PAPER
Dihydroquinazolinones through Palladium-Catalyzed Intramolecular Arylation of Ureas
1385
Stark apparatus until azeotropic removal of water was complete.
The solvent was removed and the slight excess of benzylamine was
eliminated under high vacuum. The crude residue was dissolved in
anhyd MeOH (8 mL) and NaBH4 (102 mg, 2.7 mmol) was added
portionwise. The mixture was stirred at r. t. overnight. MeOH was
removed under reduced pressure, EtOAc (30 mL) and H2O (15 mL)
were added to the residue. The phases were separated and the organ-
ic layer was washed with H2O (2 × 10 mL), dried (Na2SO4) and
evaporated under vacuum to give 1a,b as oils. They were used with-
out any further purification.
3-Benzyl-1-phenyl-3,4-dihydroquinazolin-2(1H)-one
(3, R1 = Ph)
Mp 98–99 °C.
IR (Nujol): 1667, 1606 cm–1.
1H NMR (300 MHz, CDCl3): = 4.45 (s, 2 H), 4.73 (s, 2 H), 6.24
(d, J = 8.1 Hz, 1 H), 6.83–6.88 (m, 1 H), 6.94–6.99 (m, 2 H), 7.30–
7.46 (m, 8 H), 7.50–7.56 (m, 2 H).
13C NMR (75 MHz, CDCl3): = 47.7, 51.4, 114.8, 118.9, 121.9,
125.5, 127.5, 127.7, 128.0, 128.3, 128.6, 129.7, 129.9, 136.8, 138.5,
140.3, 154.1.
N-Benzyl-N-(2-bromo-5-methoxybenzyl)amine (1a)
Yield: 66%.
MS (EI): m/z (%) = 314 (M+,40), 223 (55), 180 (100), 91 (40).
Anal. Calcd for C21H18N2O: C, 80.23; H, 5.77; N, 8.91. Found: C,
80.17; H, 5.79; N, 8.92.
IR (neat): 3342 cm–1.
1H NMR (CDCl3, 300 MHz): = 1.95 (br s, 1 H), 3.73 (s, 3 H), 3.75
(s, 2 H), 3.79 (s, 2 H), 6.64 (dd, J = 8.7, 3.1 Hz, 1 H), 6.96 (d,
J = 3.1 Hz, 1 H), 7.20–7.39 (m, 6 H).
3-Benzyl-1-(4-chlorophenyl)-3,4-dihydroquinazolin-2(1H)-one
(3, R1 = p-ClC6H4)
13C NMR (CDCl3, 75 MHz): = 53.0, 53.2, 55.4, 114.1, 115.8,
126.9, 128.1, 133.2, 140.1, 140.2, 159.0.
Mp 149–150 °C.
IR (Nujol): 1659, 1604 cm–1.
MS (EI): m/z (%) = 306 (M+, 18), 226 (56), 200 (47), 121 (49), 106
(82), 91 (100).
1H NMR (300 MHz, CDCl3): = 4.40 (s, 2 H), 4.72 (s, 2 H), 6.25
(d, J = 8.0 Hz, 1 H), 6.90 (t, J = 7.1 Hz, 1 H), 7.00–7.10 (m, 2 H),
7.20–7.40 (m, 7 H), 7.47 (d, J = 8.6 Hz, 2 H).
13C NMR (75 MHz, CDCl3): = 47.7, 51.4, 114.7, 119.0, 122.2,
125.6, 127.6, 127.8, 128.3, 128.6, 129.9, 131.3, 138.8, 136.6, 137.0,
140.0, 153.9.
N-Benzyl-N-[(2-bromopyridin-3-yl)methyl]amine (1b)
Yield: 77%.
IR (neat): 3305 cm–1.
1H NMR (CDCl3, 300 MHz): = 1.86 (br s, 1 H), 3.82 (s, 2 H), 3.86
(s, 2 H), 7.20–7.35 (m, 6 H), 7.76 (dd, J = 7.5, 1.7 Hz, 1 H), 8.26
(dd, J = 4.7, 1.8 Hz, 1 H).
13C NMR (CDCl3, 75 MHz): = 51.9, 53.2, 122.8, 127.2, 128.1,
128.5, 136.6, 138.1, 139.7, 143.6, 148.4.
MS (EI): m/z (%) = 277 (M+, 38), 185 (57), 170 (36), 120 (23), 91
(100).
MS (EI): m/z (%) = 348 (M+, 20), 257 (40), 180 (100), 91 (35).
Anal. Calcd for C21H17ClN2O: C, 72.31; H, 4.91; N, 8.03. Found: C,
72.24; H, 5.00; N, 7.90.
4-(3-Benzyl-2-oxo-3,4-dihydroquinazolin-1(2H)-yl)benzoni-
trile (3, R1 = p-CNC6H4)
Mp 150–151 °C.
IR (Nujol): 2231, 1660, 1596 cm–1.
1H NMR (300 MHz, CDCl3): = 4.45 (s, 2 H), 4.72 (s, 2 H), 6.19
(d, J = 8.0 Hz, 1 H), 6.95–7.02 (m, 1 H), 7.06–7.11 (m, 2 H), 7.30–
7.41 (m, 5 H), 7.53 (d, J = 8.5 Hz, 2 H), 7.83 (d, J = 8.5 Hz, 2 H).
13C NMR (75 MHz, CDCl3): = 47.7, 51.4, 111.7, 114.6, 118.3,
119.3, 122.7, 125.8, 127.7, 128.0, 128.3, 128.7, 131.0, 133.4, 136.3,
139.4, 142.8, 153.4.
Compounds 3–3b; General Procedure
A Schlenk-type flask was charged under nitrogen with Pd(Ph3P)4
(23.1 mg, 0.02 mmol), anhyd K2CO3 (55.3 mg, 0.4 mmol), the bro-
moamine (0.2 mmol), anhyd toluene (2.5 mL). The resulting mix-
ture was cooled to 0 °C and the isocyanate (0.22 mmol) in anhyd
toluene (1.5 mL) was added. The mixture was heated under stirring
at 70 °C for 1 h, then at the temperature and for the time reported in
Table 1. After cooling to r.t., H2O (7 mL) was added and the reac-
tion mixture was extracted with EtOAc (3 × 5 mL). The combined
organic phases were dried (Na2SO4) and evaporated under vacuum.
The residue was purified by flash chromatography (silica gel; PE–
EtOAc). Compound 3 (R1 = Bu) was purified by column chroma-
tography on Florisil. Analytically pure samples of crystalline com-
pounds were obtained by recrystallization (hexane–EtOAc).
MS (EI): m/z (%) = 339 (M+, 25), 248 (80), 205 (100), 91 (65).
Anal. Calcd for C22H17N3O: C, 77.86; H, 5.05; N, 12.38. Found: C,
77.89; H, 5.13; N, 12.45.
3-Benzyl-6-methoxy-1-phenyl-3,4-dihydroquinazolin-2(1H)-
one (3a)
Mp 99 °C.
3-Benzyl-1-butyl-3,4-dihydroquinazolin-2(1H)-one (3, R1 = Bu)
Oil.
IR (neat): 2958, 2931, 2872, 1658, 1605 cm–1.
1H NMR (300 MHz, CDCl3): = 0.99 (t, J = 7.3 Hz, 3 H), 1.44 (sex,
J = 7.5 Hz, 2 H), 1.65–1.75, (m, 2 H), 3.90 (pseudo t, J = 7.7 Hz, 2
H), 4.26 (s, 2 H), 4.67 (s, 2 H), 6.87–7.00 (m, 3 H), 7.18–7.35 (m, 6
H).
IR (Nujol): 1662, 1596 cm–1.
1H NMR (300 MHz, CDCl3): = 3.71 (s, 3 H), 4.38 (s, 2 H), 4.69
(s, 2 H), 6.13–6.16 (m, 1 H), 6.56–6.59 (m, 2 H), 7.29–7.42 (m, 8
H), 7.47–7.52 (m, 2 H).
13C NMR (75 MHz, CDCl3): = 47.9, 51.3, 55.6, 111.0, 113.0,
115.9, 120.0, 127.5, 127.9, 128.4, 128.6, 129.6, 129.9, 134.1, 136.9,
138.7, 154.1, 154.8.
13C NMR (75 MHz, CDCl3): = 13.9, 20.2, 29.4, 42.8, 47.6, 51.4,
112.9, 119.8, 121.4, 125.7, 127.4, 128.1, 128.6, 137.0, 138.4, 154.7.
MS (EI): m/z (%) = 344 (M+, 100), 253 (57), 210 (98), 91 (32), 43
(47).
MS (EI): m/z (%) = 294 (M+, 50), 251 (25), 203 (100), 147 (35), 132
(20), 91 (95).
Anal. Calcd for C22H20N2O2: C, 76.72; H, 5.85; N, 8.13. Found: C,
76.70; H, 5.75; N, 8.02.
Anal. Calcd for C19H22N2O: C, 77.52; H, 7.53; N, 9.52. Found: C,
77.33; H, 7.41; N, 9.49.
Synthesis 2003, No. 9, 1383–1386 ISSN 1234-567-89 © Thieme Stuttgart · New York