Easy access for the synthesis of 2-aryl 2,3-dihydroquinazolin-4(1H)-ones using gem-dibromomethylarenes as synthetic aldehyde equivalent

Abstract

One step synthesis of 2,3-dihydroquinazolin-4(1H)-ones from gem-dibromomethylarenes using 2-aminobenzamide is described. Gem-dibromomethylarenes are used as aldehyde equivalent for the efficient synthesis of 2,3-dihydroquinazolin-4(1H)-ones, this synthesis takes shorter reaction time with quick isolation and excellent product yield.

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Introduction

Quinazolinone derivatives have drawn considerable attention due to their antidepressant,^1a analgesic,^1b diuretic,^1c antihistamine,^2a vasodilating,^2b antihypertensive,^2c and anti-inflammatory activities.³ They also possess anticancer⁴ activities like inhibition of tubulin formation,^5,6 inhibition against VEGFR2 tyrosine kinase and cell proliferation.⁷ These N-containing heterocyclic compounds are integral part of many drug molecules and several classical methods for the synthesis of 2,3-dihydroquinazoline-4(1H)-ones are available.^8–15

Many transition metals like Sc, Ti, Co, Cu, Zn, Zr, and Ru are used in the synthesis of 2,3-dihydroquinazoline-4(1H)-ones.^16a–g In addition, gem-dibromomethylarenes are used as aldehyde equivalent in the synthesis of cinnamic acids,^17a cinnamic esters,^17b benzimidazoles,^18a benzothiazoles^18b and aryl oximes.^18c In continuation of our studies^18a,b,c (Scheme 1), we tried using gem-dibromomethylarenes for the synthesis of 2,3-dihydroquinazoline-4(1H)-ones.

Scheme 1 Examples of gem-dibromomethylarenes as aldehyde equivalent in synthesis.

We investigated model reaction between 2-aminobenzamide and gem-dibromomethylarenes under different conditions, and the results are presented in Table 1.

Table 1 Optimization experiments for the synthesis of 3a^a

Entry	Base	Equivalent	Temp. (°C)	Time (h)	Yield^b (%) of 3a
a Reaction condition: gem-dibromomethylarenes 1 (1.0 equiv.) and 2-aminobenzamide 2 (1.1 equiv.), (t-BuOK) 1.0 mmol.b Isolated yields after column chromatography.
1	t-BuOK	0.5	0–25	6	Trace
2	t-BuOK	0.5	80	6	45
3	t-BuOK	1.0	80	4	90
4	t-BuOK	1.5	80	4	89
5	DIPEA	1.0	80	6	—
6	TEA	1.0	80	6	—
7	DABCO	1.0	80	6	—
8	DBU	1.0	80	6	—
9	Pyrrolidine	1.0	80	6	18
10	Morpholine	1.0	80	6	22
11	Piperidine	1.0	80	6	30

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Results and discussion

The synthesis of gem-dibromomethylarenes was initiated from the corresponding commercially available methyl analogues using N-bromo succinamide (2.0 equiv.) in carbon tetrachloride with a catalytic amount of benzoyl peroxide (0.2 equiv.) under reflux conditions. A mixture of 1-chloro-3-(dibromomethyl)benzene 1a (1.0 equiv), 2-aminobenzamide 2a (1.1 equiv.), potassium tert-butoxide (t-BuOK) (0.5 equiv.) in anhydrous pyridine and dimethylformamide (3 : 1 ratio) solvent was stirred at room temperature, but only trace amount of product was obtained even after 6 h of stirring (entry 1, Table 1). Improvement in product yield (entry 2, Table 1) was achieved when the reaction mixture was heated at 80 °C for 6 h. The reaction was monitored by increasing the equivalence of t-BuOK, and the maximum yield was obtained with 1.0 mmol of t-BuOK, and the starting material was consumed in 4 h as indicated by TLC. After workup and purification by column chromatography, 2-(3-chlorophenyl)-2,3-dihydroquinazolin-4(1H)-one 3a was isolated with 90% yield (entries 3 and 4, Table 1), and any increase in the equivalent of base did not influence the yield. Bases, like N-ethyldiisopropylamine, triethylamine, DABCO and DBU, did not promote the reaction (entries 5–8, Table 1), whereas pyrrolidine, morpholine and piperidine gave less yields in 6 h (entries 9–11, Table 1). Both aromatic and heteroaromatic gem-dibromomethylarenes bearing various functionalities, such as chloro, bromo, fluoro, methoxy, ester, tert-butyl and trifluoro methyl, –OTHP, –OTBDMS groups, survived the reaction and provided high yields of corresponding products (Table 2). The reaction of gem-dibromomethylarenes with 2-aminobenzamide yielded corresponding 2,3-dihydroquinazolin-4(1H)-ones, and the proposed reaction mechanism is shown in Scheme 2.

Table 2 2-Aryl-2,3-dihydro quinazolin-4(1H)-ones results

Entry	(Ar) substrate^a (1)	Yield (1) (%)	(2)	Product (3)	Time (h)	Yield (3)^b^,^c (%)
a Substrates are prepared from the commercial methyl analogues by radical bromination.b Isolated yields of product (3).c Literature reported compounds.
1		87	R = –H, R^1 = –H, 2a		4	90^11
2		84	R = –H, R^1 = –H, 2a		4	88^15
3		78	R = –H, R^1 = –H, 2a		4.5	84^8
4		80	R = –H, R^1 = –H, 2a		4	86^9
5		81	R = –H, R^1 = –H, 2a		4	78
6		86	R = Cl, R^1 = –H, 2b		4	85
7		84	R = Cl, R^1 = –H, 2b		4	86
8		87	R = OMe, R^1 = OMe, 2c		4	90
9	1g	—	R = OMe, R^1 = OMe, 2c		4	81
10		77	R = –H, R^1 = Cl, 2d		4	78
11	1e	—	R = –H, R^1 = Cl 2d		4	83
12		80	R = –H, R^1 = Cl, 2d		4	79
13	1f	—	R = –H, R^1 = Cl, 2d		4	85
14		85	R = –H, R^1 = Br, 2e		4	88
15	1i	—	R = –H, R^1 = Br, 2e		4	89
16		45	R = –H, R^1 = –H, 2a		4	60
17		84	R = –H, R^1 = –H, 2a		4	75

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Scheme 2 Proposed mechanism of reaction between gem-dibromomethylarene and 2-aminobenzamide in pyridine/dimethyl formamide.

Conclusion

In summary, this is an effective and efficient method of conversion of substituted 2-aminobenzamide into corresponding 2,3-dihydroquinazolin-4(1H)-ones using gem-dibromomethylarenes under mild reaction conditions. The use of gem-dibromomethylarenes for the direct synthesis of biologically important 2,3-dihydroquinazolin-4(1H)-ones has been indicated. As this reaction provides 2,3-dihydroquinazolin-4(1H)-ones in a single step from gem-dibromomethylarenes, it is one of the easiest pathways for accessing these compounds and the starting material is easily available. This transformation would have many applications in synthetic chemistry.

Experimental section

General information

Melting points were recorded (uncorrected) on a Buchi Melting Point B-545 instrument. Infrared (IR) spectra were recorded using a Jasco FTIR-4100 series. All reagents and solvents used were commercially procured and used as received. The ¹H NMR spectra were measured on a Bruker DPX-400 at 400 MHz with TMS as internal standard. The ¹³C NMR spectra were measured on a Bruker DPX-400 at 100 MHz. The mass spectra were recorded on a JEOL JMS-AX505HA mass spectrometer.

Typical procedure for the synthesis of 2-(4-tert-butylphenyl)-6-chloro-2,3-dihydroquinazolin-4(1H)-one (3f). Potassium tert-butoxide (0.366 g, 0.00327 mol) was added to a suspension of 4-tertiary butylbenzalbromide (1f) (1 g, 0.00327 mol) and 2-amino-5-chlorobenzamide (2b) (0.614 g, 0.0036 mol) in pyridine–dimethyl formamide (6.0 : 2.0 mL) solvent mixture. The resultant mixture was heated at 80 °C for 4 h. Progress of the reaction was monitored by TLC. The reaction mass was mixed with water then extracted with ethyl acetate (2 × 20 mL), and the organic phase was washed with brine solution and dried over anhydrous sodium sulphate. The organic phase was evaporated and the crude product was purified by column chromatography using silica gel mesh 100–200 (30% EtOAc in hexane).

2-(3-Chlorophenyl)-2,3-dihydroquinazolin-4(1H)-one (3a). White solid; m.p. 188.9–189.9 °C. (Lit.¹¹ 189.8–189.9 °C) IR (KBr) ν_max 3290, 3199, 1652, 1613 cm⁻¹. ¹H NMR (400 MHz, DMSO-d₆): δ 8.42 (s, 1H), 7.63–7.60 (m, 1H), 7.53 (s, 1H), 7.47–7.31 (m, 3H), 7.23–7.27 (m, 2H), 6.77 (d, J = 7.6 Hz, 1H), 6.69 (t, J = 7.6 Hz, 1H), 5.77 (s, 1H) ppm; ¹³C NMR (100 MHz, DMSO-d₆): δ 163.9, 147.9, 144.8, 133.9, 133.4, 130.7, 128.7, 127.8, 127.2, 125.8, 117.8, 115.3, 114.9, 66.0 ppm; MS(ESI): m/z = 258.8, HRMS (ESI): calcd for [C₁₄H₁₃ClN₂O + H⁺]: 259.7109, found 259.7105.

2,4-Dichloro, 3-dihydroquinazolin-4(1H)-one (3b). White solid, m.p. 182–184 °C (Lit.¹⁵ 181–185 °C); IR (KBr): 3337, 3179, 3025, 1661 cm⁻¹. ¹H NMR (DMSO-d₆, 400 MHz): 8.25 (s, 1H), 7.68–7.65 (m, 3H), 7.50–7.47 (m, 1H), 7.29–7.24 (t, J = 7.5 Hz, 1H), 7.04 (s, 1H), 6.93 (d, J = 6.4 Hz, 1H), 6.71 (t, J = 8.1 Hz, 1H), 6.1 (s, 1H) ppm; ¹³C NMR (100 MHz DMSO-d₆): δ 163.6, 147.5, 136.9, 133.9, 133.5, 132.9, 130.9, 128.9, 128.6, 127.4, 117.6, 114.7, 114.6, 63.3 ppm; MS(ESI): m/z = 293.148, HRMS (ESI): calcd for [C₁₄H₁₁Cl₂N₂O + H⁺]: 294.1559, found 294.1556.

2-(Pyridin-4-yl)-2,3-dihydroquinazolin-4(1H)-one (3c). Light yellow solid; m.p.: 187–188 °C (lit.⁸ not reported) IR (KBr): 2922, 2853, 1674, 1605, cm⁻¹. ¹H NMR (400 MHz, DMSO-d₆): δ = 8.88 (d, 2H, J = 6.0 Hz), 8.36 (d, 2H, J = 7.5 Hz), 8.17 (d, 2H, J = 4.5 Hz), 7.88 (d, 2H, J = 3.0 Hz), 7.63–7.58 (m, 1H), 5.85 (s, 1H), 5.04 (s, 1H) ppm; ¹³C NMR (100 MHz, DMSO-d₆): δ = 160.93, 147.98, 146.88, 132.95, 126.34, 125.84, 124.46, 120.22, 69.15 ppm; MS(ESI): m/z = 225.245. HRMS (ESI): calcd for [C₁₃H₁₂N₃O + H⁺]: 226.2539. Found 226.2535.

Methyl 4-(4-oxo-1,2,3,4-tetrahydroquinazolin-2-yl)benzoate (3d). White solid; m.p.: 200.2–202.4; (lit.⁹ 199.2–202.3 °C). IR (KBr): 3328, 3025, 2930, 1760, 1610 cm⁻¹. ¹H NMR (400 MHz, DMSO-d₆): δ 8.40 (s, 1H), 7.97 (d, J = 8.3 Hz, 2H), 7.64–7.57 (m, 3H), 7.28–7.22 (m, 2H), 6.75 (d, J = 7.5 Hz 1H), 6.68 (td, J = 7.5, 1.0 Hz, 1H), 5.84 (t, J = 2.1 Hz, 1H), 3.85 (s, 3H) ppm; ¹³C NMR (100 MHz, DMSO-d₆): δ 165.91, 163.36, 147.50, 146.94, 133.40, 129.56, 129.22, 129.22, 127.33, 127.14, 127.14, 117.26, 114.86, 114.43, 65.88, 52.16 ppm; MS(ESI): m/z = 282.294, HRMS (ESI) calcd for [C₁₆H₁₅N₂O₃ + H⁺]: 283.3019, found 283.3015.

2-(5-Phenylpyridin-2-yl)-2,3-dihydroquinazolin-4(1H)-one (3e). Light yellow solid; m.p.: 185–186 °C; IR (KBr) ν_max 3184.26, 3066.61, 2929.67, 1666.38, 1610.45 cm⁻¹. ¹H NMR (400 MHz, DMSO-d₆): δ 8.66–8.64 (d, J = 4.8 Hz, 1H), 8.32 (s 1H), 8.09–8.07 (d, J = 8.4 Hz, 2H), 7.95–7.93 (d, J = 8 Hz, 1H), 7.88–7.84 (tt, J = 1.6 Hz, 1H), 7.62–7.58 (m 3H), 7.35–7.32 (m, 1H), 7.26–7.22 (tt, J = 8.4 Hz, 1H), 7.15 (s, 1H), 6.76–6.74 (d, J = 8 Hz, 1H), 6.69–6.52 (tt, J = 8 Hz, 1H), 5.8 (s, 1H) ppm; ¹³C NMR (100 MHz, DMSO-d₆): δ 163.52, 155.57, 149.54, 147.76, 142.41, 138.8, 137.2, 133.3, 127.34, 127.22, 126.45, 122.68, 120.29, 117.13, 114.97, 114.42, 66.18 ppm; MS(ESI): m/z = 301.122, HRMS (ESI) calcd for [C₁₉H₁₅N₃O + H⁺] 302.3498, found 302.3495.

2-(4-tert-Butylphenyl)-6-chloro-2,3-dihydroquinazolin-4(1H)-one (3f). Light yellow solid; m.p.: 180–182 °C; IR (KBr) ν_max 3328.91, 3257.55, 2929.67, 1741.60, 1612.38 cm⁻¹.¹H NMR (400 MHz, DMSO-d₆): δ 8.38 (s, 1H), 7.53–7.52 (d, J = 2.4 Hz, 1H), 7.42–7.38 (m, 4H), 7.27–7.24 (m, 2H), 6.75–6.73 (d, J = 8.4 Hz, 1H), 5.73 (s, 1H), 1.26 (S, 9H) ppm; ¹³C NMR (100 MHz, DMSO-d₆): δ 162.40, 151.13, 146.62, 138.18, 132.96, 126.59, 126.35, 126.20, 125.11, 120.61, 116.31, 116, 66.27, 34.28, 31.04 ppm; MS(ESI): m/z = 314.119. HRMS (ESI) calcd for [C₁₈H₂₀ClN₂O + H⁺] 315.8172 found 315.8170.

6-Chloro-2-(3,4,5-trimethoxyphenyl)-2,3-dihydroquinazolin-4(1H)-one (3g). White solid; m.p.: 158–160 °C. IR (KBr) ν_max 3274.90, 3197.76, 2964.39, 2929.67, 1654, 1612.33 cm⁻¹. ¹H NMR (400 MHz, DMSO-d₆): δ 8.36 (s, 1H), 7.54–7.53 (d, J = 2.4 Hz, 1H), 7.29–7.24 (m, 2H), 6.82–6.77 (m, 4H), 5.72 (S, 1H), 3.76 (s, 6H), 3.64 (s, 3H) ppm; ¹³C NMR (100 MHz, DMSO-d₆): δ 162.49, 152.76, 146.73, 137.69, 136.17, 133.02, 126.40, 120.86, 116.42, 116.12, 104.45, 66.73, 59.95, 59.71, 55.92 ppm; MS(ESI): m/z = 348.088, HRMS (ESI) calcd for [C₁₇H₁₈ClN₂O₄ + H⁺] 349.7888, found 349.7885.

6,7-Dimethoxy-2-(4-(trifluoromethyl)phenyl)-2,3-dihydroquinazolin-4(1H)-one (3h). Light yellow solid; m.p.: 188–189 °C; IR (KBr) ν_max 3301.91, 3197.76, 2925.81, 2852.52, 1649.02, 1618.17 cm⁻¹; ¹H NMR (400 MHz, DMSO-d₆): δ 8.18 (s, 1H), 7.75–7.67 (m, 4H), 7.08 (s, 1H), 6.91 (s, 1H), 6.35 (s, 1H), 5.77 (s, 1H), 3.72 (s, 3H), 3.65 (S, 3H) ppm; ¹³C NMR (100 MHz, DMSO-d₆): δ 163.44, 153.93, 146.60, 143.07, 141.58, 127.74, 127.54, 125.18, 125.15, 125.04, 109.74, 106.62, 97.99, 65.92, 55.74, 55.34 ppm; MS(ESI): m/z = 352.307, HRMS (ESI) calcd for [C₁₇H₁₆F₃N₂O₃ + H⁺] 353.3157, found 353.3155.

6,7-Dimethoxy-2-(3,4,5-trimethoxyphenyl)-2,3-dihydroquinazolin-4(1H)-one (3i). Light red solid; m.p.: 242–244 °C. IR (KBr) ν_max 3353.98, 3197.76, 2937.38, 2837.09, 1654.81, 1620.09, cm⁻¹. ¹H NMR (400 MHz, DMSO-d₆): δ 7.49 (s, 1H), 7.13 (s, 1H), 6.85 (s, 2H), 6.7 (s, 1H), 6.4 (s, 1H), 5.64 (s, 1H), 3.78 (s, 3H) ppm; ¹³C NMR (100 MHz, DMSO-d₆): δ 163.82, 153.78, 152.83, 152.64, 143.75, 141.55, 137.48, 136.52, 109.79, 108.24, 104.96, 104.80, 97.99, 67.30, 59.91, 55.87, 55.77, 55.69, 55.35 ppm; MS(ESI): m/z = 374.387, HRMS (ESI) calcd for [C₁₉H₂₃N₂O₆ + H⁺] 375.3957, found 375.3954.

2-(2-Bromo-5-chlorophenyl)-7-chloro-2,3-dihydroquinazolin-4(1H)-one (3j). White solid; m.p.: 197–198 °C; IR (KBr) ν_max 3353.98, 3288.4, 3182.33, 3051.18, 2921.96, 2854.45, 1694.02, 1610.45 cm⁻¹; ¹H NMR (400 MHz, DMSO-d₆): δ 8.33 (s, 1H), 7.74–7.7 (m, 1H), 7.63 (s, 1H), 7.41–7.38 (dd, J = 2.6 Hz, 1H), 7.29–7.22 (m, 2H), 6.81–6.8 (d, J = 1.2 Hz, 1H), 6.75–6.72 (dd, J = 1.8 Hz, 1H), 6.1 (s, 1H) ppm; ¹³C NMR (100 MHz, DMSO-d₆): δ 162.57, 160.13, 148.35, 141.02, 138.01, 134.65, 129.35, 117.92, 117.6, 116.58, 115.99, 115.75, 113.27, 66.24 ppm; MS(ESI): m/z = 355.589, HRMS(ESI) calcd for [C₁₄H₁₀BrClFN₂O + H⁺] 356.5974, found 356.5971.

7-Chloro-2-(5-phenylpyridin-2-yl)-2,3-dihydroquinazolin-4(1H)-one (3k). Brown solid; m.p.: 208–210 °C; IR (KBr) ν_max 3193.9, 3068.53, 2923.88, 2854.45, 2813.95, 1666.38, 1610.45 cm⁻¹; ¹H NMR (400 MHz, DMSO-d₆): δ 8.66–8.65 (d, J = 4.4 Hz, 1H), 8.45 (s, 1H), 8.11–8.09 (d, J = 8.4 Hz, 1H), 7.95–7.93 (d, J = 8 Hz, 1H), 7.89–7.84 (tt, J = 1.46 Hz, 1H), 7.62–7.56 (m, 4H), 7.43 (s, 1H), 7.36–7.33 (m, 1H), 6.8–6.79 (d, J = 2 Hz, 1H), 6.69–6.67 (dd, J = 2 Hz, 1H), 5.86 (s, 1H) ppm; ¹³C NMR (100 MHz, DMSO-d₆): δ 162.63, 155.48, 149.53, 148.66, 142.04, 138.94, 137.81, 137.37, 137.21, 129.32, 128.35, 127.1, 126.54, 122.69, 120.29, 117.04, 113.62, 113.42, 66.07 ppm; MS(ESI): m/z = 335.787, HRMS (ESI) calcd for [C₁₉H₁₅ClN₃O + H⁺] 336.7949, found 336.7945.

7-Chloro-2-(2,5-dimethoxyphenyl)-2,3-dihydroquinazolin-4(1H)-one (3l). Light yellow solid; m.p.: 208–210 °C; IR (KBr) ν_max 3330.84, 3298.05, 3234.4, 3060.82, 2962.46, 2867.95, 1643.24, 1610.45 cm⁻¹; ¹H NMR (400 MHz, DMSO-d₆): δ 8.11 (s, 1H), 7.61–7.59 (d, J = 8.4 Hz, 1H), 7.04 (s, 1H), 6.99–6.96 (m, 1H), 6.9–6.87 (m, 2H), 6.817–6.813 (d, J = 1.6 Hz, 1H), 6.67–6.65 (dd, J = 2 Hz, 1H), 5.99 (s, 1H), 3.77 (s, 3H), 3.66 (s, 3H) ppm; ¹³C NMR (100 MHz, DMSO-d₆): δ 162.91, 152.85, 150.36, 148.71, 137.74, 129.58, 129.21, 124.74, 116.92, 113.61, 113.5, 113.34, 112.24, 61.07, 55.99, 55.36 ppm; MS(ESI): m/z = 318.754. HRMS (ESI) calcd for [C₁₆H₁₆ClN₂O₃+H⁺] 319.7628, found 319.7628.

2-(4-tert-Butylphenyl)-7-chloro-2,3-dihydroquinazolin-4(1H)-one (3m). Light yellow solid; m.p.: 110–112 °C; IR (KBr) ν_max 3332.76, 3170.76, 3031.89, 2925.81, 2831.31, 1656.74, 1608.52 cm⁻¹; ¹H NMR (400 MHz, DMSO-d₆): δ 8.31 (s, 1H), 8.14–8.1 (dd, J = 2.6 Hz, 1H), 7.6–7.38 (m, 4H), 7.3 (s, 1H), 6.757–6.752 (d, J = 2 Hz, 1H), 6.67–6.65 (dd, J = 2 Hz, 1H), 5.75 (s, 1H) ppm; ¹³C NMR (100 MHz, DMSO-d₆): δ 162.71, 151.17, 148.8, 138.24, 137.72, 129.13, 127.68, 126.55, 125.43, 125.3, 116.9, 113.6, 113.31, 66.33, 34.29, 31.04, 30.84 ppm; MS(ESI): m/z = 314.809, HRMS (ESI) calcd for [C₁₈H₂₀ClN₂O + H⁺] 315.8172, found 315.8170.

7-Bromo-2-(3,4-dimethoxyphenyl)-2,3-dihydroquinazolin-4(1H)-one (3n). White solid; m.p.: 137–138 °C; IR (KBr) ν_max 3298.26, 3182.33, 3070.46, 2956.67, 2923.67, 2923.88, 2852.52, 1700, 1610 cm⁻¹; ¹H NMR (400 MHz, DMSO-d₆): δ 8.38 (s, 1H), 7.52–7.49 (m, 3H), 7.33 (s, 1H), 7.24–7.2 (m, 1H), 6.94–6.93 (d, J = 2 Hz, 1H), 6.83–6.80 (dd, J = 1.8 Hz, 1H), 5.81 (s, 1H), 3.68 (s, 6H) ppm; ¹³C NMR (100 MHz, DMSO-d₆): δ 162.65, 148.42, 141.06, 134.75, 129.42, 127, 120.44, 118.16, 117.94, 116.63, 115.98, 115.74, 113.57, 66.20, 55.42, 55.36 ppm; MS(ESI): m/z = 363.205, HRMS (ESI) calcd for [C₁₆H₁₆BrN₂O₃+H⁺] 364.2138, found 364.2135.

7-Bromo-2-(2-bromo-5-fluorophenyl)-2,3-dihydroquinazolin-4(1H)-one (3o). White solid; m.p.: 206–207 °C; IR (KBr) ν_max 3294.36, 3194.33, 3074.5, 2958.67, 2926.86, 2854.53, 1705.1, 1605 cm⁻¹; ¹H NMR (400 MHz, DMSO-d₆): δ 8.34 (s, 1H), 7.74–7.7 (m, 1H), 7.57–7.55 (d, J = 8.4 Hz, 1H), 7.40–7.37 (dd, J = 3.2 Hz, 1H),7.28–7.23 (m, 2H), 6.963–6.960 (d, J = 1.2 Hz, 1H), 6.89–6.86 (dd, J = 1.8 Hz, 1H), 6.09 (s, 1H) ppm; ¹³C NMR (100 MHz, DMSO-d₆): δ 162.69, 160.91, 148.74, 137.49, 129.39, 128.95, 126.82, 125.16, 119.96, 116.40, 115.28, 115.07, 113.88, 65.75 ppm; MS (ESI): m/z = 400.04, HRMS (ESI) calcd for [C₁₄H₁₀Br₂FN₂O + H⁺] 401.0484, found 401.0481.

2-(4-(Tetrahydro-2H-pyran-2-yloxy)phenyl)-2,3-dihydroquinazolin-4(1H)-one (3p). White solid; m.p.: 136–138 °C; IR (KBr) ν_max 3327, 3028, 2932, 1738, 1615 cm⁻¹; ¹H NMR (400 MHz, DMSO-d₆): δ 8.16 (s, 1H), 7.59–7.57 (d, J = 8 Hz, 1H), 7.39–7.37 (d, J = 8 Hz, 2H), 7.23–7.19 (t, J = 7.6 Hz, 1H), 7.02–6.98 (m, 3H), 6.72–6.63 (m, 2H) 5.67 (s, 1H), 5.45 (s, 1H), 3.72–3.67 (m, 1H), 3.52–3.48 (m, 1H), 1.88–1.69 (m, 3H), 1.60–1.48 (m, 4H) ppm; ¹³C NMR (100 MHz, DMSO-d₆): 164.13, 157.07, 148.43, 134.88, 134.86, 133.69, 128.54, 127.78, 117.52, 116.63, 115.39, 114.83, 96.04, 66.79, 61.91, 30.21, 25.11, 18.98 ppm; MS (ESI): 324.14, HRMS (ESI) calcd for [C₁₉H₂₀N₂O₃+H⁺] 325.1552, found 325.1550.

2-(4-(tert-Butyldimethylsilyloxy)phenyl)-2,3-dihydroquinazolin-4(1H)-one (3q). White solid; m.p.: 139–141 °C; IR (KBr) ν_max 3329.86, 3032.60, 2928.72, 1740.30, 1612.30 cm⁻¹; ¹H NMR (400 MHz, DMSO-d₆): δ 8.17 (s, 1H), 7.64–7.62 (dd, J = 1.6 Hz, 1H), 7.41–7.39 (dd, J = 2 Hz, 2H), 7.28–7.24 (m, IH), 7.02 (s, 1H), 6.89–6.87 (dd, J = 2 Hz, 2H), 6.77–6.75 (d, J = 8.4 Hz, 1H) 6.71–6.67 (m, 1H), 5.72 (s, 1H), 1.02–0.92 (m, 9H), 0.25–0.15 (m, 6H) ppm; ¹³C NMR (100 MHz, DMSO-d₆): 164.07, 155.77, 148.45, 134.8, 133.69, 128.78, 127.77, 119.97, 117.50, 115.32, 114.81, 66.85, 26.0, 18.38, −4.08 ppm; MS (ESI): 354.17, HRMS (ESI) calcd for [C₂₀H₂₆N₂O₂Si + H⁺] 355.1852, found 358.1948.

Acknowledgements

KHN is grateful to UGC, RFSMS Govt. of India for financial support, KSR is grateful to DST, CSIR, for the financial assistance under different projects: no. DST/INT/SA/P-05/2011-12, dated 10-01-12; INT/Indo-Korea/122/2011-12, dated 13.09.2011. no. 01 (2434)/10/EMR-II, dated 28.12.2010; IFCPAR Sanction no. IFC/4303-1/2010-11 dated 22/12/2010.

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Footnote

† Electronic supplementary information (ESI) available. See DOI: 10.1039/c4ra02312a

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