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Synlett 2010(5): 721-724  
DOI: 10.1055/s-0029-1219385
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Direct Synthesis of N-Aryl Derivatives of Quinazolin-4(3H)-ones Employing Arylboronic Acids in the Presence of Cu(OAc)2

Kintali Sreeramamurthy, Ettam Ashok, Velisoju Mahendar, Gourishetti Santoshkumar, Parthasarathi Das*
Discovery Research, Dr. Reddy’s Laboratories Ltd., Bollaram Road, Miyapur, Hyderabad 500049, AP, India
Fax: +91(40)23045438; e-Mail: parthads@yahoo.com;
Further Information

Publication History

Received 7 September 2009
Publication Date:
10 February 2010 (online)

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Abstract

Copper-promoted N-arylation of quinazolin-4(3H)-ones with boronic acid at room temperature in the presence of air has been investigated. This method is general and can be applied to synthesizing derivatives of quinazolin-4(3H)-one with medicinal values.

Key words

Cu(OAc)2 - boronic acid - quinazolin-4(3H)-one

    References and Notes

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18

General Procedure for N-Arylation of 4 (3 H )-Quinazolinone
A mixture of the requisite 4 (3H)-quinazolinone (1.0 mmol), phenylboronic acid (1.5 mmol), anhyd Cu(OAc)2 (1.0 mmol) and Et3N (2.0 mmol) in dry CH2Cl2 (10-15 mL) was stirred at ambient temperature under air for 24-70 h. Progress of the reaction was monitored by TLC. The reaction mixture was filtered through Celite, the filtrate concentrated in vacuo, and the resulting mixture purified by chromatography on silica gel (CH2Cl2-MeOH) to yield the corresponding N-substituted quinazolin-4 (3H)-one.
Selected Spectroscopic DataTable 1, Entry 6
Brown solid; mp 221-223 ˚C. IR (KBr): 3105, 3043, 2976, 2495, 1928 1614 cm-1. ¹H NMR (400 MHz, DMSO-d 6): δ = 8.37 (s, 1 H), 8.14-8.12 (m, 1 H,), 7.95-7.93 (m, 1 H), 7.80-7.78 (m, 1 H), 7.62-7.60 (m, 2 H), 7.42-7.45 (m, 2 H). ¹³C NMR (50 MHz, CDCl3): δ = 159.0, 147.6, 146.4, 134.6, 131.6, 129.8, 129.6, 125.2, 116.2, 115.7. ESI-MS: 275 [M + H]+. ESI-HRMS: m/z calcd for C14H9ClFN2O [M + H]+: 275.0387; found: 275.0383.
Table 1, Entry 7
Brown solid; mp 194-196 ˚C. IR (KBr): 3066, 2981, 2939, 2727, 1681, 1556 cm-¹. ¹H NMR (400 MHz, DMSO-d 6): δ = 8.32 (s, 1 H), 8.17-8.15 (m, 1 H), 7.97-7.95 (m, 1 H) 7.76-7.73 (m, 1 H), 7.12-7.10 (m, 1 H), 7.03-6.98 (m, 2 H), 4.30 (s, 4 H). ¹³C NMR (50 MHz, CDCl3): δ = 159.0, 147.7, 146.3, 143.7, 143.2, 134.5, 131.4, 130.2, 129.4, 125.2, 123.1, 120.1, 117.0, 116.3, 64.0. ESI-MS: 315 [M + H]+. ESI-HRMS): m/z calcd for C16H12ClN2O3 [M + H]+: 315.0536; found: 315.0529.
Table 1, Entry 8
Brown solid; mp 190-192 ˚C. IR (KBr): 3086, 3026, 2962, 2654, 1739, 1610 cm-¹. ¹H NMR (400 MHz, DMSO-d 6): δ = 8.24 (s, 1 H), 7.58-7.48 (m, 6 H,), 7.20-7.18 (m, 1 H), 3.94 (s, 3 H), 3.89 (s, 3 H). ¹³C NMR (50 MHz, CDCl3): δ = 159.2, 154.6, 148.9, 145.6, 143.8, 137.7, 129.1, 128.5, 127.4, 114.8, 108.0, 105.4, 56.0, 55.7. ESI-MS: m/z = 283 [M + H]+. ESI-HRMS: m/z calcd for C16H15N2O3 [M + H]+: 283.1083; found: 283.1081.
Table 1, Entry 9
Brown solid; mp 243-245 ˚C. IR (KBr): 3433, 3060, 2962, 2837, 1683, 1610, 1502 cm-¹. ¹H NMR (400 MHz, DMSO-d 6): δ = 8.22 (s, 1 H), 7.49-7.47 (m, 1 H), 7.46-7.44 (m, 1 H), 7.39-7.37 (m, 2 H), 7.19-7.17 (m, 1 H), 3.94 (s, 3 H), 3.88 (s, 3 H), 2.30 (s, 3 H). ¹³C NMR (50 MHz, CDCl3): δ = 161.4, 159.2, 154.68, 148.99, 145.64, 143.84, 133.65, 130.68, 126.9, 125.3, 115.6, 114.7, 108.0, 105.3, 56.02, 55.75, 14.07. ESI-MS: m/z 315 [M + H]+. ESI-HRMS: m/z calcd for C17H16FN2O3 [M + H]+: 315.1145; found: 315.1143.

20

Selected Spectroscopic DataTable 2, Entry 2
Brown solid; mp 125-127 ˚C. IR (KBr): 3429, 3076, 2954, 2495, 2854 2445, 1678 cm-¹. ¹H NMR (400 MHz, DMSO-d 6): δ = 8.22 (s, 1 H), 7.60-7.58 (m, 2 H,), 7.56-7.54 (m, 1 H), 7.40-7.36 (m, 2 H), 7.20-7.18 (m, 1 H), 4.20-4.18 (m, 2 H), 3.85 (s, 3 H), 3.60-3.58 (m, 4 H), 2.46-2.38 (m, 6 H), 1.96-1.94 (m, 2 H). ¹³C NMR (50 MHz, CDCl3): δ = 164.0, 159.0, 153.9, 149.0, 145.5, 143.7,134.0, 133.8, 129.7, 129.5, 116.0, 115.6, 114.6, 108.6, 105.5, 66.9, 64.8, 55.7, 54.6, 53.0, 25.4. ESI-MS: 414 [M + H]+. ESI-HRMS: m/z calcd for C22H25FN3O4 [M + H]+: 414.1829; found: 414.1830.