Synlett 2010(7): 1107-1109  
DOI: 10.1055/s-0029-1219544
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Efficient One-Pot Synthesis of 6-Arylpyrrolo[3,2-d]pyrimidines from 6-Arylethynyl-5-nitropyrimidines

Inga Cikotiene*, Erika Pudziuvelyte, Algirdas Brukstus
Department of Organic Chemistry, Faculty of Chemistry, Vilnius University, Naugarduko 24, 03225 Vilnius, Lithuania
Fax: +370(5)2330987; e-Mail: inga.cikotiene@chf.vu.lt;
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Publikationsverlauf

Received 14 January 2010
Publikationsdatum:
23. Februar 2010 (online)

Abstract

A highly concise one-pot synthesis of 6-arylpyrrolo[3,2-d]pyrimidines via conjugative addition reaction of secondary amines to 6-arylethynyl-5-nitropyrimidines and subsequent reduction is described.

    References and Notes

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11

Typical Procedure for the Preparation of 2,4-Disubstituted 6-Arylpyrrolo[3,2- d ]pyrimidines 4a-o To a solution of the corresponding 6-arylethynyl-5-nitro­-pyrimidine 1a-p (0.3 mmol) in MeOH (5 mL) freshly distilled Et2NH (21,9 mg, 0.3 mmol) was added. The resulting reaction mixture was refluxed for 15 min, then deeply red solution was cooled to r.t., 10% Pd/C (0.33 mg, 0.03 mmol) was added, and the resulted mixture was stirred under H2 atmosphere for 2 h. After the completion of the reaction, the catalyst was filtered off, the mother liquid was evaporated under reduced pressure, the residue washed with H2O, filtered, and recrystallized to give compounds 4a-p.
4-Amino-6-phenylpyrrolo[3,2- d ]pyrimidine (4a)
Yield 98%; mp 226-227 ˚C (from DMF-H2O). IR (KBr): νmax = 3444, 3441, 3396 (NH, NH2) cm. ¹H NMR (300 MHz, DMSO-d 6): δ = 6.81 (br s, 2 H, NH2), 6.86 (s, 1 H, C7H), 7.38 (t, J = 7.5 Hz, 1 H, ArH), 7.51 (t, J = 7.5 Hz, 2 H, ArH), 7.87 (d, J = 7.5 Hz, 2 H, ArH), 8.11 (s, 1 H, C2H), 11.64 (br s, 1 H, NH) ppm. ¹³C NMR (75 Hz, DMSO-d 6): δ = 98.6, 114.7, 125.1, 128.3, 129.0, 131.1, 131.4, 139.4, 150.2, 150.7 ppm. Anal. Calcd for C12H10N4: C, 68.56; H, 4.79; N, 26.65. Found: C, 68.37; H, 4.51; N, 26.88.
4-Amino-2-methylthio-6-phenylpyrrolo[3,2- d ]pyrimi-dine (4e)
Yield 82%; mp 235-237 ˚C (from DMF-H2O). IR (KBr): νmax = 3446, 3443, 3398 (NH, NH2) cm. ¹H NMR (300 MHz, DMSO-d 6): δ = 2.45 (s, 3 H, SCH3), 6.77 (s, 1 H, C7H), 7.14 (br s, 2 H, NH2), 7.36 (t, J = 7.5 Hz, 1 H, ArH), 7.49 (t, J = 7.5 Hz, 2 H, ArH), 7.91 (d, J = 7.5 Hz, 2 H, ArH), 12.19 (br s, 1 H, NH) ppm. ¹³C NMR (75 Hz, DMSO-d 6): δ = 13.4, 98.8, 112.9, 125.2, 127.4, 128.1, 131.5, 139.5, 148.8, 150.3, 160.6 ppm. Anal. Calcd for C13H12N4S: C, 60.91; H, 4.72; N, 21.86. Found: C, 60.77; H, 4.66; N, 21.99.
4-Morpholino-6-phenylpyrrolo[3,2- d ]pyrimidine (4p)
Yield 88%; mp >230 ˚C (dec.; from MeOH). IR (KBr): νmax = 3341 (NH) cm. ¹H NMR (300 MHz, CDCl3): δ = 3.87 (br s, 8 H, morpholino), 6.86 (s, 1 H, C7H), 7.41-7.48 (m, 3 H, ArH), 7.72 (d, J = 7.2 Hz, 2 H, ArH), 8.52 (s, 1 H, C2H), 9.23 (br s, 1 H, NH) ppm. ¹³C NMR (75 Hz, CDCl3): δ = 46.8, 66.6, 100.9, 116.4, 125.9, 129.1, 129.2, 131.2, 142.1, 150.8, 150.9, 151.4 ppm. Anal. Calcd for C16H16N4O: C, 68.55; H, 5.75; N, 19.99. Found: C, 68.50; H, 5.66; N, 20.08.

12

Compounds 4b-d,f-o and 5a were also fully characterized by IR, ¹H NMR, ¹³C NMR spectroscopic and microanalytical data.