR (400 MHz, DMSO-d
6): δ = 2.940 (t, 2 H, J = 6.4 Hz), 3.982 (t, 2 H, J = 6.4 Hz), 6.318 (d, 1 H, J = 7.2 Hz), 7.606 (d, 1 H, J = 7.2 Hz) 12.766 (s, 1 H) ppm. 13C NMR (100 MHz, DMSO-d
6): δ = 17.07, 44.46, 112.86, 118.65, 141.39, 148.63, 191.05 ppm. IR (KBr): 3188, 3102, 3073, 3042, 2965, 2926, 2252, 1681, 1622, 1451, 1355, 1317, 1255, 1149, 1094, 866, 855, 638 cm-1. HRMS: m/z calcd for C7H7N3OS: 181.0310; found: 181.0320. Anal. Calcd for C7H7N3OS: C, 46.40; H, 3.89; N, 23.19. Found: C, 46.37; H, 3.85; N, 23.11.
Compound 8d: yield 80%; white powder; mp 226-228 °C. 1H NMR (400 MHz, DMSO-d
6): δ = 2.920 (t, 2 H, J = 6.4 Hz), 3.928 (t, 2 H, J = 6.4 Hz), 6.993 (s, 1 H), 7.842 (s, 1 H), 8.147 (s, 1 H) ppm. 13C NMR (100 MHz, DMSO-d
6): δ = 17.14, 45.07, 85.98, 118.82, 147.05, 154.52, 162.81 ppm. IR (KBr): 3364, 3107, 2963, 2945, 2247, 1674, 1650, 1500, 1438, 1410, 1377, 1333, 1280, 1207, 1099, 1028, 988, 824, 778, 653, 628 cm-1. HRMS: m/z calcd for C7H7BrN4O: 241.9803; found: 241.9810. Anal. Calcd for C7H7BrN4O: C, 34.59; H, 2.90; N, 23.05. Found: C, 34.54; H, 2.85; N, 22.97.
Compound 10c: yield 86%; white powder; mp 220 °C (dec.). 1H NMR (400 MHz, DMSO-d
6): δ = 3.145 (t, 2 H, J = 6.4 Hz), 4.354 (t, 2 H, J = 6.4 Hz), 6.980 (s, 2 H), 8.181 (s, 1 H) ppm. 13C NMR (100 MHz, DMSO-d
6): δ = 18.17, 39.26, 118.62, 123.65, 143.23, 150.01, 154.37, 160.20 ppm. IR (KBr): 3494, 3291, 3168, 3155, 3113, 2961, 2947, 2927, 2246, 1631, 1568, 1520, 1481, 1418, 1363, 1326, 1172, 905, 867, 781, 636 cm-1. HRMS: m/z calcd for C8H7ClN6: 222.0421; found: 222.1410. Anal. Calcd for C8H7ClN6: C, 43.16; H, 3.17; N, 37.75. Found: C, 43.14; H, 3.14; N, 37.69.
Compound 10d: yield 77%; pale yellow powder; mp >300 °C. 1H NMR (400 MHz, DMSO-d
6): δ = 3.141 (t, 2 H, J = 6.4 Hz), 4.412 (t, 2 H, J = 6.4 Hz), 7.821 (s, 2 H), 8.211 (s, 1 H) ppm. 13C NMR (100 MHz, DMSO-d
6): δ = 18.58, 39.79, 118.19, 118.65, 141.61, 150.94, 153.53, 157.25 ppm. IR (KBr): 3494, 3418, 3308, 3148, 3087, 3070, 3021, 2979, 2936, 2930, 2860, 2257, 1654, 1597, 1570, 1515, 1479, 1449, 1423, 1409, 1360, 1311, 1257, 644 cm-1. HRMS: m/z calcd for C8H7ClN6: 222.0421; found: 222.0411. Anal. Calcd for C8H7ClN6: C, 43.16; H, 3.17; N, 37.75. Found: C, 43.13; H, 3.11; N, 37.70.
Compound 10g: yield 78%; white powder; mp 144-145 °C. 1H NMR (400 MHz, DMSO-d
6): δ = 3.166 (t, 2 H, J = 6.4 Hz), 3.605 (s, 4 H), 4.455 (t, 2 H, J = 6.4 Hz), 4.712 (s, 1 H), 7.514 (s, 1 H), 8.184 (s, 1 H), 8.230 (s, 1 H) ppm. 13C NMR (100 MHz, DMSO-d
6): δ = 18.18, 42.84, 59.99, 118.24, 119.07, 140.44, 149.18, 152.58, 154.83 ppm. HRMS: m/z calcd for C10H12N6O: 232.1072; found: 232.1081. Anal. Calcd for C10H12N6O: C, 51.72; H, 5.21; N, 36.19. Found: C, 51.70; H, 5.15; N, 36.11.
Compound 10h: yield 73%; white powder; mp 152-154 °C. 1H NMR (400 MHz, DMSO-d
6): δ = 3.134 (t, 2 H, J = 6.4 Hz), 3.498-3.597 (m, 4 H), 4.414 (t, 2 H, J = 6.4 Hz), 4.771 (t, 1 H, J = 5.2 Hz), 8.169 (s, 1 H), 8.208 (s, 1 H) ppm. 13C NMR (100 MHz, DMSO-d
6): δ = 18.39, 42.90, 45.28, 59.46, 60.67, 118.37, 141.14, 149.78, 153.45, 155.38 ppm. HRMS: m/z calcd for C10H11ClN6O: 266.0683; found: 266.0692. Anal. Calcd for C10H11ClN6O: C, 45.04; H, 4.16; N, 31.51. Found: C, 45.02; H, 4.15; N, 31.48.
Compound 10i: yield 76%; white powder; mp 163-164 °C. 1H NMR (400 MHz, DMSO-d
6): δ = 3.087 (t, 2 H, J = 6.4 Hz), 3.572 (s, 4 H), 4.254 (t, 2 H, J = 6.4 Hz), 4.707 (s, 1 H), 5.852 (s, 2 H), 6.958 (s, 1 H), 7.747 (s, 1 H) ppm. 13C NMR (100 MHz, DMSO-d
6): δ = 17.97, 38.47, 42.66, 60.35, 113.39, 118.38, 136.95, 151.28, 155.20, 160.35 ppm. HRMS: m/z calcd for C10H13N7O: 247.1182; found: 247.1174. Anal. Calcd for C10H13N7O: C, 48.58; H, 5.30; N, 39.65. Found: C, 48.51; H, 5.21; N, 39.55.
Compound 12b: yield 83%; pale yellow crystals; mp 72-74 °C. 1H NMR (400 MHz, DMSO-d
6): δ = 1.094 (t, J = 6.8 Hz, 3 H), 3.014 (t, J = 6.8 Hz, 2 H), 4.013 (q, J = 7.2 Hz, 2 H), 4.532 (t, J = 6.8 Hz, 2 H), 8.689 (s, 1 H), 8.783 (s, 1 H) ppm. 13C NMR (100 MHz, DMSO-d
6): δ = 14.04, 33.36, 60.47, 130.98, 147.78, 149.09, 151.58, 152.08, 170.54 ppm. HRMS: m/z calcd for C10H11ClN4O2: 254.0571; found: 254.0562. Anal. Calcd for C10H11ClN4O2: C, 47.16; H, 4.35; N, 22.00. Found: C, 47.08; H, 4.29; N, 21.91.
